Archivio Istituzionale della Ricerca - Università degli Studi di Pavia
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    135341 research outputs found

    Do microplastics (MPs) and nanoplastics (NPs) directly contribute to human carcinogenesis?

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    Microplastics (MPs; 0.1–5000 μm) and nanoplastics (NPs; 1–1000 nm) are ubiquitous contaminants that can enter the human body through the mouth, nose, and skin, where they bioaccumulate in many organs and tissues. The role of MPs/NPs in carcinogenesis is still largely unknown, despite mounting evidence linking them to DNA damage, cellular stress, and inflammation. The toxicokinetic and toxicodynamic mechanisms—absorption, distribution, and molecular interactions—by which MPs/NPs may cause or contribute to cancer are the aim of this review, which provides the first thorough, multidisciplinary investigation of this topic. By combining epidemiological, in vitro, and in vivo data, we are able to discover molecular pathways that may link exposure to carcinogenesis, such as transcription factor modulation and autophagy dysregulation. This review highlights the need for targeted research and coordinated regulatory action to limit the long-term health impact of MPs/NPs by redefining them as possible oncogenic agents in addition to environmental pollutants by emphasizing knowledge gaps and novel molecular targets. This review aims to provide a comprehensive, multidisciplinary synthesis of current knowledge on MPs/NPs to shed light on the toxicokinetic and toxicodynamic processes—absorption, distribution, cellular, and molecular interactions—that may underlie their potential carcinogenicity. In order to establish causation, this review further suggests giving priority to longitudinal epidemiology, physiologically relevant dose setting, and human-relevant mechanistic platforms (organoids, organs-on-chips, and multi-omics)

    C'è un futuro per lo sciopero generale?

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    Detention, Grounds for

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    Driving Social Change Through Transformative Marketing for Gender Equity

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    This volume brings interdisciplinary perspectives to explore how transformative marketing can challenge entrenched gender norms and contribute meaningfully to social progress. Chapters examine gender equity across a wide range of domains, including multinational marketing strategies, influencer-driven consumer behaviour, organizational responses to gender-based violence, educational access, alternative finance ecosystems, supply-chain sustainability, and policymaking frameworks. They suggest how marketing intersects with education, finance, technology, governance, and ethics to shape both individual choices and structural outcomes. Drawing on empirical studies, systematic reviews, spatial analysis, and conceptual frameworks, the book underscores the value of context-sensitive, data-driven, and human-centred approaches to gender-equity initiatives. It stresses the importance of moving beyond symbolic inclusion towards measurable, transformative impact—whether through inclusive branding, equitable access to capital, gender-responsive supply chains, or policy-enabled linkages between global and local enterprises. Intended for scholars, practitioners, policymakers, and students alike, this book offers both critical insight and practical guidance for those seeking to align marketing practice with broader commitments to justice, sustainability, and social responsibility. As markets increasingly mould cultural narratives and economic realities, the volume highlights the potential of transformative marketing to serve as an enduring force for gender equity and inclusive social change

    The Basilica of Santa Maria Maggiore in Lomello Thousand Years of History (1025-2025) between signs and meanings

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    The experimentation of new academic approaches and pedagogical programs needs the collaboration of different institutions. Since 2022 at the University of Pavia, a new methodological approach has been explored and developed for the conservation of the religious sites. This paper aims to show this academic approach where the dialogue between the academic community, the ecclesiastical community and the local people allowed the activation of cultural, social initiatives with the great result of an urban and spiritual regeneration of high relevance. In fact, in 2022, the architectural restoration class of the University of Pavia signed an agreement with the Diocese of Vigevano, Parish of Lomello, to contribute to the knowledge and conservation of this important sacred place located in an area of significant importance to produce rice. The Basilica is located in the historical center of this small village in Lomellina, where the local community was involved in many activities. So, since autumn 2023 the architectural restoration course is based in this Basilica and now every activity is finalized to know very well this heritage and at the same time to valorize it with the help of the local community. The Basilica is a Jubilee seat and in 2025 it will celebrate its thousandth anniversary

    Geodynamic pacemaker of Phanerozoic climate: A multivariate analysis of plate boundary processes and global temperature variations

