Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

University of Modena and Reggio Emilia

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia
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    Lipidic nanomedicines enhance Hinokitiol activity on human primary macrophages from Ferroportin disease patients

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    Iron overload disorders pose complex clinical challenges. Hinokitiol (HK) is a promising therapeutic candidate as it can shuttle iron across cell membranes and release sequestered intracellular iron, especially for conditions like Ferroportin Disease (FD), where phlebotomy and iron chelation are often inadequate or burdensome. However, HK's clinical utility is limited by its physical-chemical properties and biodistribution. In this study, we report the first evaluation of biodegradable and biocompatible Nanomedicines (NMeds) developed for the parenteral administration of HK. Polymeric and lipidic NMeds were evaluated, namely poly lactic-co-glycolide (PLGA), Cholesterol (Chol) NMeds, and Nanostructured Lipid Carriers (NLC). The optimization led to homogeneous NMeds with size < 300 nm and encapsulation efficiency up to 40 %, despite the small molecular weight and volatile nature of HK. Drug retention ability was assessed, allowing for the selection of 3 NMeds to be tested on iron-loaded macrophage model (J774 cell line) and human primary macrophages obtained from healthy blood donors and FD patient-bearing two different mutations. Data revealed that all HK-loaded NMeds are non-toxic and can accumulate in the cells, but most importantly they are more efficient than the free HK in reducing the intracellular iron pool. NLCs in particular showed the most promising behavior in terms of high efficacy and low toxicity. These results demonstrate that delivering HK via NMeds is preferable to administering free HK, representing the first step towards the development of a more efficient treatment of this currently challenging disease

    Insurance and Social Theory

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    Maximizing high-value biomass in Scenedesmus and Chlorella: Exploring light-driven macromolecular storage for nutraceutical and feed applications

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    The stringent safety requirements for using microalgal biomass in the pharmaceutical, food, and feed industries demand increased scientific research to identify optimal cultivation conditions under axenic environments. To achieve high biomass yields and macromolecular productivity, various cultivation parameters must be systematically evaluated. In particular, the strain-specific responses to these conditions underscore the importance of understanding how inorganic carbon supply and light irradiation influence biomass proliferation and macromolecular accumulation. To gain deeper insight into microalgae productivity, Scenedesmus sp. and Chlorella sp. were cultivated under axenic condition with a 2 % CO2 supply. The effects of different light wavelengths (red, green and blue) and light intensities (ranging from 80 μE to 200 μE) were investigated. The highest biomass production for Scenedesmus sp. was observed under red, green, and blue light at an intensity of 200 μE, yielding 0.78 ± 0.12 gL-1, 0.94 ± 0.07 g L−1, and 1.00 ± 0.10 g L−1, respectively. Red, green, and blue light at 150 μE intensity increased lipid storage to 25.32 ± 1.50 %, 39.36 ± 1.81 %, and 33.91 ± 19.87 %, respectively. In contrast, the biomass of Chlorella remained stable under 100 μE of red, green, and blue light, producing 0.65 ± 0.04 g L−1, 0.66 ± 0.09 g L−1, and 0.66 ± 0.07 g L−1, respectively. Increasing light intensity did not significantly affect lipid storage, which remained at 6.87 %. Protein content was consistent in both microalgae strains across all experimental conditions, exceeding 15 %. Lipid characterization revealed a high concentration of oleic, palmitic, stearic, and vaccenic acids, highlighting the potential for integrating these microalgae strains into the pharmaceutical, nutraceutical and feed industries

    Microbiota-gut-brain axis dysregulation in Alzheimer’s disease and its modulation through probiotic supplementation

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    The microbiota-gut-brain axis (MGBA) has been implicated in the pathophysiology of Alzheimer’s Disease (AD).Probiotics reduced the progression of ADin different mouse models, possibly through MGBA modulation, but human data are still limited. Here, we evaluated whether differences in the gut microbiome (GM), pro-inflammatory markers and other MGBA mediators were associated with probable AD (pAD). We also assessed the impact of a 12-week probiotic treatment on MGBA. Forty-five pAD patients and 47 healthy subjects (HC) were recruited at IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli of Brescia (Italy). An uncontrolled clinical investigation was performed to test the effects of 12-week probiotic supplementation in the pAD group. Fecal microbiota composition, intestinal and blood inflammatory markers, and microbiota-related metabolites were assessed before supplementation in all participants and after only in pAD. pAD patients showed intestinal inflammation, an altered GM profile, blood changes in the tryptophan metabolism, and reduced glutamate levels compared with HC (p-value < 0.049). Probiotic supplementation partially modulated these alterations, determining a reduction in several pro-inflammatory mediators, and an increase of GM-related protective factors, such as butyrate (p-value < 0.040) in pAD. These findings confirmed the presence of MGBA alterations in AD and suggested a potential beneficial effect of probiotic supplementation through modulation of GM functionality rather than composition. Further research is required to confirm these results and their clinical relevance

