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Circulating lncRNAs Remark Expression Profile of Cerebrovascular Malformation Endothelial Cells
Among cerebrovascular malformations, brain arteriovenous malformation (bAVM) and cerebral cavernous malformation (CCM) primarily affect microvessels. Brain AVM originates from arterioles due to impaired expression of endothelial differentiation markers, whereas CCM arises due to aberrant sprouting angiogenesis. Recent advances in the field of lncRNAs have linked perturbations of the competitive endogenous RNA (ceRNA) lncRNA-miRNA-mRNA axis to the development of several pathological conditions. However, this mechanism remains poorly investigated in cerebrovascular phenotypes. Based on RNA-seq data and enrichment analysis, we identified lncRNA genes differentially expressed in endothelial cells (ECs) isolated from bAVM and CCM biopsies. We isolated RNA from both ECs and blood samples of larger patient cohorts. By quantitative real-time PCR, gene expression was compared between pathological ECs and human brain microvascular endothelial cells (HBMECs) and between blood samples of patients and healthy controls. We identified five lncRNA genes, MIR497HG, RMST, SNHG6, SOX2-OT, and ZSCAN16-AS1 overexpressed in both ECs and blood samples of bAVM patients. In CCM ECs, FGD5-AS1 and SNHG12 were upregulated and XIST, NORAD, SNHG29, and LINC0066 down-expressed. These lncRNAs act as molecular sponges for miRNAs targeting transcripts associated with the onset of the respective phenotypes. Specifically, arteriovenous differentiation and vascular smooth muscle cell function were the two most enriched pathways related to the bAVM phenotype. For the CCM condition, the most enriched pathways included Rho-GTPase, Delta-Notch, and VEGF signalling. These data suggest a novel investigation field to better elucidate the differences in the pathogenesis, differential diagnosis, and potential therapeutic strategies for bAVM and CCM phenotypes
Exploitation of the Antibacterial Activity of Micromeria graeca L. Extracts From Northern Morocco
Micromeria graeca L. is an aromatic plant rich in bioactive molecules with potential antimicrobial properties. This study evaluated the antibacterial activity of extracts obtained using different solvents and extraction techniques. Among the tested samples, the methanolic ultrasound-assisted extract (MGME-UAE) exhibited the strongest bactericidal effect, selectively inhibiting Proteus mirabilis (inhibition zone 12.7 ± 0.6 mm; minimum inhibitory concentration [MIC] = 6.25 mg/mL). Liquid chromatography coupled with photodiode-array and electrospray ionization–mass spectrometry (LC–PDA/ESI–MS) profiling revealed sagerinic acid (30.37 ± 0.70 mg/g), 5-caffeoylquinic acid, and caffeic acid as major constituents. Mechanistic assays showed that MGME-UAE increased membrane permeability, causing significant leakage of DNA/RNA and proteins, which was further confirmed by scanning electron microscopy (SEM) visualization of cell wall disruption. These findings highlight M. graeca as a promising source of natural antibacterial agents, particularly against P. mirabilis
Approccio One Health allo studio dei virus enterici ed epatici del cane: nuovi modelli di studio nell'interfaccia uomo-animale
La crescente presenza di cani in ambito domestico e della necessità di gestione di questa specie animale in ambito urbano/sub-urbano rende necessaria una maggiore attenzione all’interfaccia che connette uomo ed animali e di perseguire gli obiettivi di sorveglianza e di controllo delle malattie attraverso un approccio One Health. Infatti, anche gli animali da compagnia possono rappresentare fonti di infezioni zoonotiche, fungere da ospiti intermedi tra specie animali e l’uomo, o essere considerate specie sentinella per la sorveglianza delle malattie emergenti. Attraverso un modello di studio biomolecolare multi-target dei virus classici (CPV-2, CAdV-1 e -2, CDV, CCoV) ed emergenti (NoV ed altri calicivirus, RoV, HEV, AstV) a tropismo enterico o epatico del cane, la presente tesi di dottorato ha avuto l’obiettivo di aggiornare i dati sui ceppi circolanti, valutare le correlazioni genomiche tra i virus del cane e quelli potenzialmente rilevanti nella specie umana. È stato adottato un approccio basato sull’analisi biomolecolare dei genomi virali e dei dati ad essi associati, comparandoli con quelli disponibili in database internazionali, in relazione ai segni clinici o a lesioni d'organo, all'origine dei campioni ed alla rappresentatività temporale. I risultati hanno descritto la circolazione dei virus target nella popolazione canina, evidenziando il ruolo dei cani quali sentinelle per lo studio della loro epidemiologia ed evoluzione. Tra i risultati più rilevanti, quelli riguardanti l’evidenza di agenti zoonotici (norovirus, astrovirus e rotavirus) e le loro correlazioni con i ceppi da altre specie animali. Nel suo complesso, questo studio fornisce un contributo nella caratterizzazione multi-target di virus rilevanti per la specie e potenzialmente rilevanti nell’interfaccia uomo-animale, offrendo un modello di studio per la comprensione del ruolo degli animali da compagnia secondo una prospettiva coerente con l’approccio One Health.The growing presence of dogs in domestic environments and the need to manage this animal species in urban/suburban environments, makes it necessary a greater attention to the human-animal interface and to promote the objectives of disease surveillance and control through a One Health approach. Indeed, even pets can represent sources of zoonotic infections, act as intermediate hosts between animal species and humans, or be