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    Effects of hydrogen peroxide on slow- and fast-growing NIH/3T3-derived cultures: nuclear and cytoplasmic aspects related to senescence and transformation

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    Cellular senescence can occur with similar phenotypes in normal cells, during aging, and in tumor cells, spontaneously or after cytostasis. The fall or increase in proliferative activity are key aspects of the respective conditions, in which the levels of reactive oxygen species can vary, affecting the cellular redox homeostasis. This work aimed to study the relationships between senescence and transformation by comparing cells with different proliferative activities and phenotypes attributable to transformation (NIHs cultures) or senescence (NIHv cultures), before and after incubation with hydrogen peroxide. Both cultures were derived from the NIH/3T3 cell line, which was used here as a reference (NIHb), after the serum starvation. Our experimental model can be representative of the heterogeneity of cell subpopulations, with different degrees of transformation and senescence, found in some tumors. The characterization of the functional properties of NIHb, NIHs, and NIHv cells was performed by a morphocytometric analysis of the cell cycle progression, mitochondrial and lysosomal content/activity, and superoxide anion production. The efficiency of the lysosomal compartment was also assessed by estimating the autophagic activity and measuring lipofuscin autofluorescence. Comparisons of nuclear and cytoplasmic parameters before and after the incubation with hydrogen peroxide revealed differences in the expression and modulation of cellular senescence patterns. The treatment effects were very limited in the NIHb culture; the senescence condition was essentially maintained in the NIHv cells, while the most relevant changes were found in the NIHs cells. In the latter, the acquisition of the senescent phenotype, also demonstrated by the positivity of SA-β-galactosidase, was correlated with a decrease in proliferative activity and a change in the content/activity of the mitochondria and lysosomes, which showed similarities with the basal senescence conditions of NIHv cells. In NIHs cells, increased autophagy events and lipofuscin accumulation also indicate the establishment of cytoplasmic dynamics typical of senescence. The variable responses to hydrogen peroxide, besides depending on the different basal cytokinetic activity of the cultures examined, appeared to be related to the specific cell redox state resulting from the balance between endogenous ROS and those produced after treatment. Especially in NIHs cells, the slowing down of the cell cycle was linked to dynamic interconnections between the mitochondrial and lysosomal compartments. This would indicate that transformed cells, such as NIHs, may express morpho-functional aspects and markers typical of cellular senescence, as a consequence of the modulation of their redox state

    Parasitic risks and One Health implications of valorising slaughterhouse animal by-products in raw meat-based diets for pets

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    The increasing popularity of raw meat-based diets (RMBDs) for companion animals has raised One Health concerns regarding their microbiological and parasitological safety, particularly when raw diets are used at home without following standard safety precautions. These diets may serve as a transmission route for zoonotic parasites, posing risks not only to animal health but also to human health and the environment. This study aimed to assess the parasitic risk of animal by-products (ABP's) from sheep and cattle slaughtered in Sardinia, with a focus on zoonotic parasites of veterinary and public health significance. A total of 672 sheep and 503 cattle were examined in seven slaughterhouses between March 2021 and July 2023. Organs were inspected macroscopically, with representative samples subjected to laboratory parasitological analysis. In sheep, Echinococcus granulosus was detected in 67.7 % of animals, with the liver being significantly more affected than the lungs (54.8 % vs. 49.1 %; P = 0.038). Fertile hydatid cysts were more prevalent in the lungs (9.5 %) than in the liver (5.5 %). Cysticercus tenuicollis and Dicrocoelium dendriticum were observed in 2.4 % and 14.7 % of sheep, respectively. Bronchopulmonary nematodes were detected in 44.8 % of cases, and macroscopic Sarcocystis gigantea cysts were identified in 27.7 % of examined oesophagi. In contrast, cattle showed a significantly lower parasitic burden, with E. granulosus detected in only 2.0 % of animals and fertile cysts being rare. Fasciola hepatica was found in 0.4 % of cattle livers, and no Dicrocoelium or bronchopulmonary nematodes were detected. The results demonstrate a high parasitological load in sheep-derived ABPs, reinforcing the need for strict sanitary controls before their inclusion in RMBDs. Given the zoonotic potential of the detected parasites, particularly in endemic regions, the adoption of targeted decontamination measures is essential. These findings underscore the importance of integrating a One Health approach into raw pet food safety, public health and ABP management strategies