    Two-Dimensional Irregular Knapsack Problem with Defects from a Dynamic Textile Environment

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    The production of clothing, garments, footwear, and other related goods involves cutting fabric and leather rolls. High-quality goods must be free of defects, and the cutting process must be optimized to improve all stages. The problem emerges from a dynamic textile production environment in which a large object is first scanned for defective areas and then cut into smaller irregular items free of defects. The time to define the cutting pattern is short and depends on knowing the defects first. This paper proposes an iterated local search-based heuristic as a solution method to the two-dimensional irregular knapsack problem, which is an NP-hard problem. The algorithm starts by generating an initial random solution, which is then improved using perturbation and local search operators based on swap and insertion moves. Items are positioned in the large object with the bottom-left positioning rule. Experiments are conducted on instances from the literature, evaluating the solution quality for different time limits. The algorithm achieves satisfactory solutions from as early as a 30 s time limit, occupying an average of 75.63% of the object area. The occupied area increases as the time limit increases, reaching 77.78% on average for a time limit of 120 s

    Prevalence, distribution and associations of the scleroderma capillaroscopic patterns: new insights from the Italian SPRING-SIR registry

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    Objectives To assess the relationship between disease duration and the prevalence/distribution of nailfold videocapillaroscopy (NVC) patterns, named according to the current classification as 'early', 'active' and 'late', in a large cohort of systemic sclerosis (SSc) patients. Methods A cross-sectional analysis was conducted on 1689 patients undergoing standardized NVC. Clinical-serological data and treatments were collected. Statistical comparisons and multivariable logistic regression models were applied, including analyses based on disease duration. Results The prevalence of NVC patterns was as follows: 'early' 21.6%, 'active' 47.4%, 'late' 25.7% and normal/non-specific 5.3%. The distribution by disease duration showed that the three main patterns were always present. While the 'early' and 'active' progressively decreased (from 30.3% and 51.9% in patients with <= 5 yrs, to 14.6% and 43.5% in those >10 yrs, P < 0.01), the 'late' pattern increased from 13.2% (<= 5 yrs) to 36.0% (>10 yrs) (P < 0.001) and was associated with internal organ involvement, anti-topoisomerase antibodies and more therapies (P < 0.01). Conversely, the 'early' and 'active' patterns were associated with the limited-cutaneous subset (P < 0.01) and anti-centromere antibodies (P < 0.001). Multivariable analysis confirmed a strong association between the 'late' pattern and skin/peripheral vascular involvement. Notably, the presence of the 'late' pattern in patients with <= 2 yrs (10.9%) was significantly associated with scleroderma renal crisis (P = 0.012). Conclusion SSc-NVC patterns are not strictly time-dependent and can be observed at any stage of the disease, suggesting that microvascular damage progression is heterogeneous across different disease periods. Therefore, a revised classification of NVC changes considering both disease duration and NVC severity could improve its prognostic accuracy

    Cell line-specific modulation of inflammation by oestradiol in an in vitro model of antenatal depression

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    Antenatal depression is linked to adverse neurodevelopmental outcomes in offspring, likely mediated by a multitude of biological mechanisms, including elevated maternal cytokines. However, factors modulating fetal vulnerability or resilience to inflammatory exposure remain unclear. This study examines whether the steroid hormone, oestradiol, can modulate inflammatory responses in an in vitro model of hippocampal neurogenesis, using two fetal hippocampal progenitor cell lines: female-derived HPC0A07/03C and male-derived HIP-009. Cells were pre-treated with oestradiol for 24- and 48-hours during proliferation, followed by interleukin-1beta (IL-1β) exposure prior to the initiation of differentiation. Markers of proliferation and neurogenesis, as well as inflammatory cytokines and kynurenine pathway metabolites, were assessed. In female HPC0A07/03C cells, oestradiol pre-treatment prevented IL-1β-induced proliferation and apoptosis, and reduced cytokine production. Conversely, in male HIP-009 cells, oestradiol pre-treatment did not prevent IL-1β-induced reduction of proliferation and apoptosis and indeed enhanced inflammatory responses after 48 h. In terms of differentiation, IL-1β produced opposite effects on neurogenesis across cell lines, increasing neuronal maturation in female HPC0A07/03C cells, but decreasing neurite complexity in male HIP-009 cells. Notably, oestradiol pre-treatment in both lines reduced neuronal differentiation and increased kynurenine levels, suggesting potentially detrimental long-term effects. These results highlight complex, potentially cell-line-dependent, sex-specific hormone-immune interactions shaping fetal neurodevelopment and underscore the need to investigate these interactions when assessing risks and developing therapeutic interventions for inflammation-related neurodevelopmental disorders

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    Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia is based in Italy
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