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4812. Cardiac stem cell aging and heart failureDaniela Cesselli, Aneta Aleksova, Elisa Mazzega, Angela Caragnano, Antonio Paolo Beltrami, 2017, pregledni znanstveni članek Opis: A side effect of the medical improvements of the last centuries is the progressive aging of the world population, which is estimated to reach the impressive number of 2 billion people with more than 65 years by 2050. As a consequence, age-related diseases, such as heart failure, will affect more and more patients in the next years. To understand the biological bases of these diseases will be a crucial task in order to find better treatments, and possibly slow age-related morbidity and mortality.
Cardiac stem cells have been at the center of a heated debate and their potential involvement in cardiac homeostasis has been questioned. In this review, we summarize evidence obtained by independent groups, on different animal models and humans, that strongly support the important role played by immature, cardiac resident cells in the cardioprotection against heart failure. Ključne besede: Aging, Heart failure, Cardiomyocyte turnover, Stem cells, Cell senescence, cKit, Sca1, PDGFRα, Cardiospheres Objavljeno v RUNG: 28.03.2017; Ogledov: 4557; Prenosov: 0 Gradivo ima več datotek! Več... |
4813. RiitaO ittinenB, lancaA naR oigR echou(c oords(.2) 016): A GrcyB ackgroundin Childrcn'sli terqtute:D edth,S hipwrcck,W qr, and Disasters Literatura infantil y juvenil con fondo gris: muerte, naufrcgiosg,u errasy desastres. Miinchenl:u d i ci um Ver lag;3 27p p,Barbara Pregelj, 2016, recenzija, prikaz knjige, kritika Opis: Recenzija znanstvene monografije z navedenim naslovom, ki je izšla v angleščini in španščini. Ključne besede: španska mladinska književnost, problemska književnost, vojna, revščina, morje, recepcija Objavljeno v RUNG: 28.03.2017; Ogledov: 4076; Prenosov: 0 Gradivo ima več datotek! Več... |
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4815. A targeted search for point sources of EeV photons with the Pierre Auger ObservatoryA. Aab, Andrej Filipčič, Gašper Kukec Mezek, Ahmed Saleh, Samo Stanič, Marta Trini, Serguei Vorobiov, Lili Yang, Danilo Zavrtanik, Marko Zavrtanik, 2017, izvirni znanstveni članek Ključne besede: astrofizika osnovnih delcev, kozmični žarki, analiza podatkov, izvori visokoenrgijskih fotonov, observatorij Pierre Auger Objavljeno v RUNG: 22.03.2017; Ogledov: 4434; Prenosov: 0 Gradivo ima več datotek! Več... |
4816. Analysis of mechanosensing in human cardiac stem cellsElisa Mazzega, Eliana Pomarè, Angela Caragnano, Sebastian Martewicz, Nicola Elvassore, Antonio Paolo Beltrami, Ugo Livi, 2015, objavljeni povzetek znanstvenega prispevka na konferenci Opis: Objectives: We have shown that age and pathology impair the biological properties of stem cells isolated from human hearts (CSC) and functional assays showed differences between CSC isolated from normal (DCSC) and end-stage failing (ECSC) hearts. As alterations of mechanical properties of the myocardium, such as stiffening and increased wall stress, are crucial features of cardiac remodeling, this work addresses the biological effects exerted on CSC by mechanical stimuli. Materials and methods: DCSC and ECSC were cultured under defined conditions to mimic specific features of the pathologic condition: increased mechanical loading (up to 15%, cyclic at 1 Hz), differential substrate stiffness (ranging from 1 to 231 kPa), differential cell densities. After 24, 48 and 72 h, cells were fixed and stained for analysis of proliferation and subcellular localization of YAP or lysed for RT-PCR analysis.Results: Cyclic stretch was significantly associated with both increased proliferation of DCSC (n = 6, p<0.0001) and ECSC (n = 4, p = 0.003), and with a significant reduction of nuclear localized YAP (nYAP) as a function of time (p<0.05). However, while significant correlation between cell density and decreased nYAP (p = 0.003, r2 = 0.37) characterized ECSC, this was not evident for unstretched DCSC, suggesting a less stringent regulation of contact inhibition in DCSC. These data were further confirmed by seeding cells at differential density. As opposed to what previously shown for epithelial cell lines, DCSC did not reduce nYAP positivity as a function of cell density, when grown in serum containing medium, suggesting that soluble factors present in the serum could maintain the nuclear localization of YAP, independently from the cell density. In line, serum significantly increased the nYAP expressing cells in DCSC, while a significant positive correlation between cell density and nYAP positivity can be demonstrated in DCSC cultured in serum free medium. RT-PCR for YAP-regulated targets confirmed immuno- fluorescence data. Furthermore, independently from the pathologic status, cyclic stretch was significantly associated with a persistent YAP signaling at high cell density. Besides, tension and assembly of cytoskeletal network, induced by increasing substrate stiffness, correlates with nYAP (p<0.05) and YAP transcriptional activation (p<0.05). Conclusions: D- and ECSC differ in their mechanosensing properties. However, in the first cell type, nYAP localization is dictated by the combined action of paracrine factors and cytoskeletal tension, thus reducing the contact inhibition effect. This finding is in line with a more primitive phenotype of SC isolated from normal hearts. Ključne besede: Stem cells, human cardiac stem cells, mechanosensing, mechanotransduction, heart failure, YAP Objavljeno v RUNG: 21.03.2017; Ogledov: 4402; Prenosov: 0 Gradivo ima več datotek! Več... |
