University of Teramo

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    Preliminary multi-omics analysis of BDNF effects in an ischemic stroke model of cerebral organoids

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    Annual Meeting of the PhD Course in Cellular and Molecular BiotechnologiesStroke is a complex and heterogeneous neurological condition characterized by high mortality. It represents the primary cause of long-term disability and cognitive decline, and it ranks as the third leading cause of death in Western countries [1]. Brain-derived neurotrophic factor (BDNF) is a neurotrophin recognized for its essential role in promoting neuroprotection and supporting neuroplasticity [2]. Brain organoids serve as a valuable platform for studying ischemic stroke, as they are three-dimensional cellular models that recapitulate the cellular architecture and composition of the human brain. In this preliminary study, a multi-omics approach was used to assess the effects of BDNF treatment in a cerebral organoid-based stroke model. This strategy enables a comprehensive evaluation of the molecular mechanisms and pathways involved in ischemic injury and the response to BDNF treatment [3]. Cerebral organoids were generated from human induced pluripotent stem cells (hiPSCs) and characterized at different stages using specific maturation markers. To model ischemic stroke, various durations of oxygen and glucose deprivation (OGD) were tested, and a sublethal condition was selected to test the neurotrophin. We performed a detailed characterization of the stroke model of organoids based on Western blotting (WB), dPCR, immunofluorescence, and electrophysiological evaluation providing a comprehensive overview of the cellular responses. Subsequently, we focused on proteomic analysis using WB and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE). These techniques enable the investigation of pathway modulation induced by BDNF treatment. Additionally, transcriptomic profiling was performed using the Ion Torrent platform. Together, these data are crucial for elucidating the molecular mechanisms and therapeutic potential of BDNF. In conclusion, this preliminary multi-omics study on cerebral organoids offers novel insights into the effects of BDNF in a 3D stroke model, supporting its application in ischemic stroke brain injury. Keywords: Brain organoids; Multi-omics; Ischemic Stroke. 1. Feigin VL, Krishnamurthi RV, Parmar P, et al. Update on the Global Burden of Ischemic and Hemorrhagic Stroke in 1990-2013: The GBD 2013 Study. Neuroepidemiology. 2015;45(3):161-176. 2. Chen A, Xiong L, Tong Y and Mao M: The neuroprotective roles of BDNF in hypoxic ischemic brain injury (Review). Biomed Rep 1: 167-176, 2013. 3. Li W, Shao C, Zhou H, et al. Multi-omics research strategies in ischemic stroke: A multidimensional perspective. Ageing Res Rev. 2022;81:101730. Acknowledgements: This research was funded by Dompé farmaceutici S.p.A, by Progetto n. 74 – Piattaforma tecnologica integrata per l’identificazione e lo sviluppo di neurotrofine per il trattamento di patologie neurosensoriali a carico degli organi di vista e udito e patologie del CNS, rare o ad elevato bisogno di cura insoddisfatto (PINNACOLO) - CUP B19J23000180005 and by European Union-NextGenerationEU under the Italian University and Research (MUR) National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006. ERC: LS2, LS3, LS

    Guerra e pace nelle società del rischio

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    Sulle tracce del principio di giustizia. Diritto alla salute e consenso informato all'atto medico nel diritto europeo

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    Il diritto alla salute e il consenso informato sono correlati al principio di giustizia. Un principio che richiede il rispetto della persona, della dignità umana e dei diritti fondamentali di ogni uomo. Esso costituisce l’asse portantedell’Unione, uno dei principi fondamentali che ha guidato la costruzione del diritto europeo e che mira a garantire che le leggi e le politiche europee siano eque eimparziali. Le sue tracce emergono sia nei Trattati, sia nella Carta dei diritti fondamentali dell’UE.Il lavoro si propone di analizzare l’incidenza del principio di giustizia sul diritto alla salute e sul diritto al consenso informato nel diritto europeo, anche con riferimento alla dimensione metafisica e trascendentale della persona, al fine di evidenziare inadeguatezze, carenze e strategie di intervento.ABSTRACT: The right to health and the right to informed consent are related to the principle of justice. It is a principle that requires respect for the person, human dignity and the fundamental rights of every human being. It constitutes the backboneof the European Union, one of the fundamental principles that has led the construction of European law and aims to ensure that European laws and policies are fair and impartial. Its traces emerge in both the European Treaties and the EU Charter of Fundamental Rights. The paper aims to analyze the impact of the principle of justice on the right to health and the right to informed consent in European law, including with reference to the metaphysical and transcendental dimensions of the person, in order to highlightinadequacies, shortcomings, and strategies for interventio

    La donazione di cosa altrui

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    Type-1 Cannabinoid Receptor Promiscuous Coupling: Computational Insights into Receptor-G Protein Interaction Dynamics

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    Cannabinoid receptor (CB1), a G protein coupled receptor (GPCR), is a known pharmacological target in several diseases and modulates key physiological processes through Gi protein-mediated signaling. However, recent evidence suggests that CB1 can also activate other G proteins, including the stimulatory Gs protein, a phenomenon with unclear structural determinants. Here, we use a computational approach to elucidate the structural basis of the CB1-Gs interaction. Protein–protein docking and extensive molecular dynamics simulations yield a model for the CB1-Gs complex that agrees well with both existing experimental data and available GPCR-Gs structures, supporting its validity. This work provides new insights into the structural basis of CB1’s ability to couple with different G-proteins. The model provides a basis for future studies dissecting the functional consequences of CB1-Gs signaling and the development of improved therapeutics targeting the CB1 receptor and the wider endocannabinoid system

    Wood-resident yeasts: A tool for healthier and more sustainable winemaking

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    The use of non-Saccharomyces yeasts in wine production has gained attention not only for their impact on wine quality and complexity but also for their potential health benefits. Therefore, it is essential to explore unusual ecological niches to isolate yeast species with peculiar metabolic and physiological properties. In this study, the yeasts inhabiting the interior surface of the wine barrels were studied. In particular, the yeasts were tested for some healthy properties including the production of γ-aminobutyric acid (GABA) and antioxidant activity. The species detected were Zygosaccharomyces bisporus, Zygosaccharomyces bailii, Millerozyma farinosa, Starmerella lactis-condensi, Wickeramiella versatilis, and Zygosaccharomyces rouxii. The highest GABA production was detected for S. lactis-condensi, Z. bisporus and Z. rouxii. A certain intra-species and inter-species variability was detected for the anti-oxidant activity. The Z. bailii, S. lactis-condensi, and Z. rouxii strains showed the highest DPPH and ABTS radical-scavenging activity. The lowest activity was shown by the W. versatilis strains. The use of the yeasts selected in this study with health-promoting properties in winemaking aligns with sustainability goals by enhancing both the nutritional value of wine and the efficiency of the production process. In particular, the high-GABA-producing strains detected as well as the strains with excellent anti-oxidant activity could be proposed as healthful microorganisms for the production of functional beverages or natural antioxidant supplements in the wine industry. Moreover, the strains with anti-oxidant activity might enhance the protection of wines from oxidation, thus potentially assuming an important role in the sensorial quality. By integrating these beneficial yeasts into winemaking, the industry can produce wines that are both healthier for consumers and more environmentally responsible

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