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Evaluation of Antioxidant and Anti-Inflammatory Effects of a Nanoformulation Derived from Annurca Apple Callus Extract in an In Vitro Model of Iron Overload-Induced Inflammation
Get PDFFerroptosis, a regulated form of cell death driven by iron accumulation and lipid
peroxidation, contributes to oxidative stress-related skin damage. This study evaluates the
antioxidant and anti-inflammatory effects of a nanoformulation derived from an Annurca
apple callus extract in an in vitro model of ferroptosis using human keratinocytes (HaCaT
cells). A hydroalcoholic extract from light Annurca apple callus (LCE) was nanoformulated
with Pluronic® F127 and Soluplus® to enhance stability and bioavailability. The
resulting nanoformulation (NF-LCE) exhibited optimal particle size (103.17 ± 0.87 nm),
polydispersity index (0.21 ± 0.00), and zeta potential (−1.88 ± 0.64 mV). Iron overload
(100 μM) was employed to induce oxidative stress and inflammation in HaCaT cells, resulting
in elevated levels of inflammatory markers (COX2, IL-6, TNF-α) and a diminished
antioxidant response, as indicated by decreased expression of GPX4 and Nrf2. NF-LCE
treatment restored GPX4 and Nrf2 levels (~0.8-fold increase, p < 0.05) while significantly
reducing COX2 (36.6%, p < 0.01), IL-6 (79.6%, p < 0.0001), and TNF-α (30.9%, p < 0.1). These
results suggest NF-LCE as a promising therapeutic strategy for mitigating ferroptosisinduced
skin damage, warranting further investigation in advanced skin models and
clinical applications
Cognitive cerebellum dominates motor cerebellum in functional decline of older adults with mild cognitive impairment
Get PDFObjectives: The present study aims to investigate the role that cognitive cerebellar lobules, compared to the motor ones, could have on performance abilities control in older individuals with Mild Cognitive Impairment (MCI). Methods: Thirty-six participants with MCI were retrospectively recruited from the outpatient clinic for Cognitive Decline and Dementia at Geriatric Clinic and Regional Center for Brain Aging. Cognition was assessed through a reaction time (RT) task in which a mere cognitive (COG) component (RT/S1 COG, RT/S3 COG) has been isolated from a motor (MOT) component (RT/S1 MOT, RT/S3 MOT). Performance abilities were evaluated using Short Physical Performance Battery (SPPB), Tinetti Scale, and Activities of Daily Living (ADL). Finally, structural neuroimaging was conducted using magnetic resonance imaging at 3T. Results: Left_Crus_I showed a correlation with SPPB, ADL%, and RT/S3 COG. Vermis_VI and Right_VI were correlated to ADL%, and RT/S3 COG with the entire lobule VI. ADL% showed negative correlations with RT/S1 COG, RT/S3 COG, and RT/S3 MOT. In the regression analysis, the strongest associations were found between RT/S3 COG and SPPB gait speed (R2 = 0.44, p = 0.03), Tinetti gait speed (R2 = 0.62, p < 0.001), and ADL% (R2 = 0.78, p < 0.001). Regarding cerebellar volumes, Right_Crus_I was associated with all SPPB tests, while Left_VI was associated with functional autonomy (ADL%: R2 = 0.78, p = 0.04). No associations were found between performance variables and total intracranial volume. Conclusions: This study highlights that the cognitive cerebellar component dominates over the motor one even in the control of physical and functional capabilities of older adults with MCI
Exploring intranasal delivery of peptide and protein nanoparticles by a thermoresponsive hydrogel
