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51.
Fomes sclerodermeus produces manganese peroxidase (MnP) and laccase as part of its ligninolytic system. A Doehlert experimental design was applied in order to find the optimum conditions for MnP and laccase production. The factors studied were Cu2+, Mn2+ and asparagine. The present model and data analysis allowed us not only to define optimal media for production of both laccase and MnP, but also to show the combined effects between the factors. MnP was strongly influenced by Mn2+, which acts as an inducer. Under these conditions Cu2+ negatively affected MnP activity. At 13 days of growth 0.75 U ml–1 were produced in the optimized culture medium supplemented with 1 mM MnSO4 and 4 g l–1 asparagine. The laccase titer under optimized conditions reached maximum values at 16 days of growth: 13.5 U ml–1 in the presence of 0.2 mM CuSO4, 0.4 mM MnSO4 and 6 g l–1 asparagine. Mn2+ promoted production of both enzymes. There were important interactions among the nutrients evaluated, the most significant being those between Cu2+ and asparagine. 相似文献
52.
53.
Oxidative stress in diabetes-induced endothelial dysfunction involvement of nitric oxide and protein kinase C 总被引:3,自引:0,他引:3
Pricci F Leto G Amadio L Iacobini C Cordone S Catalano S Zicari A Sorcini M Di Mario U Pugliese G 《Free radical biology & medicine》2003,35(6):683-694
Reactive oxygen species (ROS) formation plays a major role in diabetes-induced endothelial dysfunction, though the molecular mechanism(s) involved and the contribution of nitric oxide (NO) are still unclear. This study using bovine retinal endothelial cells was aimed at assessing (i) the role of oxygen-dependent vs. NO-dependent oxidative stress in the endothelial cell permeability alterations induced by the diabetic milieu and (ii) whether protein kinase C (PKC) activation ultimately mediates these changes. Superoxide, lipid peroxide, and PKC activity were higher under high glucose (HG) vs. normal glucose throughout the 30 d period. Nitrite/nitrate and endothelial NO synthase levels increased at 1 d and decreased thereafter. Changes in monolayer permeability to 125I-BSA induced by 1 or 30 d incubation in HG or exposure to advanced glycosylation endproduct were reduced by treatment with antioxidants or PKC inhibitors, whereas NO blockade prevented only the effect of 1 d HG. HG-induced changes were mimicked by a PKC activator, a superoxide generating system, an NO and superoxide donor, or peroxynitrite (attenuated by PKC inhibition), but not a NO donor. The short-term effect of HG depends on a combined oxidative and nitrosative stress with peroxynitrite formation, whereas the long-term effect is related to ROS generation; in both cases, PKC ultimately mediates permeability changes. 相似文献
54.
Flavia Kazue Ibuki Alyne Simões Fernando Neves Nogueira 《Cell biochemistry and function》2010,28(6):503-508
Hyperglycemia induces overproduction of superoxide and it is related to diabetic complications. In this study, we analyzed the antioxidant enzymatic defense and the lipid peroxidation of rat salivary glands in six different periods of diabetic condition. Ninety‐six rats were divided into 12 groups: C7/14/21/28/45/60 (non‐diabetic animals) and D7/14/21/28/45/60 (diabetic animals). Diabetes was induced by streptozotocin and the rats were euthanized after 7, 14, 21, 28, 45, or 60 days. Their parotid (PA) and submandibular (SM) glands were removed soon after the sacrifice and the total protein and malondialdehyde (MDA) concentrations, as well as, the superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities were determined. Twenty‐one days after the diabetes induction, the SM glands showed an increase in SOD, CAT, and GPx activities, as well as, MDA concentration. Concerning the PA glands, an increase in the CAT activity and MDA content was observed throughout the observation period. The results suggest that diabetes can cause alterations on the salivary glands and that PA and SM glands react differently when exposed to diabetes condition. However, no impairment of antioxidant system was observed in the group whose diabetic condition had been induced 60 days earlier, herein named 60‐day group. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
55.
Flavia Biamonte Fabiana Zolea Andrea Bisognin Maddalena Di Sanzo Claudia Saccoman Domenica Scumaci Ilenia Aversa Mariafranca Panebianco Maria Concetta Faniello Stefania Bortoluzzi Giovanni Cuda Francesco Costanzo 《PloS one》2015,10(3)
In a previous study, we showed that the silencing of the heavy subunit (FHC) offerritin, the central iron storage molecule in the cell, is accompanied by a modification in global gene expression. In this work, we explored whether different FHC amounts might modulate miRNA expression levels in K562 cells and studied the impact of miRNAs in gene expression profile modifications. To this aim, we performed a miRNA-mRNA integrative analysis in K562 silenced for FHC (K562shFHC) comparing it with K562 transduced with scrambled RNA (K562shRNA). Four miRNAs, namely hsa-let-7g, hsa-let-7f, hsa-let-7i and hsa-miR-125b, were significantly up-regulated in silenced cells. The remarkable down-regulation of these miRNAs, following FHC expression rescue, supports a specific relation between FHC silencing and miRNA-modulation. The integration of target predictions with miRNA and gene expression profiles led to the identification of a regulatory network which includes the miRNAs up-regulated by FHC silencing, as well as91 down-regulated putative target genes. These genes were further classified in 9 networks; the highest scoring network, “Cell Death and Survival, Hematological System Development and Function, Hematopoiesis”, is composed by 18 focus molecules including RAF1 and ERK1/2. We confirmed that, following FHC silencing, ERK1/2 phosphorylation is severely impaired and that RAF1 mRNA is significantly down-regulated. Taken all together, our data indicate that, in our experimental model, FHC silencing may affect RAF1/pERK1/2 levels through the modulation of a specific set of miRNAs and add new insights in to the relationship among iron homeostasis and miRNAs. 相似文献
56.
