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Abstract: A quick, easy and green water-based synthesis protocol involving coprecipitation of oxalates combined with hydrothermal treatment resulted in the crystallisation of nanostructured manganites at a relatively low temperature (180 °C). The subcritical hydrothermal approach was shown to play a key role in stabilising phases which are generally achieved at much higher temperatures and under harsher conditions, thus disclosing an exciting alternative for their synthesis. Through this mild wet chemistry approach, the compounds CuMnO2, ZnMn2O4 and ZnMnO3 were synthesised as nanocrystalline powders. Noticeably, the optimised route proved to be effective in stabilising the exotic polymorph cubic spinel ZnMnO3 in pure form. This is particularly notable, as very few records concerning this compound are available in the literature. The compounds were fully characterised from compositional, structural, morphological and magnetic points of view.
Keywords: nanostructured manganites, low temperature wet chemistry synthesis
Published in RUNG: 28.03.2017; Views: 4324; Downloads: 0
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Abstract: 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.
Keywords: Aging, Heart failure, Cardiomyocyte turnover, Stem cells, Cell senescence, cKit, Sca1, PDGFRα, Cardiospheres
Published in RUNG: 28.03.2017; Views: 4512; Downloads: 0
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Keywords: Zofka Kveder, Angela Vode, Berta Bojetu, Suzana Tratnik, Nataša Sukič
Published in RUNG: 28.03.2017; Views: 3958; Downloads: 0
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Abstract: 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.
Keywords: Stem cells, human cardiac stem cells, mechanosensing, mechanotransduction, heart failure, YAP
Published in RUNG: 21.03.2017; Views: 4331; Downloads: 0
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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: 4026; Downloads: 0
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