    I costi diretti del crimine violento nei Sistemi Locali del Lavoro

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    Il capitolo esamina l’impatto economico diretto della criminalità violenta in Sardegna tra il 2018 e il 2024, con particolare attenzione alle rapine e agli attentati nei Sistemi Locali del Lavoro (SLL). Le rapine mostrano una forte concentrazione territoriale, con picchi anomali dovuti ad assalti a portavalori. Gli attentati, spesso incendiari e mirati a mezzi da lavoro e veicoli aziendali, presentano una diffusione capillare e trasversale sull’intero territorio regionale, colpendo settori produttivi strategici come edilizia, gestione rifiuti e attività turistiche, da cui si evincono matrici e dinamiche criminali differenti. L’approccio metodologico, basato su fonti giornalistiche e stime conservative, elaborate con il supporto dell’intelligenza artificiale, consente una lettura comparativa dei fenomeni, pur nella consapevolezza dei limiti informativi e della sottostima dei costi reali. L’analisi offre spunti per politiche pubbliche differenziate, orientate alla prevenzione, al sostegno delle vittime e alla resilienza economica dei territori, con particolare attenzione alle vulnerabilità locali e alla coesione sociale quale leva di contrasto

    Il pane nell’iconografia della Sardegna protostorica

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    L’analisi dell’iconografia della Sardegna protostorica ha evidenziato l’esistenza di varie rappresentazioni di pane. In particolare sono noti 27 bronzetti di offerenti con pane, che mostrano la varietà dei prodotti dell’epoca (focacce, pani ripieni, dolci), suggerendo le tecniche di preparazione e mostrando, inoltre, il valore dell’alimento e il suo legame con il sacro e con le pratiche cultuali.The analysis of the iconography of protohistoric Sardinia highlights the existence of various bread representations. In particular the 27 known bronze figurines of bread-offerers illustrate the variety of products of the era (flatbreads, stuffed breads, sweets), suggest preparation techniques, and underscore the important value of bread and its connection to the sacred sphere and cultic practices

    Global health at crossroads: uniting together to overcome challenges, restore trust and advance priorities for a sustainable future

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    The world is currently facing an unprecedented convergence of crises that threaten the core pillars of public health, scientific integrity, and social stability. These challenges are profoundly interconnected and have the potential to exacerbate global inequalities, jeopardize health security, and undermine the progress achieved through decades of international collaboration. Our viewpoint declaration, developed by 366 healthcare workers and scientists from 119 countries across six continents, highlights the urgent need for global solidarity and collective action to address these interconnected global health challenges. As healthcare workers and scientists, we must prioritize the protection of scientific integrity, combat political interference, and restore public trust in the scientific process. This will require a commitment to transparency, ethical responsibility, and evidence-based decision-making that can stand strong in the face of political and social adversity. The COVID-19 pandemic has underscored the critical importance of resilient healthcare systems, emphasizing that preparedness, capacity building and coherent leadership and coordination are essential for future global health crises. In addition, our call for a One Health approach, acknowledging the intricate relationship between human, animal, and environmental health, has never been more pressing, especially as zoonotic diseases and antimicrobial resistance spread across borders. As we confront ongoing wars, environmental destruction, and global persistent health inequalities, it is only through unity, solidarity, collaboration, and innovation that we hope to build a healthier, more equitable world. Together, we must ensure that science and medicine remain a force for good, capable of addressing both the immediate and long-term needs and challenges facing our shared future

    Abitare la soglia della fragilità tra l'essere e il divenire

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    Dual Biomolecule Recognition by Diruthenium Paddlewheel Complexes: A Combined Computational Thermodynamics and Bioinformatic Structural Analysis

