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321.
Fotini Kostopoulou Konstantinos N Malizos Ioanna Papathanasiou Aspasia Tsezou 《Arthritis research & therapy》2015,17(1)
IntroductionSeveral studies have shown that osteoarthritis (OA) is strongly associated with metabolism-related disorders, highlighting OA as the fifth component of the metabolic syndrome (MetS). On the basis of our previous findings on dysregulation of cholesterol homeostasis in OA, we were prompted to investigate whether microRNA-33a (miR-33a), one of the master regulators of cholesterol and fatty acid metabolism, plays a key role in OA pathogenesis.MethodsArticular cartilage samples were obtained from 14 patients with primary OA undergoing total knee replacement surgery. Normal cartilage was obtained from nine individuals undergoing fracture repair surgery. Bioinformatics analysis was used to identify miR-33a target genes. miR-33a and sterol regulatory element-binding protein 2 (SREBP-2) expression levels were investigated using real-time PCR, and their expression was also assessed after treatment with transforming growth factor-β1 (TGF-β1) in cultured chondrocytes. Akt phosphorylation after treatment with both TGF-β1 and miR-33a inhibitor or TGF-β1 and miR-33a mimic was assessed by Western blot analysis. Furthermore, we evaluated the effect of miR-33a mimic and miR-33a inhibitor on Smad7, a negative regulator of TGF-β signaling, on cholesterol efflux-related genes, ATP-binding cassette transporter A1 (ABCA1), apolipoprotein A1 (ApoA1) and liver X receptors (LXRα and LXRβ), as well as on matrix metalloproteinase-13 (MMP-13), using real-time PCR.ResultsWe found that the expression of miR-33a and its host gene SREBP-2 was significantly elevated in OA chondrocytes compared with normal chondrocytes. Treatment of cultured chondrocytes with TGF-β1 resulted in increased expression of both miR-33a and SREBP-2, as well as in rapid induction of Akt phosphorylation, whereas TGF-β-induced Akt phosphorylation was enhanced by miR-33a and suppressed by inhibition of miR-33a, as a possible consequence of Smad7 regulation by miR-33a. Moreover, treatment of normal chondrocytes with miR-33a resulted in significantly reduced ABCA1 and ApoA1 mRNA expression levels and significantly elevated MMP-13 expression levels, promoting the OA phenotype, whereas miR-33a’s suppressive effect was reversed using its inhibitor.ConclusionsOur findings suggest, for the first time to our knowledge, that miR-33a regulates cholesterol synthesis through the TGF-β1/Akt/SREBP-2 pathway, as well as cholesterol efflux-related genes ABCA1 and ApoA1, in OA chondrocytes, pointing to its identification as a novel target for ameliorating the OA phenotype. 相似文献
322.
Siskou IC Rekka EA Kourounakis AP Chrysselis MC Tsiakitzis K Kourounakis PN 《Bioorganic & medicinal chemistry》2007,15(2):951-961
Six novel ibuprofen derivatives and related structures, incorporating a proline moiety and designed for neurodegenerative disorders, are studied. They possess anti-inflammatory properties and three of them inhibited lipoxygenase. One compound was found to inhibit cyclooxygenase (COX)-2 production in spleenocytes from arthritic rats. The HS-containing compounds are potent antioxidants and one of them protected against glutathione loss after cerebral ischemia/reperfusion. They demonstrated lipid-lowering ability and seem to acquire low gastrointestinal toxicity. Acetylcholinesterase inhibitory activity, found in two of these compounds, may be an asset to their actions. 相似文献
323.
Effect of Processing and Storage Parameters on the Oxidative Deterioration of Oil-in-Water Emulsions
Charikleia P. Dimakou Sotirios N. Kiokias Ioanna V. Tsaprouni Vassiliki Oreopoulou 《Food biophysics》2007,2(1):38-45
The effect of storage temperature, pH, and homogenization pressure on the oxidative deterioration of Tween 20 and sodium caseinate
sunflower oil-in-water emulsions was studied by monitoring conjugated dienes (CD), lipid hydroperoxides (LH), and thiobarbituric
acid reactive substances (TBARs). CD increased linearly with storage time, and the rate constant was temperature dependent
according to the Arrhenius equation with an activation energy equal to 37.5 kJ mol−1. The increase in LH and TBARs with temperature (5–60°C) was in good agreement with CD variation. Tween-stabilized emulsions
oxidized faster as pH increased from 3 to 7, whereas a different behavior was observed in emulsions stabilized with sodium
caseinate or a mixture of both emulsifiers. A change of homogenization pressure (30–900 bars), reflecting variation of emulsion
average droplet size, had no effect on the oxidative stability of the emulsions. 相似文献
324.
325.
Constantine Garagounis Daniela Tsikou Panagiota K. Plitsi Ioanna S. Psarrakou Marianna Avramidou Catalina Stedel Maria Anagnostou Maria E. Georgopoulou Kalliope K. Papadopoulou 《The Plant journal : for cell and molecular biology》2019,98(2):228-242
Glycogen synthase kinase/SHAGGY‐like kinases (SKs) are a highly conserved family of signaling proteins that participate in many developmental, cell‐differentiation, and metabolic signaling pathways in plants and animals. Here, we investigate the involvement of SKs in legume nodulation, a process requiring the integration of multiple signaling pathways. We describe a group of SKs in the model legume Lotus japonicus (LSKs), two of which respond to inoculation with the symbiotic nitrogen‐fixing bacterium Mesorhizobium loti. RNAi knock‐down plants and an insertion mutant for one of these genes, LSK1, display increased nodulation. Ηairy‐root lines overexpressing LSK1 form only marginally fewer mature nodules compared with controls. The expression levels of genes involved in the autoregulation of nodulation (AON) mechanism are affected in LSK1 knock‐down plants at low nitrate levels, both at early and late stages of nodulation. At higher levels of nitrate, these same plants show the opposite expression pattern of AON‐related genes and lose the hypernodulation phenotype. Our findings reveal an additional role for the versatile SK gene family in integrating the signaling pathways governing legume nodulation, and pave the way for further study of their functions in legumes. 相似文献
326.