considered sentinel species for the surveillance of emerging diseases. Through a multi-target biomolecular study model of classical (CPV-2, CAdV-1 and -2, CDV, CCoV) and emerging (NoV and other caliciviruses, RoV, HEV, AstV) enteric or hepatic tropism viruses of the dog, this doctoral thesis aimed to update the data on circulating strains, evaluate the genomic correlations between dog viruses and those potentially relevant in the human species. An approach based on the biomolecular analysis of viral genomes and associated data was adopted, comparing them with those available in international databases, in relation to clinical signs or to organ lesions, the origin of the samples and their temporal representativeness. The results described the circulation of target viruses in the canine population, highlighting the role of dogs as sentinels in the study of their epidemiology and evolution. Among the most notable findings were those regarding the presence of potentially zoonotic agents (noroviruses, astroviruses, and rotaviruses) and their correlations with strains from other animal species. Overall, this study contributes to the multi-target characterization of species-relevant and potentially relevant viruses at the human-animal interface, offering a study model for understanding the role of companion animals from a perspective consistent with the One Health approach
Spatial-Temporal Simulation of Routes Connecting Containers Ports
Ports are crucial in global trade, and shipping trade is relevant for all industries. Even more so now that we are experiencing political and social stresses, a situation which means that maritime routes are increasingly less safe and economically more expensive. Inefficiency emerged as a fundamental factor in the competitiveness of a maritime terminal, and research on container ships plays a relevant role in understanding and assessing the competitiveness of the infrastructure. Consequently, the time elapsed between entering and leaving the port can express the capacity of the infrastructure to handle loading and unloading operations, thus representing a measure of receptiveness. Obtaining detailed data for different ports requires a deep understanding of ship turnaround time, workloads at the yard, and company priorities, thus relying on direct interviews with port workers. Due to the exploratory nature of the study and to overcome the costly and time-consuming on-field surveys, this paper analyzed the performance through a simulation process. As input, typical waiting and handling time probability curves for major container ports are derived from a large dataset of Automatics Information Systems, and some of the most crowded and longest commercial routes are analyzed to evaluate route performances in terms of exchanged numbers of containers, waiting time at the anchoring, and berth operations. The proposed framework involves multiple steps concerning (i) possible route stops, (ii) berth occupation, and (iii) route speed variation with the final goal of reducing the loss of time and increasing the exchanged number of containers for the terminal
Age-Dependent Changes in Thermo–Viscoelastic Properties of Human Brain by Non-Equilibrium Thermodynamics with Internal Variables
Over the years, neurons undergo functional changes initially linked to the maturation of the
brain and then are progressively linked to normal aging. The curious relationship between
brain decay, aging, and neuronal diseases has aroused the interest of numerous studies to
better understand and contrast the evolution of these pathologies. The objective of this
research is to apply the non-equilibrium thermodynamic theory with the internal variables
of the study of the rheological properties of the brain, focusing on the study of viscoelastic
properties. After a thermodynamic introduction of the principal rheological phenomena,
this paper discusses the results by the application of our mathematical technique, which
revealed a prevalence of anelastic properties in the old central nervous system compared to
the young one. Furthermore, the entropy production trend tested identifies a greater disorder in the young brain in respect to the old one. The results obtained highlight that a lower
stiffness in the old central nervous system may be interpreted with dendritic regression
associated with neuronal death, both being potential consequences of an increased production of free radicals due to reduced antioxidant defenses and/or an altered mitochondrial
dysfunction in aging
Chemical Characterization of Phenol-Rich Olive Leaf Extract (Olea europaea L. cv. Ogliarola) and Its Neuro-Protective Effects on SH-SY5Y Cells from Oxidative Stress, Lipid Peroxidation, and Glycation
Live Tenebrio molitor larvae as a dietary supplement for post-weaning piglets: effects on performance and health under diets with different crude protein levels
Introduction: Weaning represents one of the most critical phases in pig production, as it is often characterised by a transient period of fasting that can impair gut integrity and ultimately reduce growth performance while increasing susceptibility to disease. At the same time, increasing pressure to reduce dietary crude protein and reliance on conventional protein sources has highlighted the need for feeding strategies that support the sustainability of feed formulations and animal health.
Aim: This study evaluated the effects of daily supplementation with live Tenebrio molitor larvae on performance, feed intake, health status, digestibility and metabolic markers in post-weaning piglets fed diets containing moderate (15%) or standard (17%) crude protein levels.