Get PDFEffective delivery of peptide or protein-based drugs (PPDs) remains a challenge as parenteral routes are invasive and PPDs are subjected to enzymatic degradation via the oral route. As such, intranasal (IN) route is an effective, non-invasive approach for delivering PPDs locally, systemically, and to the central nervous system (CNS), while maintaining the stability of the drugs. The study investigates the potential of a novel thermoresponsive polymer (PNPHO), as a carrier to facilitate IN delivery of peptides/proteins. Two types of nanoparticle formulations (Low-F and High-F) using a low and a high PNPHO concentration (20 mg/mL and 35 mg/mL) were prepared with bovine serum albumin (BSA) incorporated in it. Both formulations exhibited good physicochemical properties in terms of particle size (Low-F: 29 nm; High-F: 39 nm), polydispersity index (PDI) (<0.3) and zeta (ζ) potential (−3 to −6 mV) with a high encapsulation efficiency (EE) (86 %–96 %) maintained at 4 °C during a 4-week stability study. High-F formulation demonstrated a significantly greater aerosol drug deposition in the entire nasal cavity and in the olfactory region in vitro compared to free BSA at 45° spray angle. Both formulations were found to be non-toxic when tested on nasal epithelial cell lines. Importantly, a significant increase in transepithelial resistance was observed for the nasal epithelial cells post 4 h treatment with High-F along with a significant reduction in BSA transport across the cells compared to free drug, indicating tightening of cellular junctions and prolonged drug residence time owing to its mucoadhesive property. Altogether, the findings suggest that PNPHO polymer is a potential carrier for targeted delivery of peptide/protein using the IN route
Circulating Neuronal Exosome Cargo as Biomarkers of Neuroplasticity in Cushing's Syndrome
No full textThe hippocampus is the main target of glucocorticoids (GCs) in the brain since it contains the greatest concentration of the specific receptors. GCs are among the factors modulating adult hippocampal neurogenesis (AHN), which occurs in mammalians, including humans. Prolonged exposure to high GC levels triggers AHN impairment and induces affective and cognitive deficits, consistently with hippocampal neurogenesis functions. Cushing's syndrome (CS) is a rare endocrine disorder characterized by persistently elevated GC levels, namely, cortisol, that also results in affective disorders and impairment of hippocampus-associated memory, suggesting a disruption of hippocampal neurogenesis. Players of adult neurogenesis process, such as Neural Stem/Progenitor Cells and differentiating neuronal cells, release exosomes able to cross brain blood barrier, reaching the peripheral blood. MicroRNAs are known to be selectively enriched in neuronal exosomes and to play a crucial role in adult neurogenesis regulation. The main question addressed in this exploratory study was whether neuroplasticity-related microRNAs (miRNAs), carried by neuronal-derived exosomes in peripheral blood, could reflect alterations in neurogenic processes associated with Cushing's syndrome. Hence, in the present work, we measured the content in selected miRNAs of neuronally derived exosomes in peripheral blood of patients affected by endogenous and active CS and age and sex-matched healthy subjects. The human miRNAs (miR-126, miR-9, miR-223, miR-34a, miR-124a, and miR-146a) were quantified by RT-qPCR. All the miRNAs analyzed were significantly differentially expressed in CS patients as compared to healthy subjects. Our findings support the following: (i) patients with Cushing's syndrome (CS) may exhibit a putative dysregulation of neurogenesis that could underlie the early-onset impairment of affective and cognitive functions; (ii) the exosomal cargo may represent a potential biomarker for monitoring functional and dysfunctional neuroplasticity processes in adult humans. Additional studies are needed to confirm and expand upon the findings across a wider cohort of patients
Ricordo di Valeria Purcaro
No full textValeria Purcaro, archeologa e professoressa presso l’Università degli Studi di
Urbino per un quarantennio, è stata una di quelle persone che non si dimenticano.