Schubert C Schalk-Hihi C Struble GT Ma HC Petrounia IP Brandt B Deckman IC Patch RJ Player MR Spurlino JC Springer BA 《The Journal of biological chemistry》2007,282(6):4094-4101
The cFMS proto-oncogene encodes for the colony-stimulating factor-1 receptor, a receptor-tyrosine kinase responsible for the differentiation and maturation of certain macrophages. Upon binding its ligand colony-stimulating factor-1 cFMS autophosphorylates, dimerizes, and induces phosphorylation of downstream targets. We report the novel crystal structure of unphosphorylated cFMS in complex with two members of different classes of drug-like protein kinase inhibitors. cFMS exhibits a typical bi-lobal kinase fold, and its activation loop and DFG motif are found to be in the canonical inactive conformation. Both ATP competitive inhibitors are bound in the active site and demonstrate a binding mode similar to that of STI-571 bound to cABL. The DFG motif is prevented from switching into the catalytically competent conformation through interactions with the inhibitors. Activation of cFMS is also inhibited by the juxtamembrane domain, which interacts with residues of the active site and prevents formation of the activated kinase. Together the structures of cFMS provide further insight into the autoinhibition of receptor-tyrosine kinases via their respective juxtamembrane domains; additionally the binding mode of two novel classes of kinase inhibitors will guide the design of novel molecules targeting macrophage-related diseases. 相似文献
327.
Florian Kipfmueller Jessica Schneider Julia Prusseit Ioanna Dimitriou Berndt Zur Axel R. Franz Peter Bartmann Andreas Mueller 《PloS one》2015,10(4)
Introduction
The role of CD64 in late onset sepsis (LOS) in preterm infants has been described in several studies. Aim of this study was to investigate whether CD64 expression is increased in the days before clinical manifestation of LOS.Methods
Patients with birth weight below 1,500g were eligible for study participation. During routine blood sampling CD64 index was determined between day of life 4 and 28. Patients were allocated to one of four groups: (1) blood-culture positive sepsis, (2) clinical sepsis, (3) symptoms of infection without biochemical evidence of infection, or (4) patients without suspected infection. Kinetics of CD64 expression were compared during a period before and after the day of infection in the respective groups.Results
50 infants were prospectively enrolled and allocated to each group as follows: group (1) n = 7; group (2) n = 10; group (3) n = 8; and group (4) n = 25. CD64 index was elevated in 57% of patients in group (1) at least two days before infection. In contrast only 20% in the clinical sepsis group and 0% in group (3) had an elevated CD64 index in the days before infection. 10 of the 25 patients in the control group (4) presented increased CD64 index values during the study period.Conclusions
The CD64 index might be a promising marker to detect LOS before infants demonstrate signs or symptoms of infection. However, larger prospective studies are needed to define optimal cut-off values and to investigate the role of non-infectious inflammation in this patient group. 相似文献328.
Dimitris Vlastos Elena Drosopoulou Ioanna Efthimiou Maximos Gavriilidis Dimitra Panagaki Krystalenia Mpatziou Paraskevi Kalamara Despoina Mademtzoglou Penelope Mavragani-Tsipidou 《PloS one》2015,10(6)
Chios mastic oil (CMO), the essential oil derived from Pistacia lentiscus (L.) var. chia (Duham), has generated considerable interest because of its antimicrobial, anticancer, antioxidant and other beneficial properties. In the present study, the potential genotoxic activity of CMO as well as its antigenotoxic properties against the mutagenic agent mitomycin-C (MMC) were evaluated by employing the in vitro Cytokinesis Block MicroNucleus (CBMN) assay and the in vivo Somatic Mutation And Recombination Test (SMART). In the in vitro experiments, lymphocytes were treated with 0.01, 0.05 and 0.10% (v/v) of CMO with or without 0.05 μg/ml MMC, while in the in vivo assay Drosophila larvae were fed with 0.05, 0.10, 0.50 and 1.00% (v/v) of CMO with or without 2.50 μg/ml MMC. CMO did not significantly increase the frequency of micronuclei (MN) or total wing spots, indicating lack of mutagenic or recombinogenic activity. However, the in vitro analysis suggested cytotoxic activity of CMO. The simultaneous administration of MMC with CMO did not alter considerably the frequencies of MMC-induced MN and wing spots showing that CMO doesn’t exert antigenotoxic or antirecombinogenic action. Therefore, CMO could be considered as a safe product in terms of genotoxic potential. Even though it could not afford any protection against DNA damage, at least under our experimental conditions, its cytotoxic potential could be of interest. 相似文献
329.
330.
Markos Ioannou Panayiotis J Papagelopoulos Ioannis Papanastassiou Ioanna Iakovidou Stamatios Kottakis Nikolaos Demertzis 《World journal of surgical oncology》2008,6(1):1-5