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    : The development of novel metallodrugs is an important direction to address the limitations of conventional therapeutics. In this study, we investigated the dual biomolecule recognition capabilities of diruthenium paddlewheel complexes, a promising class of anticancer agents. We integrated two complementary approaches: density functional theory (DFT) calculations and bioinformatic structural analysis. Our DFT calculations characterized the thermodynamic feasibility of axial ligand substitution by key protein nucleophiles, namely cysteine (Cys), histidine (His), and adenine, while also probing the resulting structural motifs, including the effect on the ruthenium-ruthenium (Ru─Ru) bond distance. This analysis revealed the energetic spontaneity of complex formation with these nucleophiles and, notably, a nuanced flexibility of the Ru─Ru core that accommodates diverse ligand combinations. Subsequently, the computationally derived geometric assets were utilized to perform a comprehensive motif search within the Protein Data Bank (PDB) database. The PDB screening successfully identified the presence of these motifs, particularly Cys-His, Cys-Cys, and His-His, within numerous protein structures, including several clinically relevant targets. This work confirms the potential of the diruthenium paddlewheel complex as a multitargeting agent and establishes a robust, integrated methodology for the rational design and prevalidation of such metallodrugs by bridging atomic-level theoretical understanding with real-world biological structural data

    Senza parole. L’arte narrativa del Fumetto Muto

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    Measuring the Effects of the Commonest Exercise Programs on Subjective Fatigue in People with Multiple Sclerosis: A Randomized Effectiveness Trial

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    Purpose: To test and compare the effects of the four most common exercise-based interventions employed to manage subjective fatigue and functional impairments due to multiple sclerosis (MS). Methods: Persons with MS (PwMS) complaining of fatigue as main symptom were enrolled. After a comprehensive baseline assessment evaluating subjective fatigue impact and severity (primary endpoints), quality of life, cardiorespiratory performance and mobility and motor-functional outcomes, participants were randomly assigned to an eight-week intervention consisting of strength (ST) or aerobic training (AT) or strength+aerobic (Combo) or global rehabilitation (Rehab). Results: Sixty-two mildly-moderately disabled PwMS (median EDSS 3.5±1.6; age 46.6±11.8 years; 75% women) completed the study. No adverse events were reported. Between-group comparisons did not detect significant differences among groups. Considering training-induced effects separately for each group, AT showed the largest reduction in the Fatigue Severity Score (-18.8%; -0.81 pts, CI: -1.53, -0.09, p=0.03) followed by ST (-16.8%; -0.84 pts, IC: -1.56, -0.12, p=0.02). Fatigue impact assessed by MFIS was significantly reduced after AT (-35.3%; -12.44 pts, CI: -19.00, -5.87, p<0.01), followed by Combo (-33.8%; -13.36 pts; CI: -20.38, -6.34, p<0.01) and Rehab (-26.2%; -8.18 pts; CI: -16.10, -0.26, p=0.04). Regarding motor-functional outcomes, beyond the expected training-specific effects (e.g., muscle strength gains following ST, increased cardiorespiratory fitness following AT), comfortable and fastest walking speed increased significantly following Rehab (+0.16 m·s -1, CI: 0.08, 0.23, p<0.01; +0.22 m·s -1, CI: 0.11, 0.329, p<0.01, respectively) exceeding established thresholds for clinically important changes. Also the increased distance covered in six minutes was found to exceed clinically importance thresholds following ST (+55 m, CI: 9.15, 101.02, p=0.02) and Combo (+62 m, CI: 14.04, 109.13, p=0.01). Conclusions: Although the superiority of one treatment over the others has yet to be claimed and all interventions proved beneficial to reduce fatigue impact, only AT and ST reduced both fatigue severity and impact, with the former intervention associated with the largest within-group effect sizes. When testing the effects of interventions on mobility outcomes, AT led to the largest improvements, followed by Combo

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