La sua cultura, la sua affabilità, la sua serietà, la sua professionalità e la sua
estrema bontà sono solo alcune delle qualità che la contraddistinguevano. Subito
dopo la sua repentina e inaspettata scomparsa, come Centro Studi Vitruviani,
ente di cui era vicepresidente, abbiamo pensato di dedicarle una giornata di studi
incentrata sui temi di cui si era occupata durante tutta la sua attività scientifica:
innanzitutto Fano, dall’età romana all’età moderna, poi il territorio marchigiano
attraversato dalla via Flaminia e infine Cirene, la colonia greca in terra di Libia
in cui si era formata, insieme a tanti colleghi dell’ateneo urbinate, come membro
della missione diretta da Sandro Stucchi
Spatial regimes in heterogeneous territories: The efficiency of local public spending
Get PDFWe study the impact of spatial heterogeneity on cost efficiency in Italian municipalities, introducing an original method to identify functionally homogeneous territorial areas that differ from existing administrative boundaries. Our method incorporates territorial and geographical dimensions, including latent variables associated with spatial heterogeneity—relevant factors yet often overlooked in previous empirical studies. Using spatial data on road and territory planning services, we identify clusters of municipalities with shared characteristics and measure their relative efficiency within these clusters. Our findings reveal marked territorial disparities in cost efficiency, challenging conventional one-against-all benchmarking methods. Unlike standard approaches that compare each municipality with all others, our method offers a more accurate basis for evaluating municipal performance and informing policy decisions on services to citizens. This contributes to a more effective and equitable allocation of public resources, addressing practical and methodological limitations in the existing literature
Distributing intelligent functionalities in the Internet of Things with agents and Digital Twins
No full textAutonomous Agents (AAs) and Digital Twins (DTs) are two widely used abstractions in the literature about the engineering of “intelligent” Internet of Things (IoT) systems and applications. However, their role can be considered partially overlapping given the fragmented landscape of approaches emerging from the literature. There, in fact, either AAs or DTs, or their combination, are sometimes used for achieving the same goals. In this paper, we attempt to clarify similarities and differences of these abstractions and argue that the choice to use AAs or DTs (or an integration of the two) should stem from a principled analysis of the IoT system requirements. That is, by matching the desired intelligent functionalities with the properties of the two abstractions to find the most appropriate one. Accordingly, we (i) analyse the state-of-the-art approaches to identify how AAs and DTs are currently used to encapsulate and distribute intelligent functionalities across IoT system components; (ii) propose a set of principles to assist designers in choosing the most suitable abstraction for a given functionality; and (iii) discuss exemplary architectures that may arise from applying such principles. To conceptually validate our contribution, we analyse the practical case of an intelligent manufacturing system and show how following the outlined principles leads to interesting properties in the final system design
Pindar and Tragedy: A Fresh Look at Dochmiac in Choral Lyric
No full textThis study addresses the question of the presence of dochmii in choral lyric poetry, a topic that has been the subject of considerable discussion in the second half of the last century. The ancient colometric paradosis provides substantial confirmation of the use of dochmii in the lyric-choral songs of the classical age, with a notable prevalence in the latter quarter of the fifth century BCE. The period coincides with the rise of Aeschylus at the court of Hieron and the mutual relations between numerous musicians at the prestigious Sicilian seat. The striking increase in the use of dochmius in lyric-choral authors (and in Pindar, in particular) could be explained in the light of emulation of tragic art in the dynamic context of the Syracusan court
Insights From 7 Years of CodyMaze Experiments
No full textThroughout the years, many code literacy initiatives have focused on games for children that illustrate the fundamental programming concepts in an abstract fashion. Many of these game-like educational tools, influenced by the popular "Hour of Code" web game, are based on grid-based movements that are well-suited both for digital activities and for physical games with multiple participants.
CodyMaze is an educational game, first developed in 2017, that combines physical movement with basic programming concepts to develop computational thinking. Players navigate a virtual maze overlaid on a real-world 5x5 grid, where each cell contains a QR code. By scanning these codes and following instructions, players move through the maze, executing sequences of commands that introduce programming constructs with growing complexity.
The game is designed to be played on a large scale grid, which can be represented in a variety of ways, such as tape on the ground or cardboard boxes. Players move from one cell to another in order to reach their next destination, which is provided as a sequence of instructions that must be followed correctly in order to advance. This setup encourages active participation and helps players understand programming logic in an engaging manner. CodyMaze has been utilized in various educational settings, including schools and public events, to promote coding literacy among students and the general public.
In response to the COVID-19 pandemic, adaptations of CodyMaze have been made to facilitate at-home or classroom play. For instance, Mirabilandia, an amusement park in central Italy, collaborated to create a version of CodyMaze that can be set up in schools or homes, providing downloadable kits and a dedicated app to recreate the experience outside the park. Thematic versions were developed, among others, for INAF and to support the Neoconnessi digital literacy campaign.
In this paper we discuss the evolution of CodyMaze throughout the past years, we describe noteworthy installations and events, we present the features of the new CodyMaze web app, and we discuss usage statistics from the last 4 years