Macrophage tumoricidal activity relies, mainly, on the release of Tumor Necrosis
Factor alpha (TNFα) and/or on reactive oxygen or nitrogen intermediates. In
the present work, we investigated the cytotoxic activity of resident peritoneal
macrophages against L929 fibrosarcoma cell line in vitro and
in vivo. Resident macrophages lysed L929 cells in a mechanism
independent of TNFα and cell-to-cell contact. The cytotoxic activity was
largely dependent on nitric oxide (NO) release since treatment with L-NAME (NOS
inhibitor) inhibited L929 cells killing. Macrophages from mice with targeted deletion
of inducible NO synthase (iNOS) together with L929 cells produced less NO and
displayed lower, but still significant, tumoricidal activity. Notably, NO production
and tumor lysis were abolished in co-cultures with macrophages deficient in
Interferon Regulatory Factor, IRF-1. Importantly, the in vitro
findings were reproduced in vivo as IRF-1 deficient animals
inoculated i.p with L929 cells were extremely susceptible to tumor growth and their
macrophages did not produce NO, while WT mice killed L929 tumor cells and their
macrophages produced high levels of NO. Our results indicate that IRF-1 is a master
regulator of bi-directional interaction between macrophages and tumor cells. Overall,
IRF-1 was essential for NO production by co-cultures and macrophage tumoricidal
activity in vitro as well as for the control of tumor growth
in vivo. 相似文献
57.
58.
Denis Mubiru Robert Byabasheija John Baptist Bwanika Joslyn Edelstein Meier Godfrey Magumba Flavia Mpanga Kaggwa Jackson Ojera Abusu Alex Chono Opio Charles Clarke Lodda Jaanki Patel Theresa Diaz 《PloS one》2015,10(8)
Objective
Evidence is limited on whether Integrated Community Case Management (iCCM) improves treatment coverage of the top causes of childhood mortality (acute respiratory illnesses (ARI), diarrhoea and malaria). The coverage impact of iCCM in Central Uganda was evaluated.Methods
Between July 2010 and December 2012 a pre-post quasi-experimental study in eight districts with iCCM was conducted; 3 districts without iCCM served as controls. A two-stage household cluster survey at baseline (n = 1036 and 1042) and end line (n = 3890 and 3844) was done in the intervention and comparison groups respectively. Changes in treatment coverage and timeliness were assessed using difference in differences analysis (DID). Mortality impact was modelled using the Lives Saved Tool.Findings
5,586 Village Health Team members delivered 1,907,746 treatments to children under age five. Use of oral rehydration solution (ORS) and zinc treatment of diarrhoea increased in the intervention area, while there was a decrease in the comparison area (DID = 22.9, p = 0.001). Due to national stock-outs of amoxicillin, there was a decrease in antibiotic treatment for ARI in both areas; however, the decrease was significantly greater in the comparison area (DID = 5.18; p<0.001). There was a greater increase in Artemisinin Combination Therapy treatment for fever in the intervention areas than in the comparison area but this was not significant (DID = 1.57, p = 0.105). In the intervention area, timeliness of treatments for fever and ARI increased significantly higher in the intervention area than in the comparison area (DID = 2.12, p = 0.029 and 7.95, p<0.001, respectively). An estimated 106 lives were saved in the intervention area while 611 lives were lost in the comparison area.Conclusion
iCCM significantly increased treatment coverage for diarrhoea and fever, mitigated the effect of national stock outs of amoxicillin on ARI treatment, improved timeliness of treatments for fever and ARI and saved lives. 相似文献59.
Hector Aguilar Vitorino Luca Mantovanelli Flavia Pinheiro Zanotto Breno Pannia Espósito 《PloS one》2015,10(4)
Iron metallodrugs comprise mineral supplements, anti-hypertensive agents and, more recently, magnetic nanomaterials, with both therapeutic and diagnostic roles. As biologically-active metal compounds, concern has been raised regarding the impact of these compounds when emitted to the environment and associated ecotoxicological effects for the fauna. In this work we assessed the relative stability of several iron compounds (supplements based on glucoheptonate, dextran or glycinate, as well as 3,5,5-trimethylhexanoyl (TMH) derivatives of ferrocene) against high affinity models of biological binding, calcein and aprotransferrin, via a fluorimetric method. Also, the redox-activity of each compound was determined in a physiologically relevant medium. Toxicity toward Artemia salina at different developmental stages was measured, as well as the amount of lipid peroxidation. Our results show that polymer-coated iron metallodrugs are stable, non-redox-active and non-toxic at the concentrations studied (up to 300 µM). However, TMH derivatives of ferrocene were less stable and more redox-active than the parent compound, and TMH-ferrocene displayed toxicity and lipid peroxidation to A. salina, unlike the other compounds. Our results indicate that iron metallodrugs based on polymer coating do not present direct toxicity at low levels of emission; however other iron species (eg. metallocenes), may be deleterious for aquatic organisms. We suggest that ecotoxicity depends more on metal speciation than on the total amount of metal present in the metallodrugs. Future studies with discarded metallodrugs should consider the chemical speciation of the metal present in the composition of the drug. 相似文献
60.
Mariapaola Marino Flavia Scuderi Daniela Samengo Giorgia Saltelli Maria Teresa Maiuri Chengyong Shen Lin Mei Mario Sabatelli Giovambattista Pani Giovanni Antonini Amelia Evoli Emanuela Bartoccioni 《PloS one》2015,10(8)