Vitamin D and omega 3 fatty acid (ω-3) co-supplementation potentially improves type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation. This cohort study, preliminary to a randomized control trial (RCT), is aimed at evaluating, in a series of T1D children assuming Mediterranean diet and an intake of cholecalciferol of 1000U/day from T1D onset, if ω-3 co-supplementation preserves the residual endogen insulin secretion (REIS). Therefore, the cohort of 22 “new onsets” of 2017 received ω-3 (eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60 mg/kg/day), and were compared retrospectively vs. the 37 “previous onsets” without ω-3 supplementation. Glicosilated hemoglobin (HbA1c%), the daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/day × 4 + HbA1c%), as surrogates of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the ω-3 supplemented group, dietary intakes were evaluated at T0 and T12. As an outcome, a decreased insulin demand (p < 0.01), particularly as pre-meal boluses (p < 0.01), and IDAA1c (p < 0.01), were found in the ω-3 supplemented group, while HbA1c% was not significantly different. Diet analysis in the ω-3 supplemented group, at T12 vs. T0, highlighted that the intake of arachidonic acid (AA) decreased (p < 0.01). At T0, the AA intake was inversely correlated with HbA1c% (p < 0.05; r;. 0.411). In conclusion, the results suggest that vitamin D plus ω-3 co-supplementation as well as AA reduction in the Mediterranean diet display benefits for T1D children at onset and deserve further investigation.

Conventional therapies for immune-mediated diseases, including autoimmune disorders, transplant reactions, and allergies, have undergone a radical evolution in the last few decades; however, they are still not specific enough to avoid widespread immunosuppression. The idea that vaccine usage could be extended beyond its traditional immunogenic function by encompassing the ability of vaccines to induce antigen-specific tolerance may revolutionize preventive and therapeutic strategies in several clinical fields that deal with immune-mediated disorders. This approach has been supported by improved data relating to the several mechanisms involved in controlling unwanted immune responses and allowing peripheral tolerance. Given these premises, several approaches have been developed to induce peripheral tolerance against the antigens that are involved in the pathological immune response, including allergens, autoantigens, and alloantigens. Technological innovations, such as nucleic acid manipulation and the advent of micro- and nanoparticles, have further supported these novel preventive and therapeutic approaches. This review focuses on the main strategies used in the development of tolerogenic vaccines, including the technological issues used in their design and the role of “inverse adjuvants”. Even though most studies are still limited to the preclinical field, the enthusiasm generated by their results has prompted some initial clinical trials, and they show great promise for the future management of immune-mediated pathological conditions.

Background: Paclitaxel (PTX) is an anti-neoplastic drug that inhibits not only melanoma cell proliferation but also migration and angiogenesis. ICOS-Fc is a recombinant molecule that triggers ICOS ligand (ICOSL) on tumor cells and cells of the tumor microenvironment and inhibits tumor growth, angiogenesis, and metastasis. This study investigated the effects of chitosan nanobubbles loaded with low doses of PTX and surface decorated with ICOS-Fc (ICOS-Fc-NB-PTX) in inhibiting in vitro and in vivo melanoma cell growth and invasiveness. Methods: Preparation and characterization of nanoformulations, as well as in vitro drug release studies, were carried out. Nanoformulations were studied both in vitro and in vivo. In melanoma cells, viability, migration, and invasion assays were analyzed. For the in vivo experiments, C57BL/6 Wild-type (WT) male mice were injected subcutaneously with D4M-3A cells, a murine melanoma cell line engineered to carry the BRAF^V600E mutation. After treatments, in vivo tumor growth, proliferation, and angiogenesis markers were studied. Results: In vitro tests showed the great ability of ICOS-Fc-NB-PTX to inhibit cell viability, migration, and invasion. These results were confirmed in vivo, where the tumors of mice treated with ICOS-Fc-NB-PTX displayed decreased growth accompanied by downregulation of the proliferation marker Ki-67 and reduced development of CD31⁺ blood vessels. Conclusions: In conclusion, the ICOS-Fc-NB-PTX formulation deserves to be further analyzed as a highly effective combination for melanoma, exerting multifaceted anti-tumor activities.