Methods: A total of 48 piglets were allocated to four treatments: control diets without larvae (CTRL15 and CTRL17) and corresponding diets supplemented daily with 50 g/pig/day of live mealworm larvae (INS15 and INS17). Growth performance, feed intake, feed efficiency, time required to consume the larvae, health indicators, apparent total tract digestibility, serum biochemical parameters, antioxidant capacity and mineral profile were assessed over a 42-day trial.
Results and discussion: Larvae supplementation significantly improved early feed efficiency and growth performance (p < 0.05), particularly during the first weeks post-weaning. Piglets in INS17 achieved higher final body weight compared with CTRL groups (p < 0.05), while INS15 piglets reached performance comparable to CTRL17, despite the lower dietary protein level. Live larvae were rapidly and consistently consumed from the moment of supplementation, with consumption time decreasing below 2 min during days 30–42 of the trial, whereas soybean meal supplementation elicited lower feeding interest in piglets with longer consumption time. Larvae supplementation was associated with an improved health status, including a lower incidence of diarrhoea, reduced occurrence of respiratory disorders and higher vitality scores compared with control groups (p < 0.05) throughout the trial. No differences were observed in nutrient digestibility, serum metabolic profile and antioxidant status at day 42.
Conclusion: In conclusion, live T. molitor larvae represent a promising functional feeding strategy to stimulate early feed intake during weaning and enhance piglet resilience, supporting growth performance and health while allowing dietary protein levels to be moderately reduced without negative effects
Selected Nutraceuticals in Metabolic Syndrome: Molecular Mechanisms and Clinical Implications
In recent years, there has been a growing scientific and clinical interest in nutraceuticals, bioactive compounds derived from natural sources such as plants, fruits and cereals. These substances have gained prominence due to their diverse pharmacological properties, particularly their anti-inflammatory, antioxidant and antitumor activities. In addition, scientific evidence supports their beneficial role in the prevention and management of cardiovascular diseases, which represent the principal focus of the present review. This review provides a comprehensive and detailed analysis of selected nutraceuticals related to the metabolic syndrome, a multifactorial pathological condition characterized by a cluster of metabolic disturbances that collectively increase the risk of developing cardiovascular disease and type 2 diabetes. The metabolic syndrome is typically defined by the presence of abdominal obesity, insulin resistance, hypertension and dyslipidemia, which includes elevated plasma triglyceride levels and decreased concentrations of high-density lipoprotein (HDL) cholesterol. Given the global importance and prevalence of metabolic syndrome, identifying new strategies to treat these disorders, such as the use of nutraceuticals, has become a central focus of biomedical research
A Multidimensional Approach to Support Industrial Symbiosis: Reuse of Olive Oil Mill Wastewater in Bread Production
Industrial Symbiosis (IS) represents a key strategy within the Circular Economy (CE) paradigm, enabling firms located near enhance competitiveness through the collective exchange and valorisation of resources. By fostering the reuse of water, energy, and materials, IS contributes to the sustainable optimization of manufacturing processes. Nevertheless, the implementation of IS, as a distinct business model, requires the active collaboration of heterogeneous stakeholders, which often generates critical challenges in aligning interests and achieving equitable benefits. This study explores an innovative approach to agri-food symbiosis by evaluating the incorporation of Olive Oil Mill Wastewater (OOMW), a by-product of olive oil production, into bread formulations. This strategy not only mitigates the environmental burden associated with OOMW disposal but also promotes resource efficiency within the olive oil supply chain. Bread samples were produced by varying the concentration of OOMW, and each formulation was assessed according to quality characteristics, consumer acceptability parameters, and sustainability aspects. The selection of the best-performing formulation was conducted through a Multi-Criteria Decision-Making (MCDM) framework, specifically applying the VIKOR method. The findings highlight how the integration of OOMW into bread production can generate a dual benefit, improving food quality while advancing sustainable practices in both the olive oil and bakery sectors
The role of cleft flexibility in tetracationic oxacalixarenes-paraquat recognition revealed by experimental and ab initio molecular dynamics investigations
Molecular recognition in aqueous environments depends on a subtle interplay of non-covalent interactions, solvent effects, and entropic contributions. Herein, we report a combined 1H NMR and ab initio molecular dynamics (AIMD) study on paraquat (PQT2+) recognition by two isomeric tetraoxacalix[4]arenes bearing four ammonium groups. Despite their comparable charge and cavity architecture, only the more flexible all-meta-bridged 4,6,16,18-tetraammonium-2,8,14,20-tetraoxacalix[4]arene (1·H44+) isomer forms a stable complex with PQT2+ in water, whereas the more rigid, ortho-meta-ortho-meta-bridged 4,6,17,19-tetraammonium-2,8,15,21-tetraoxacalix[4]arene (3·H44+) ejects the dication from its cleft. Our ab initio simulations reveal that cavity adaptability and solvent-mediated effects dictate the binding behavior, with correlation analyses highlighting stronger angular-distance anticorrelations in the 3·H44+/PQT2+system, revealing that host-guest complexation is largely entropy driven