How Diet Intervention via Modulation of DNA Damage Response through MicroRNAs May Have an Effect on Cancer Prevention and Aging, an in Silico Study

The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in silico analysis by the DIANA-mirPathv3 software. The in silico analysis allowed us to identify pathways shared by different miRs involved in DD/DDR vis-à-vis the specific compounds. The results demonstrate that certain miRs (e.g., -146, -21) play a central role in the interplay among DD/DDR and the bioactive compounds. Furthermore, some specific pathways, such as fatty acids biosynthesis/metabolism , extracellular matrix-receptor interaction and signaling regulating the pluripotency of stem cells , appear to be targeted by most miRs affected by the studied compounds. Since DD/DDR and these pathways are strongly related to aging and carcinogenesis, the present in silico results of our study suggest that monitoring the induction of specific miRs may provide the means to assess the antiaging and chemopreventive properties of particular dietary compounds

Together Beyond Accession: Turkey as the EU’s Indispensable Partner. College of Europe Policy Brief #15.18, November 2018

> Following turbulent years in European Union-Turkey relations, the June 2018 elections in Turkey and the prospective appointment of a new European Commission following the 2019 European Parliament elections provide a window of opportunity to take stock of the deadlock in Turkey’s EU bid. > Incoming European leaders should engage in a profound rethinking of EU-Turkey relations, beyond the accession perspective. > Concretely, the incoming Commission and especially High Representative should push for a renewal of EU strategic engagement with Turkey to ensure ‘togetherness’ in addressing changing geopolitical, economic and security equilibria. This engagement should rely on a four-pillar, multidimensional approach: > Amid growing economic instability in Turkey, we suggest advancing towards an updated Customs Union, while seizing on Turkey’s potential as a central hub in the Southern Energy Corridor. > This strong economic asset could leverage further EU engagement on human rights, rule of law and democracy and enable the Union to adopt innovative measures in support of Turkish civil society. > International developments have positioned Turkey as a crucial, albeit ambivalent, foreign policy partner, especially in the Middle East. For this reason, the EU should promote active foreign policy coordination and cooperation with Turkey. > Migration has been a rare, yet sensitive area of cooperation. In this domain, emphasis should be placed on enhancing the implementation of the 2016 EU-Turkey Statement

Native extracellular matrix: a new scaffolding platform for repair of damaged muscle

Effective clinical treatments for volumetric muscle loss resulting from traumatic injury or resection of a large amount of muscle mass are not available to date. Tissue engineering may represent an alternative treatment approach. Decellularization of tissues and whole organs is a recently introduced platform technology for creating scaffolding materials for tissue engineering and regenerative medicine. The muscle stem cell niche is composed of a three-dimensional architecture of fibrous proteins, proteoglycans, and glycosaminoglycans, synthesized by the resident cells that form an intricate extracellular matrix (ECM) network in equilibrium with the surrounding cells and growth factors. A consistent body of evidence indicates that ECM proteins regulate stem cell differentiation and renewal and are highly relevant to tissue engineering applications. The ECM also provides a supportive medium for blood or lymphatic vessels and for nerves. Thus, the ECM is the nature's ideal biological scaffold material. ECM-based bioscaffolds can be recellularized to create potentially functional constructs as a regenerative medicine strategy for organ replacement or tissue repopulation. This article reviews current strategies for the repair of damaged muscle using bioscaffolds obtained from animal ECM by decellularization of small intestinal submucosa (SIS), urinary bladder mucosa (UB), and skeletal muscle, and proposes some innovative approaches for the application of such strategies in the clinical setting

Extracellular pH, osmolarity, temperature and humidity could discourage SARS-CoV-2 cell docking and propagation via intercellular signaling pathways

open9sì: The COVID-19 pandemic and its virus variants continue to pose a serious and long-lasting threat worldwide. To combat the pandemic, the world's largest COVID-19 vaccination campaign is currently ongoing. As of July 19th 2021, 26.2% of the world population has received at least one dose of a COVID-19 vaccine (1.04 billion), and one billion has been fully vaccinated, with very high vaccination rates in countries like Israel, Malta, and the UEA. Conversely, only 1% of people in low-income countries have received at least one dose with examples of vaccination frequency as low as 0.07% in the Democratic Republic of Congo. It is thus of paramount importance that more research on alternate methods to counter cell infection and propagation is undertaken that could be implemented in low-income countries. Moreover, an adjunctive therapeutic intervention would help to avoid disease exacerbation in high-rate vaccinated countries too. Based on experimental biochemical evidence on viral cell fusion and propagation, herein we identify (i) extracellular pH (epH), (ii) temperature, and (iii) humidity and osmolarity as critical factors. These factors are here in discussed along with their implications on mucus thick layer, proteases, abundance of sialic acid, vascular permeability and exudate/edema. Heated, humidified air containing sodium bicarbonate has long been used in the treatment of certain diseases, and here we argue that warm inhalation of sodium bicarbonate might successfully target these endpoints. Although we highlight the molecular/cellular basis and the signalling pathways to support this intervention, we underscore the need for clinical investigations to encourage further research and clinical trials. In addition, we think that such an approach is also important in light of the high mutation rate of this virus originating from a rapid increase.openCicconetti, Franco; Sestili, Piero; Madiai, Valeria; Albertini, Maria Cristina; Campanella, Luigi; Coppari, Sofia; Fraternale, Daniele; Saunders, Bryan; Teodori, LauraCicconetti, Franco; Sestili, Piero; Madiai, Valeria; Albertini, Maria Cristina; Campanella, Luigi; Coppari, Sofia; Fraternale, Daniele; Saunders, Bryan; Teodori, Laur

Restoration versus reconstruction: how cell anatomy and extra-cellular matrix influence tissue regeneration

Tissue regeneration replaces damaged cells and is involved in tissue remodeling. In order to investigate the existence of a leitmotif of tissue regeneration, we compared the cellular aspects of regeneration of epidermis, neurons and skeletal muscle, characterized by different types of histological and functional organization. Following damage, all the tissues here analyzed go through three phases: inflammation, regeneration and maturation. Another common feature is the occurrence of cellular de-differentiation and/or differentiation events, including gene transcription, which are typical of embryonic development. Nonetheless, various strategies are used by different tissues to replace their lost parts. The epidermis regenerates ex novo, whereas neurons restore their missing parts; muscle fibers use a mixed strategy, based on the regrowth of missing parts through reconstruction by means of newborn fibers. The choice of either strategy is influenced by the physical, chemical and structural features of the cells as well as by the extracellular matrix typical of a given tissue, which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration. Taking skeletal muscle as a model, we present evidence about the importance of the fiber niche to direct and favour tissue regeneration, a phenomenon of particular relevance for highly hierarchized tissues such as striated muscles. Niche properties are accounted for by cell-cell contacts, cell-matrix interaction and paracrine effects in skeletal muscle. The ordered sequence of steps that characterizes the regeneration processes, shared by several tissues, suggests it may be possible to model this extremely important phenomenon to improve guided in situ regeneration interventions

L'analisi economico-finanziaria dei macro settori di attività

Analisi economico-finanziaria complessiva delle imprese della Lombardia, articolate per macro settori di attività e aree geografiche, su un periodo temporale di sei ann