Ricardo Key Yamazaki

The Research Topic Omega-3 Fatty Acids and Immunometabolism in Health and Disease integrates evidence from population studies, clinical observations, and experimental models to examine how omega-3 fatty acids contribute to immunometabolic regulation. Rather than focusing on isolated outcomes, the included articles collectively advance understanding of shared immunometabolic mechanisms and critical windows during which omega-3 availability appears particularly influential. Across diverse models, studies converge on the idea that omega-3 fatty acids support metabolic flexibility and immune balance in ways that depend heavily on timing, dietary context, and interactions among fatty acids.At the population level, long-term epidemiological analysis demonstrates that inadequate omega-3 intake continues to contribute meaningfully to cardiometabolic disease burden, even in settings where age-standardized mortality has declined. This relationship is illustrated by recent work quantifying the ischemic heart disease burden attributable to insu icient omega-3 intake across multiple decades and demographic strata [LINK: Luo et al., 2025]. These findings reinforce the public health relevance of omega-3 consumption and underscore the importance of dietary strategies that account for demographic shifts such as population aging. Importantly, they also provide a necessary backdrop for interpreting mechanistic and interventional studies, linking cellular and tissue-level e ects of omega-3 fatty acids to outcomes observed at the population scale.Clinical relevance is further supported by emerging evidence that omega-3 fatty acids may contribute to immune recovery following severe inflammatory challenges. In pediatric populations recovering from multisystem inflammatory syndrome associated with SARS-CoV-2 infection, supplementation with docosahexaenoic acid has been associated with improvements in circulating omega-3 status and favorable trends in inflammatory markers [LINK: Verduci et al., 2025]. Although exploratory, these observations suggest that omega-3 fatty acids may contribute to immune resolution during convalescence and highlight the potential for targeted nutritional approaches to complement existing clinical care.A significant contribution of this Research Topic lies in its emphasis on early life as a sensitive period for immunometabolic programming. Experimental studies demonstrate that maternal omega-3 exposure during gestation and lactation can influence o spring metabolic trajectories, inflammatory signaling, and oxidative balance. In models of postnatal overfeeding, maternal fish oil supplementation attenuated metabolic and inflammatory disturbances in adult o spring [LINK: Perígolo Lopes et al., 2025], while complementary work using maternal supplementation with a plant-based omega-3 source showed protection against metabolic impairments induced by postnatal undernutrition [LINK: Leão et al., 2025]. Considered together, these studies indicate that omega-3 fatty acids contribute to metabolic resilience by shaping developmental trajectories, regardless of whether the early-life nutritional challenge involves excess or restriction.Beyond absolute omega-3 intake, the studies in this Topic also advance understanding of the importance of dietary fatty acid balance and metabolic context. Experimental manipulation of the omega-6 to omega-3 ratio has demonstrated pronounced e ects on lipid handling, endocrine signaling, and tissue-specific metabolic pathways. Evidence from controlled animal nutrition models indicates that reducing the dominance of omega-6 fatty acids improves growth e iciency, lipid profiles, and regulation of metabolic hormones. It modulates gene expression in the liver, intestine, and skeletal muscle [LINK: Guo et al., 2025]. Complementary mechanistic work further supports the role of omega-3 fatty acids in coordinating metabolic and inflammatory pathways across tissues, reinforcing the concept that omega-3 e ects on immunometabolism extend beyond single organs or outcomes [LINK: Liang et al., 2025].Taken together, the contributions in this Research Topic reinforce several key principles relevant to immunometabolism. Omega-3 fatty acids act across tissues and physiological systems to support coordinated metabolic and immune responses. Their e ects are shaped not only by dose but also by the timing of exposure, interactions with other dietary fats, and the organism's metabolic state. Early developmental periods and recovery from inflammatory stress appear exceptionally responsive to omega-3 availability, suggesting that nutritional strategies should be context-specific rather than uniform across populations. these advances, significant gaps remain. The molecular pathways linking omega-3 fatty acids to immune resolution and metabolic adaptation require further clarification, particularly in human studies. The roles of specialized pro-resolving lipid mediators, tissue-specific signaling networks, and interactions with physical activity and the gut microbiome remain incompletely defined. In addition, future research must more e ectively address sex-specific responses, interindividual variability, and the long-term sustainability of omega-3-rich dietary patterns in diverse populations. By integrating evidence across epidemiology, clinical research, developmental biology, and experimental nutrition, this Research Topic provides a cohesive view of omega-3 fatty acids as central regulators of immunometabolic health. Rather than presenting isolated findings, the collection emphasizes convergent mechanisms and translational relevance, thereby positioning omega-3 fatty acids within a broader framework of metabolic and immune regulation. Continued interdisciplinary research will be essential to translate these insights into practical strategies for disease prevention and health promotion across the lifespan.

