Nicole Simone de Lima Coelho

Background/Objectives: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition often managed exclusively with insulin. However, the search for adjuvant therapies has gained attention, including dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), despite limited evidence in pediatric populations. To evaluate the impact of DPP4i, alone or combined with SGLT2i, on glycemic control (HbA1c), lipid profile (ApoB and ApoA-I), and renal function (eGFR and albuminuria) in children, adolescents, and young adults with T1DM, this study was conducted. Methods: This cohort study analyzed data from 76 patients with T1DM aged under 25, followed for 4 to 20 months. Patients were grouped based on exposure to DPP4i alone, DPP4i + SGLT2i, or no additional therapy. Glycemic, lipid, and renal parameters were assessed at baseline and follow-up. Results: A significant reduction in HbA1c was observed in the overall sample (p < 0.001), regardless of treatment group, suggesting a positive effect of interdisciplinary care. There were no statistically significant differences in HbA1c variation among the groups. ApoB decreased significantly over time (p < 0.001), and ApoA-I levels were initially higher in the DPP4i + SGLT2i group. A significant reduction in albuminuria was identified in the DPP4i-only group compared to controls (p = 0.029), indicating a potential renoprotective effect. No significant changes in eGFR were observed. The use of DPP4i, with or without SGLT2i, was not associated with significant improvements in glycemic or lipid outcomes compared to standard therapy. However, DPP4i monotherapy was associated with a reduction in albuminuria, suggesting a possible benefit for renal protection. Conclusions: These findings highlight the need for larger, randomized studies to confirm the therapeutic role of these agents in young individuals with T1DM.

Although vaccination remains one of the most impactful interventions in contemporary public health, with consistent and widely documented reductions in morbidity and mortality, the traditional empirical development of vaccines—largely based on trial-and-error strategies—still reflects an incomplete understanding of the complexity underlying immune responses. With the emergence of systems immunology, supported by multi-omics technologies, mathematical modeling, and computational tools, vaccinology has progressively incorporated the integration of multiple biological layers, addressing critical mechanistic gaps and mitigating limitations of the classical model, thereby transitioning from an empirical framework toward a predictive and integrative paradigm. In this context, the present review critically examines how systems immunology contributes to rational vaccine design by exploring its technological foundations—particularly omics approaches—discussing strategies for data integration, analyzing translational implications, and incorporating considerations related to Artificial Intelligence (AI), regulatory governance, ethics, and global equity. Within this evolving landscape, systems vaccinology has demonstrated promising results and optimistic perspectives, particularly regarding predictive capacity, immunological stratification, vaccine personalization, and potential epidemiological impact. At the same time, challenges including reproducibility concerns, risk of overfitting, the distinction between multi-omic correlation and functional causality, the need for longitudinal and experimental validation, algorithmic bias, excessive reliance on computational models, and regulatory barriers to the approval of data-driven vaccines represent important limitations of this approach. Taken together, these considerations indicate that systems immunology constitutes not merely a technological refinement but a genuine paradigm shift, redefining vaccine development as a predictive, iterative, and integrative process that must be scientifically validated and ethically contextualized, with profound implications for global public health.

Liver cancer remains a significant global health challenge, with hepatocellular carcinoma (HCC) being the most prevalent form. Despite advancements in treatment, high recurrence rates and the limited efficacy of conventional therapies highlight the need for novel interventions. Cinobufagin (CB), a bufadienolide extracted from the parotid secretion of Bufo gargarizans and B. melanostictus, has emerged as a promising compound with multiple antitumor mechanisms. This comprehensive review assesses the current evidence regarding CB and its containing medicine, cinobufacini, in liver cancer models. Cinobufacini is a traditional Chinese medicine extract, whereas CB refers specifically to one of its active components. The pharmacodynamic actions of CB include induction of apoptosis, DNA damage, inhibition of proliferation and migration, and modulation of key oncogenic pathways such as PI3K/Akt/mTOR, Akt/ERK, and AURKA-mTOR-eIF4E. Additionally, CB disrupts tumor metabolism and induces oxidative stress. Preclinical studies, both in vitro and in vivo, demonstrate significant antitumor efficacy. However, concerns remain regarding CB’s toxicity profile at high doses. This review emphasizes the therapeutic potential of CB in HCC treatment and advocates for further translational research to optimize its clinical applicability, dosage, and safety.