20 research outputs found

    Cardiac fibroblasts and mechanosensation in heart development, health and disease

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    The term 'mechanosensation' describes the capacity of cells to translate mechanical stimuli into the coordinated regulation of intracellular signals, cellular function, gene expression and epigenetic programming. This capacity is related not only to the sensitivity of the cells to tissue motion, but also to the decryption of tissue geometric arrangement and mechanical properties. The cardiac stroma, composed of fibroblasts, has been historically considered a mechanically passive component of the heart. However, the latest research suggests that the mechanical functions of these cells are an active and necessary component of the developmental biology programme of the heart that is involved in myocardial growth and homeostasis, and a crucial determinant of cardiac repair and disease. In this Review, we discuss the general concept of cell mechanosensation and force generation as potent regulators in heart development and pathology, and describe the integration of mechanical and biohumoral pathways predisposing the heart to fibrosis and failure. Next, we address the use of 3D culture systems to integrate tissue mechanics to mimic cardiac remodelling. Finally, we highlight the potential of mechanotherapeutic strategies, including pharmacological treatment and device-mediated left ventricular unloading, to reverse remodelling in the failing heart

    Cerium Oxide Nanoparticles Protect Cardiac Progenitor Cells from Oxidative Stress

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    Cardiac progenitor cells (CPCs) are a promising autologous source of cells for cardiac regenerative medicine. However, CPC culture in vitro requires the presence of microenvironmental conditions (a complex array of bioactive substance concentration, mechanostructural factors, and physicochemical factors) closely mimicking the natural cell surrounding in vivo, including the capability to uphold reactive oxygen species (ROS) within physiological levels in vitro. Cerium oxide nanoparticles (nanoceria) are redox-active and could represent a potent tool to control the oxidative stress in isolated CPCs. Here, we report that 24 h exposure to 5, 10, and 50 !g/mL of nanoceria did not a!ect cell growth and function in cardiac progenitor cells, while being able to protect CPCs from H2O2-induced cytotoxicity for at least 7 days, indicating that nanoceria in an e!ective antioxidant. Therefore, these "ndings con"rm the great potential of nanoceria for controlling ROS-induced cell damage

    Notulae to the Italian native vascular flora: 6

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    In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations and status changes to the Italian administrative regions for taxa in the genera Alchemilla, Arundo, Bupleurum, Clematis, Clinopodium, Cota, Crassula, Cytisus, Euphorbia, Hieracium, Isoëtes, Lamium, Leontodon, Linaria, Lychnis, Middendorfia, Ophrys, Philadelphus, Pinus, Sagina, Sedum, Taeniatherum, Tofieldia, Triticum, Veronica, and Vicia. Nomenclature and distribution updates, published elsewhere, and corrigenda are provided as supplementary material

    Notulae to the Italian native vascular flora: 6

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    In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations and status changes to the Italian administrative regions for taxa in the genera Alchemilla, Arundo, Bupleurum, Clematis, Clinopodium, Cota, Crassula, Cytisus, Euphorbia, Hieracium, Isoëtes, Lamium, Leontodon, Linaria, Lychnis, Middendorfia, Ophrys, Philadelphus, Pinus, Sagina, Sedum, Taeniatherum, Tofieldia, Triticum, Veronica, and Vicia. Nomenclature and distribution updates, published elsewhere, and corrigenda are provided as supplementary material

    Mesenchymal stem cell adhesion but not plasticity is affected by high substrate stiffness

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    The acknowledged ability of synthetic materials to induce cell-specific responses regardless of biological supplies provides tissue engineers with the opportunity to find the appropriate materials and conditions to prepare tissue-targeted scaffolds. Stem and mature cells have been shown to acquire distinct morphologies in vitro and to modify their phenotype when grown on synthetic materials with tunable mechanical properties. The stiffness of the substrate used for cell culture is likely to provide cells with mechanical cues mimicking given physiological or pathological conditions, thus affecting the biological properties of cells. The sensitivity of cells to substrate composition and mechanical properties resides in multiprotein complexes called focal adhesions, whose dynamic modification leads to cytoskeleton remodeling and changes in gene expression. In this study, the remodeling of focal adhesions in human mesenchymal stem cells in response to substrate stiffness was followed in the first phases of cell–matrix interaction, using poly-Δ-caprolactone planar films with similar chemical composition and different elasticity. As compared to mature dermal fibroblasts, mesenchymal stem cells showed a specific response to substrate stiffness, in terms of adhesion, as a result of differential focal adhesion assembly, while their multipotency as a bulk was not significantly affected by matrix compliance. Given the sensitivity of stem cells to matrix mechanics, the mechanobiology of such cells requires further investigations before preparing tissue-specific scaffolds

    Perfluoro-tagged phosphine-free palladium nanoparticles supported on silica gel: application to alkynylation of aryl halides, Suzuki–Miyaura cross-coupling, and Heck reactions under aerobic conditions

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    The utilization of perfluoro-tagged palladium nanoparticles immobilized on fluorous silica gel through fluorous–fluorous interactions (Pdnp–A/FSG) or through covalent bonding to silica gel (Pdnp–B) in the alkynylation of aryl halides, in the Suzuki–Miyaura cross-coupling, as well as in the Heck reaction between methyl acrylate and aryl iodides is described. The reactions are carried out under aerobic and phosphine-free conditions with excellent to quantitative product yields in each case. The catalysts are easily recovered and reused several times without significant loss of activity. The alkynylation of aryl halides (under copper-free conditions) and the Suzuki–Miyaura cross-coupling are carried out in water. The Heck reaction of methyl acrylate with aryl iodides is best performed in MeCN. The utilization of Pdnp–B in the synthesis of 2,3-disubstituted indoles from 2-(alkynyl)trifluoroacetanilides and aryl halides is also reported

    Biomaterial and implant induced ossification:in vitro and in vivo findings

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    Abstract Material‐induced ossification is suggested as a suitable approach to heal large bone defects. Fiber‐reinforced composite–bioactive glasses (FRC‐BGs) display properties that could enhance the ossification of calvarial defects. Here, we analyzed the healing processes of a FRC‐BG implant in vivo from the perspective of material‐induced ossification. Histological analysis of the implant, which was removed 5 months after insertion, showed the formation of viable, noninflammatory mesenchymal tissue with newly‐formed mineralized woven bone, as well as nonmineralized connective tissue with capillaries and larger blood vessels. The presence of osteocytes was detected within the newly generated bone matrix. To expand our understanding on the osteogenic properties of FRC‐BG, we cultured human adipose tissue‐derived mesenchymal stromal cells (AD‐MSCs) in the presence of two different BGs (45S5 and S53P4) and Al2O3 control. AD‐MSCs grew and proliferated on all the scaffolds tested, as well as secreted abundant extracellular matrix, when osteogenic differentiation was appropriately stimulated. 45S5 and S53P4 induced enhanced expression of COL2A1, COL10A1, COL5A1 collagen subunits, and pro‐osteogenic genes BMP2 and BMP4. The concomitant downregulation of BMP3 was also detected. Our findings show that FRC‐BG can support the vascularization of the implant and the formation of abundant connective tissue in vivo. Specifically, BG 45S5 and BG S53P4 are suited to evoke the osteogenic potential of host mesenchymal stromal cells. In conclusion, FRC‐BG implant demonstrated material‐induced ossification both in vitro and in vivo
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