Achyrocline satureioides (Lam.) DC. is a medicinal plant traditionally used in Brazilian ethnomedicine through infusion and decoction for various therapeutic purposes. The objectives were to determine the antimicrobial activity of the A. satureioides extract against Pseudomonas aeruginosa and to describe a novel technique using iron dextran solution to enhance the activity of bioactive compounds and antimicrobial agents. The extract was characterized for phytochemical composition, antioxidant activity in vitro, and antimicrobial activity. The extract exhibited a high content of phenolic compounds and considerable antioxidant activity. Concerning the antimicrobial activity, it inhibited the development of the strain at low concentrations, with a minimum inhibitory concentration (MIC) of 0.0390 mg/ml for the pure extract and 0.0195 mg/ml for the extract diluted in iron dextran, thus presenting bacteriostatic activity at these concentrations. It showed a bactericidal activity from 10 mg/ml, with inhibition halo of 2.11±0.19 and 2.22±0.50 mm for the pure extract and 2.55±0.19 and 2.66±0.33 mm for the extract diluted in iron dextran in the disk diffusion and punch hole methods, respectively. A. satureioides has an important antimicrobial activity, and the iron dextran solution enhanced the effect of bioactive compounds and antimicrobial agents.

By-products generated in the winemaking industry contain compounds with health-promoting properties, which can be reintroduced into the food production chain. This study evaluated the use of a by-product from the industrial processing of grapes as an ingredient in the manufacture of Petit Suisse cheese, made with A2A2 milk and the addition of the probiotic Bifidobacterium animalis subsp. lactis HN019. Two Petit Suisse formulations were made in three independent batches: a control formulation without the addition of the by-product (F0) and a formulation containing 10% of the by-product (F1). The proximate composition of the cheeses was characterized on the first day after manufacturing them. The addition of the by-product led to an increase in ash, lipids, and carbohydrates and a reduction in moisture and protein contents. The physicochemical characterization and the texture profile analysis showed no changes throughout the product’s shelf life. The probiotic counts remained abundant (~eight log CFU/g) in both formulations with no changes seen throughout the shelf life period. Scanning electron microscopy images showed the added bacteria had typical structures. No differences were observed in the fatty acid profiles of the formulations, and both exhibited a total of 18 fatty acids, including saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs). Additionally, the by-product conferred antioxidant activity to the F1 formulation. The addition of the by-product in fresh cheese may be an interesting approach in regards to the processing technology used, its microbiological safety, and its nutritional value. The use of A2A2 milk and a probiotic culture thus enhanced the Petit Suisse cheese, resulting in a healthier product.

Achyrocline satureioides, a medicinal plant widely used in Brazilian traditional medicine for diverse healing applications, has been underexplored for its potential anticancer properties. This study aimed to investigate the antitumor potential of A. satureioides extract on SK-Mel-28 melanoma cells, using an innovative approach devised by the authors that involves a potentiating solution of iron dextran to enhance the efficacy of bioactive and anticancer agents. The extract was characterized for its phytochemical composition, antioxidant effect, and anticancer activity. The anticancer activity was assessed for various concentrations of the extract, both with and without the iron dextran potentiating solution. The analysis revealed a high concentration of total phenolics and flavonoids in the extract, along with moderate antioxidant activity. Notably, the extract exhibited substantial anticancer activity, markedly reducing cell proliferation and influencing several cancer-related markers, especially at a concentration of 500 μg in combination with the potentiating solution. Importantly, the treatment exhibited no toxicity to healthy cells, showing selective cytotoxicity and robust anticancer potential of A. satureioides, particularly when combined with the iron dextran solution. This study represents the inaugural report of the potentiating effect of A. satureioides as a promising candidate for further cancer treatment research.

Campomanesia xanthocarpa Berg. (Myrtaceae), also known as “guabiroba”, is widely distributed in the South and Southern regions of Brazil and has been used by local families as folk medicine to treat several diseases. This study aimed to evaluate the bioactive compounds of guabiroba fruits and leaves, such as flavonoids, carotenoids, chlorophyll, total phenolics, tannins, and coumarins. The biological effect of different parts of C. xanthocarpa (leaf and pulp) was also investigated for the immunomodulatory activity on RAW 264.7 macrophages, and anti-cancer effects on H295R adrenocortical cells under different concentrations and extraction protocols. Extracts from guabiroba leaves and pulp using 70% ethanol and n-hexane as a solvent by magnetic stirring, as well as ethanolic extracts from leaves and pulp obtained by heat reflux extraction were produced. Most of the bioactive compounds were found in the leaves rather than the fruit pulp. The in vitro assays showed that the leaf extraction with hexane affected the viability assay in the adrenocortical cell line H295R, while the pulp extracted with hexane activated the macrophage cell line RAW 264.7. Therefore, C. xanthocarpa leaves and pulp have proven to affect macrophage and adrenocortical cell lines in a dose-dependent manner.