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Tomato and Olive Bioactive Compounds (TOBC) Promote Regeneration by Modulating Inflammation in Zebrafish and Human Epithelial Cells
Inflammation is a key determinant of tissue regeneration, where its timing and resolution dictate the success of repair. Tomato and Olive Bioactive Compounds (TOBC) is a patented nutraceutical derived from tomato and olive mill wastewater, rich in polyphenols such as lycopene and hydroxytyrosol. Here, we demonstrate for the first time that TOBC enhances tissue regeneration by fine-tuning inflammatory responses in both zebrafish and human epithelial cells.
Using the zebrafish caudal fin amputation model at 72 hours post-fertilization (hpf), larvae were treated with TOBC (1 or 2 mg/mL). In Tg(mpx:GFP) transgenic fish, 1 mg/mL TOBC promoted early neutrophil recruitment at 6 hours post amputation (hpa) and significantly upregulated il1β and irf8, while the higher dose showed no effect. Western blotting revealed early activation of cleaved Il1β at 2 hpa, suggesting inflammasome involvement. At 24 hpa, TOBC increased macrophage infiltration and tnfα expression, followed by enhanced proliferation at 48 hpa, as shown by elevated Pcna and Tgfβ1 protein levels and EdU incorporation. Fin outgrowth was markedly greater in TOBC-treated larvae compared to controls. Notably, co-treatment with the caspase-1 inhibitor AC-YVAD-CMK abolished these effects, confirming that TOBC acts through inflammasome-dependent Il1β activation.
Parallel in vitro experiments using human bronchial epithelial BEAS-2B cells confirmed the pro-regenerative role of TOBC. Treatment with 1 mg/mL TOBC increased cell viability and accelerated the cell cycle (S/G2 phases), elevated IL-1β and EGF secretion, and induced cytoskeletal remodeling through vimentin disassembly. Moreover, TOBC-treated cells displayed faster wound closure in scratch assays, demonstrating enhanced proliferative and migratory capacities.
Collectively, these results indicate that TOBC establishes a regeneration-permissive microenvironment by coordinating inflammatory and proliferative cues. By triggering a transient, well-orchestrated inflammatory phase through Il1β and Tnfα modulation, followed by Tgfβ1 and EGF-driven proliferation, TOBC supports effective tissue repair. Given its safety as a dietary supplement and its efficacy in both in vivo and in vitro systems, TOBC represents a promising candidate for therapeutic applications in wound healing and regenerative medicine.
Acknowledgements: This project was funded by the European Union – Next Generation EU. Codice Progetto: ECS00000041; CUP Progetto: C43C22000380007; Titolo Progetto: Innovation, digitalization and sustainability for the diffused economy in Central Italy – VITALITY
Verità, ricostruzione del fatto e controllo giurisdizionale nel procedimento di estradizione passiva
Il giudice tributario dopo le riforme
si valuta se gli auspici di Francesco Moschetti, a proposito della parità delle armi nel processo tributario, possano dirsi realizzati dopo la stagione di riforme 2022/2
Sanità e Amministrazione: verso un "nuovo" equilibrio tra pubblico e privato nel prisma del risultato
Dietary supplementation with Bacillus velezensis and Pichia guilliermondii improves growth performance through intestinal morphology and functionality enhancement in weaning piglets
The post-weaning period in piglets is often associated with significant changes in intestinal structure and function, which can negatively affect growth and performance. This study aimed to evaluate the effects of dietary supplementations with prebiotics and/or probiotics on intestinal morphology and functionality during the post-weaning phase. Piglets were supplemented with different diets, including combinations of Pichia guilliermondii (prebiotic, PRE) and Bacillus velezensis (probiotic, PRO), and their growth performance, intestinal histology, and functionality were assessed. Growth performance was evaluated in the post-weaning period, with a notable improvement in weight gain observed in piglets receiving the combined prebiotic/probiotic supplementation. Morphometric analysis revealed significant differences in intestinal morphology, particularly in the small intestine. The PRE/PRO combination was most effective in improving villus size in the duodenum and ileum at early post-weaning stages, while the jejunum showed a greater sensitivity to weaning stress. Molecular analysis indicated diet-dependent changes in the expression of key markers involved in nutrient absorption and mucosal integrity, including SLC15A1 and TJP1. Additionally, 16S rRNA sequencing revealed diet-related changes in gut microbiota composition where α-diversity and β-diversity increased independently of the diets and, specific beneficial taxa (e.g., Lachnospiraceae) were enriched in the supplemented groups. These microbial shifts were consistent with the improved mucosal thickness observed in the colon, suggesting a potential contribution of microbial modulation to epithelial integrity of the large intestine. Overall, the results suggest that the synbiotic supplementation of prebiotics and probiotics can enhance intestinal integrity in both the small and large intestine, promote growth, and improve overall gut health in post-weaning piglets
Microplastic contamination: a human health concern and an analytical challenge
The pollution caused by plastics, for which demand worldwide is increasing every year, is not only a problem for the environment but also poses risks to food safety and human health. Microplastics (MPs) are polymeric particles with dimensions between 5 mm and 0.1 μm that are generated from degraded plastic as it is subjected to mechanical and atmospheric phenomena. Further degradation leads to the formation of even smaller particles, nanoplastics (NPs), with sizes down to 1 nm.
Studies report harmful effects of these anthropogenic particles on marine and terrestrial ecosystems; they can affect soil performance, interfere with photosynthesis, and have toxic effects on animals, undermining survival mechanisms such as reproduction and foraging. Some effects of MPs on human health have been reported; however, their toxicity is still not well-documented. In addition, their negative activity can be linked to their ability to act as a vehicle for pathogens and other known contaminants, thus increasing human exposure to these substances.
One of the main routes of human contact with MPs and NPs is by ingestion, therefore, through the food and beverages we consume, which are eventually contaminated. Raman microspectroscopy is one of the most popular analytical techniques, included by the European Union among those to measure MPs in water intended for human consumption. MPs have been reported in various foods and drinks. Among complex matrices, seafood is the most studied due to its connection with the marine environment.
The scientific community’s interest in the presence of MPs and NPs in food is steadily increasing, with several food products considered to be growing. Nevertheless, there is still a need for reliable and comparable data and the development of standardized procedures for a greater variety of foods to fill the methodological gaps in this scientific field and enable a proper risk assessment evaluation