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    Global long-term surface temperature variations throughout the Phanerozoic are related to changes in concentrations of carbon compounds in the atmosphere, but the deeper the time, the more uncertain becomes the information about carbon budgets and fluxes preserved in geological archives. Although some temporal correlations between climate changes and individual geodynamic processes have been recognized, a comprehensive understanding of the relationships between long-term changes in Global Average Temperature and the ensemble of geodynamic climate-forcing mechanisms throughout the Phanerozoic Eon is elusive. Here, building upon literature data, we perform a simple cross-correlation multivariate analyses to investigate relationships between Phanerozoic Global Average Temperature and different geodynamics occurring along plate boundaries. Our analysis suggests that Earth's climate operates as a multi-driver system, with no single dominant mechanism identifiable throughout the Phanerozoic. In addition, cooling and heating geodynamic processes require different timescales to fully exert their effects on global temperature. These outcomes highlight the necessity of integrative approaches that consider multiple processes to explain the paleoclimate evolution of the Earth. Within this broader framework, the cycles of supercontinent assembly and breakup are key in modulating the relative development of cooling and heating plate margins over geologic timescales, effectively serving as the primary pacemaker of Global Average Temperature variations

    INTERFACING HERITAGES, CULTURES, & LANDSCAPES: PAVING CULTURAL SUSTAINABILITY - Vol.2

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    Within the system of complex interconnectedness and interactions among cultures, heritage, and landscapes and their role in making cultural sustainability—all that is rooted in the past together, we seek to search ways, paths, and means that are implied for framing and creating a base for the UN Sustainable Development Goals Target 11.4, focussing on ‘Transforming our World: The 2030 Agenda for Sustainable Development’. Together with community development, nature-based education, and pilgrimages, revealing the spirit of places is part of the cultural process of transforming landscapes—seen and visualised in the fabric of landscape architecture. These attributes can be examined in relation to the trends and perspectives of the emerging literature and regional representations. The inherent and manifested meanings, symbols, metaphors, aesthetics, etc., exemplify the representations. In contrast to the mundane environment, spirituality offers a bridge through transcendence and connection to the inherent power of serene nature, which is also reflected in architectural symbols. These attributes are clearly visible in the holyheritage cities. This paper presents an introductory review and appraisal of the entire journey and the resultant cultural landscapes, following the path of RWYC - Reconnecting With Your Culture, and attempts to lay out a pathway for cultural and sacred sustainability

    Advances in Fetal Repair of Spina Bifida Integrating Prenatal Surgery, Stem Cells, and Biomaterials

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    Spina bifida (SB) is a congenital malformation of the central nervous system (CNS), re- sulting from incomplete closure of the neural tube (NT) during early embryogenesis. Myelomeningocele (MMC), the most severe form of SB, leads to progressive neurological, orthopedic, and urological dysfunctions due to both NT developmental failure and sec- ondary intrauterine injury (“two-hit hypothesis”). Prenatal repair of MMC has progressed considerably since the Management of Myelomeningocele Study (MOMS, 2011) trial, which showed that open fetal surgery can decrease the need for shunting and improve motor function, although it carries significant maternal risks. To address these limitations, mini- mally invasive techniques have been developed, with the goal of achieving similar benefits for the fetus while reducing maternal morbidity. Recent research has shifted toward regen- erative strategies, integrating mesenchymal stem cells (MSCs), bioengineered scaffolds, and cell-derived products to move beyond mere mechanical protection toward true NT repair. Preclinical studies in rodent and ovine models have shown that amniotic- and placenta- derived MSCs exert neuroprotective and immunomodulatory paracrine effects, promoting angiogenesis, modulating inflammation, and supporting tissue regeneration. Minimally invasive, cell-based interventions such as Transamniotic Stem Cell Therapy (TRASCET), in preclinical rodent models, offer the possibility of very early treatment without hys- terotomy, although translation remains limited by the lack of large-animal validation and long-term safety data. In parallel, advances in biomaterials, nanostructured scaffolds, and exosome-based therapies reinforce a regenerative paradigm that may improve neurological outcomes and quality of life in affected children. Ongoing translational studies are essen- tial to optimize these approaches and define their safety and efficacy in clinical settings. This review provides an integrated overview of embryological mechanisms, diagnostic strategies, and prenatal therapeutic advances in SB treatment, with emphasis on prenatal repair, fetal surgery and emerging regenerative approaches

