11. Ex Vivo Molecular Rejuvenation Improves the Therapeutic Activity of Senescent Human Cardiac Stem Cells in a Mouse Model of Myocardial InfarctionElisa Avolio, Giuseppe Gianfranceschi, Angela Caragnano, Emmanouil Athanasakis, Rajesh Katare, Daniela Cesselli, Marco Meloni, Anita Palma, Arianna Barchiesi, Carlo Vascotto, Barbara Toffoletto, Elisa Mazzega, Nicoletta Finato, Giuseppe Aresu, Ugolino Livi, Costanza Emanueli, Giacinto Scoles, Carlo Alberto Beltrami, Paolo Madeddu, Antonio Paolo Beltrami, 2014, original scientific article Abstract: Cardiac stem cells (CSC) from explanted decompensated hearts (E-CSC) are, with respect to those obtained from healthy donors (D-CSC), senescent and functionally impaired. We aimed to identify alterations in signaling pathways that are associated with CSC senescence. Additionally, we inves- tigated if pharmacological modulation of altered pathways can reduce CSC senescence in vitro and enhance their reparative ability in vivo. Measurement of secreted factors showed that E-CSC release larger amounts of proinflammatory cytokine IL1b compared with D-CSC. Using blocking antibodies, we verified that IL1b hampers the paracrine protective action of E-CSC on cardiomyo- cyte viability. IL1b acts intracranially inducing IKKb signaling, a mechanism that via nuclear factor-jB upregulates the expression of IL1b itself. Moreover, E-CSC show reduced levels of AMP protein kinase (AMPK) activating phosphorylation. This latter event, together with enhanced IKKb signaling, increases TORC1 activity, thereby impairing the autophagic flux and inhibiting the phos- phorylation of Akt and cAMP response element-binding protein. The combined use of rapamycin and resveratrol enhanced AMPK, thereby restoring downstream signaling and reducing IL1b secretion. These molecular corrections reduced E-CSC senescence, re-establishing their protective activity on cardiomyocytes. Moreover ex vivo treatment with rapamycin and resveratrol improved E-CSC capacity to induce cardiac repair upon injection in the mouse infarcted heart, leading to reduced cardiomyocyte senescence and apoptosis and increased abundance of endog- enous c-Kit1 CSC in the peri-infarct area. Molecular rejuvenation of patient-derived CSC by short pharmacologic conditioning boosts their in vivo reparative abilities. This approach might prove useful for refinement of CSC-based therapies.
Keywords: Stem cells, Myocardial infarction, Cellular senescence, Heart failure
Published in RUNG: 21.03.2017; Views: 4041; Downloads: 0
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13. Development of a simple method for the extraction of pharmaceuticals from fishTopić Jelena, Klančar Anita, Trontelj Jurij, Roškar Robert, 2016, published scientific conference contribution abstract Abstract: Pharmaceuticals are considered as emerging pollutants of particular concern due to their continuous release into the environment and the potential impact on aquatic organisms. The selection of the target compounds for evaluation in fish tissue was based on physico-chemical properties, bioaccumulation potential and the results of the screening of pharmaceuticals in the effluent of WWTP Sevnica in March 2015. We chose tramadol, risperidone, desipramine, carbamazepine, irbesartan, naproxen, valsartan, atorvastatin, triclosan, simvastatin and diclofenac. The method was developed on muscle tissue and is based on the tissue homogenization with stainless steel beads, followed by extraction with acetonitrile, centrifugation and sample clean-up with solid-phase extraction (SPE). The instrumental analysis was performed with LC-MS/MS. The best and the most reproducible recoveries were observed for the samples that were diluted to 25 mL with 50 mM phosphate buffer pH 7. The method was validated and the linearity range was established, which was in the range of 0.1 – 1000 ng/g, depending of the compound. The recoveries for the target pharmaceuticals were in the range of 24.0 – 108.5 %, with good reproducibility as the relative RSD values for all compounds were below 7.5 %. LOQ values for the compounds were in the 0.1 – 50 ng/g range. We applied the method to the fish tissue samples from the river Sava and from the aquaculture establishment. We chose muscle, liver, skin and kidney tissue samples. The results showed presence of tramadol and carbamazepine in some tissue, but the concentrations were below the LOQ.
Keywords: pharmaceuticals, fish, SPE, LC-MS/MS
Published in RUNG: 16.11.2016; Views: 5705; Downloads: 0
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14. Toxicity of imidacloprid to the terrestrial isopod Porcellio scaber (Isopoda, Crustacea)Mateja Blažič, Cornelis A. M. van Gestel, Anita Jemec, Primož Zidar, Vladka Lešer, Polonca Trebše, Damjana Drobne, 2008, original scientific article Keywords: test toksičnosti, biomarkerji, ekologija, tveganja
Published in RUNG: 16.06.2016; Views: 4326; Downloads: 20
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