4817. Development and Validation of a High- Performance Liquid Chromatography– Tandem Mass Spectrometry Method for the Simultaneous Determination of Irinotecan and Its Main Metabolites in Human Plasma and Its Application in a Clinical Pharmacokinetic StudyBianca Posocco, Elisa Mazzega, Elena Marangon, Giuseppe Toffoli, 2015, izvirni znanstveni članek Opis: Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC). This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients’ genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28) has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite) to SN-38 glucuronide (SN-38G) leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients’ plasma, we developed and validated a new, sensitive and specific HPLC–MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm) using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R20.9962) over the concentration ranges (10–10000 ng/mL for irinotecan, 1–500 ng/mL for SN-38 and SN-38G and 1–5000 ng/mL for APC) and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method wassuccessfully applied to a pharmacokinetic study in metastatic CRC patients enrolled in a genotype-guided phase Ib study of irinotecan administered in combination with 5-fluorouracil/ leucovorin and bevacizumab. Ključne besede: Pharmacokinetic, pharmacodynamics, phase I clinical study, colorectal cancer, Mass spectrometry, pharmacogenetics Objavljeno v RUNG: 21.03.2017; Ogledov: 4625; Prenosov: 0 Gradivo ima več datotek! Več... |
4818. 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, izvirni znanstveni članek Opis: 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. Ključne besede: Stem cells, Myocardial infarction, Cellular senescence, Heart failure Objavljeno v RUNG: 21.03.2017; Ogledov: 4073; Prenosov: 0 Gradivo ima več datotek! Več... |
4819. Growth mechanism and structure of electrochemically synthesized dendritic polymethylsilane moleculesAndraž Mavrič, Artem Badasyan, Gregor Mali, Matjaž Valant, 2017, izvirni znanstveni članek Opis: The study of an electrochemical synthesis of polymethylsilane from trifunctional trichloro-
methylsilane monomers identified a single polymerization pathway involving reduction of the
monomer to silyl anions and their addition to the growing polymer. The sizes of the synthesized
macromolecules, measured with dynamic light scattering, are much larger than the theoretical
size estimated for an ideal dendrimer. The reason for this, found by NMR analysis, is in a large
number of branching irregularities (defects) contained in the molecular structure, which can be
described as a hyperbranched dendritic polymer. Theoretical estimates of sizes for an ideal
dendrimer were corrected assuming a branching defect is a cavity with the volume of one
monomer. Appropriateness of the theoretical and experimental models was confirmed with a
good quantitative agreement between the experimental densities and the theoretically calculated
values. Ključne besede: Polymethylsilane
Dendritic polymer
Electropolymerization Objavljeno v RUNG: 20.03.2017; Ogledov: 4392; Prenosov: 14 Celotno besedilo (705,04 KB) |
4820. Hair cortisol and testosterone concentrations and semen production of Bos taurus bullsGiuseppe Stradaioli, Tanja Peric, Marta Montillo, Antonella Comin, Mirco Corazzin, Maria Cristina Veronesi, Alberto Prandi, 2017, izvirni znanstveni članek Opis: The experiment was aimed to evaluate the usefulness of hair cortisol concentrations (HCC) in revealing the activation of the hypothalamic-pituitary-adrenal (HPA) axis due to the passage of
young bulls from genetic rearing stations to artificial insemination (AI) centre and the influence of this passage on hair testosterone concentrations (HTC). Hair samples on 33 yearling bulls were collected at the time of arrival (ST1) to the AI centre and 3 more hair samples (ST2, ST3, ST4) were collected at monthly intervals. After the end of quarantine each animal was submitted to the standard procedures for collection and production of semen. Overall HCC were significantly affected by period of collection (p<.01). In particular, HCC was higher in samples obtained after finishing the quarantine period (ST2) compared with those obtained on ST1. After ST2, the HCC decreased reaching at ST4 a value similar to that recorded at ST1. An effect of sampling time on HTC was not found (p>.05). The effect of breed was observed only for HTC that was higher in PRI than BS (p<.01). The HCC group have not influenced the semen variables
(p>.05). On the contrary, the effect of breed was evident. The results of this study replicated the effects of a major environmental stressor on mean cortisol concentrations assessed in hair, and add to the growing body of evidence that HCC is an effective and simply collected marker for long-term activity of the HPA system in response to persistent environmental challenge. Ključne besede: Hair, bulls, cortisol, testosterone, semen Objavljeno v RUNG: 20.03.2017; Ogledov: 5621; Prenosov: 0 Gradivo ima več datotek! Več... |