    DESIGN AND DEVELOPMENT OF GLASS VIALS SILICONIZATION TO MINIMIZE THE INTERACTION WITH BIOTECH- AND NANO-DRUG PRODUCTS

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    I flaconi in vetro borosilicato di tipo I sono generalmente considerati chimicamente inerti, ma possono deteriorarsi in presenza di sollecitazioni chimiche, fisiche o meccaniche. In questo lavoro, flaconi di tipo I (non trattati, solfonati o rivestiti con PDMS) sono stati sottoposti a trattamenti termici di lavaggio, depirogenazione e sterilizzazione a calore umido, mediante diverse combinazioni di temperatura e tempo di esposizione mantenendo lo stesso tempo equivalente F0. La degradazione superficiale è stata valutata mediante SEM e AFM, rispettivamente per morfologia, topografia e rugosità; sono state inoltre analizzate le proprietà nanomeccaniche, la resistenza idrolitica (ICP) e la composizione chimica superficiale tramite XPS. Dopo sterilizzazione, i flaconi rivestiti con PDMS hanno mostrato un aumento dei difetti e della rugosità superficiale, mentre i vials trattati con solfato d’ammonio sono rimasti stabili. Nanoparticelle lipidiche solide (SLN) e albumina sierica bovina (BSA) sono state impiegate come sistemi modello per indagare l’adsorbimento superficiale dopo i trattamenti termici; l’adsorbimento delle nanoparticelle è stato valutato mediante NTA e quello della BSA mediante CD. Per entrambi i sistemi, non si è registrato un aumento significativo del processo di adsorbimento o di alterazione della struttura secondaria proteica a seguito di desorbimento. In futuro verranno presi in considerazione sia nuove tecnologie di rivestimento che differenti prodotti nanoparticellari e biotecnologici, per migliorare il controllo delle interazioni farmaco-contenitore.Type I borosilicate vials are generally considered inert, but under certain chemical, physical, or mechanical stresses they can undergo deterioration. In this work, Type I vials (untreated, sulfonated, or PDMS-coated) were subjected to thermal treatments of washing, depyrogenation, and steam sterilization, using different combinations of temperature and exposure time while maintaining an equivalent F0. Surface degradation was assessed by SEM for morphology and by AFM for topography and roughness. Nanomechanical properties, hydrolytic resistance (ICP) and surface chemical composition (XPS) were also evaluated. Following sterilization, PDMS-coated vials exhibited increased defects and surface roughness, whereas sulfonated coatings remained stable. Solid lipid nanoparticles (SLNs) and bovine serum albumin (BSA) were selected as model systems to probe differences in surface adsorption after thermal treatments. Nanoparticle adsorption was evaluated by NTA and BSA adsorption was assessed by CD. Both systems displayed negligible irreversible adsorption or protein denaturation, with only minor reversible nanoparticle binding and slight alterations of BSA secondary structure. In the future, both new coating technologies and different nanoparticle and biotechnological products will be considered to improve the control of drug-container interactions

    ATM kinase phosphorylates HSP90 on T297 changing its conformation dynamics and promoting its interaction with HER2 receptor tyrosine kinase

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    Heat Shock Protein 90 (HSP90) is an essential molecular chaperone whose activity is regulated not only by co-chaperones but also by distinct post-translational modifications. Interestingly, its chaperone activity is essential for the stability of several oncogenes, among which the receptor tyrosine kinase HER2. HER2 is overexpressed in 20–30% of breast and ovarian cancers. Its overexpression triggers proliferative and transforming pathways aberrant activation and therefore frequently correlates with invasive and poor prognostic features, and associates with shorter patient survival. Of note, HSP90 inhibitors have been studied in HER2-positive breast cancer and have shown promising results. Unexpectedly, we previously reported that ATM promotes the interaction of HER2 with HSP90 therefore sustaining HER2 protein stability and tumorigenicity. To further investigate the interplay between HER2-HSP90 and ATM, we tested the hypothesis that ATM could phosphorylate HSP90. We confirmed that ATM activation can induce the phosphorylation of HSP90 in HER2 positive breast cancer models. Point mutagenesis showed that T297 is the major site targeted by ATM kinase and importantly the unphosphorylatable mutant HSP90-T297A displays a reduced ability to interact with HER2, and to prevent its ubiquitination and degradation. Consistently, the overexpression of HSP90-T297A impinges on the viability of HER2-overexpressing cells, further supporting a role of this phosphorylation in the modulation of HER2 tumorigenicity. T297 is located in the middle domain of HSP90, a region that is involved in the interaction of HSP90 with clients. Consistently, structural studies indicate that T297 phosphorylation can indeed favor the chaperone's interaction with HER2, further supporting our hypothesis

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