This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.

This mini review describes the role of gut and lung microbiota during respiratory viral infection and discusses the implication of the microbiota composition on the immune responses generated by the vaccines designed to protect against these pathogens. This is a growing field and recent evidence supports that the composition and function of the microbiota can modulate the immune response of vaccination against respiratory viruses such as influenza and SARS-CoV-2. Recent studies have highlighted that molecules derived from the microbiome can have systemic effects, acting in distant organs. These molecules are recognized by the immune cells from the host and can trigger or modulate different responses, interfering with vaccination protection. Modulating the microbiota composition has been suggested as an approach to achieving more efficient protective immune responses. Studies in humans have reported associations between a better vaccine response and specific bacterial taxa. These associations vary among different vaccine strategies and are likely to be context-dependent. The use of prebiotics and probiotics in conjunction with vaccination demonstrated that bacterial components could act as adjuvants. Future microbiota-based interventions may potentially improve and optimize the responses of respiratory virus vaccines.

MTORopathies represent a group of neurodevelopmental disorders linked to dysregulated mTOR signaling, resulting in conditions such as tuberous sclerosis complex, focal cortical dysplasia, hemimegalencephaly, and Smith–Kingsmore Syndrome. These disorders often manifest with epilepsy, cognitive impairments, and, in some cases, structural brain anomalies. The mTOR pathway, a central regulator of cell growth and metabolism, plays a crucial role in brain development, where its hyperactivation leads to abnormal neuroplasticity, tumor formation, and heightened neuronal excitability. Current treatments primarily rely on mTOR inhibitors, such as rapamycin, which reduce seizure frequency and tumor size but fail to address underlying genetic causes. Advances in gene editing, particularly via CRISPR/Cas9, offer promising avenues for precision therapies targeting the genetic mutations driving mTORopathies. New delivery systems, including viral and non-viral vectors, aim to enhance the specificity and efficacy of these therapies, potentially transforming the management of these disorders. While gene editing holds curative potential, challenges remain concerning delivery, long-term safety, and ethical considerations. Continued research into mTOR mechanisms and innovative gene therapies may pave the way for transformative, personalized treatments for patients affected by these complex neurodevelopmental conditions.

To investigate the prevalence and factors associated with no intention to exclusively breastfeed for the first 6 months of life in a sample of women in the first 24 h postpartum during the hospital stay. Cross-sectional study with data from screening phase of a birth cohort. The proportion of mothers who did not intend to breastfeed exclusively for 6 months (primary outcome) derived from a negative response to the question "Would you be willing to try to breastfeed exclusively for the first 6 months?", in an interview conducted by previously trained interviewers. Crude and adjusted prevalence ratios (PR) with 95% confidence intervals were obtained by Poisson regression with robust variance. A total of 2964 postpartum women were interviewed. The overall prevalence of mothers who did not intend to breastfeed exclusively for 6 months was 17.8% (16.4-19.1%). After adjusting for maternal age and type of pregnancy (singleton or multiple), no intention to exclusively breastfeed was higher in mothers with a monthly household income < 3 minimum wages (PR, 1.64; 1.35-1.98) and in those who intended to smoke 4-7 days/week after delivery (PR, 1.42; 1.11-1.83). The presence of significant newborn morbidity (PR, 0.32; 0.19-0.54) and intention to breastfeed up to 12 months (PR, 0.46; 0.38-0.55) had a protective effect against not intending to breastfeed exclusively for 6 months. Approximately 1 in every 5 mothers did not intend to breastfeed exclusively for 6 months. Strategies aimed at promoting exclusive breastfeeding should focus attention on mothers from lower economic strata and smokers.

Immunosuppressive drugs remain essential for preventing rejection but carry significant toxicities, underscoring the need for safer, physiology-based immunomodulators. Tributyrin, a prodrug of butyrate with improved systemic bioavailability, has emerged as a metabolically driven immune regulator. Here, we evaluated whether oral tributyrin promotes immune tolerance and improves graft outcomes in preclinical transplantation models. In minor-mismatch skin transplantation, tributyrin-treated recipients exhibited a significant, Treg-dependent prolongation of graft median survival time (33 [IQR 24.0-40.5] vs. 15.5 [IQR 12.0-18.0] days; p=0.0007). In a semi-allogeneic heart model, tributyrin similarly extended graft survival (52 [IQR 27.0-67.5] vs. 14.5 [IQR 12.25-22.0] days; p=0.0038). Oral tributyrin increased the frequency and activation of graft-infiltrating Tregs, marked by elevated IL-10, CTLA-4, LAG-3, and CD25, while reducing CD8⁺ T-cell infiltration and their IFN-γ and granzyme B production. Tributyrin treatment also modulated the intragraft innate compartment, reducing proinflammatory M1-macrophage signatures while promoting M2-macrophages with increased IL-10 expression. Systemically, splenocytes from treated recipients produced more IL-10 and displayed selective hyporesponsiveness to donor, but not to third-party antigens, consistent with antigen-specific regulation. Collectively, these findings demonstrate that oral tributyrin enhances regulatory pathways, suppresses alloreactive effector responses, and prolongs allograft survival, supporting its potential as a safe metabolic adjunct in transplantation.

This review explores the transformative role of induced pluripotent stem cells (iPSCs) and organoids in advancing neuropathology research. Focused on Alzheimer's disease, epilepsy, Parkinson's disease, and spinal cord injury, iPSCs offer patient-specific disease modeling with regenerative therapy potential. The versatility of iPSCs, their ability to differentiate into the main neuronal cell types, and their integration into three-dimensional organoid models enable the recreation of complex tissues in vitro. Improvement of organoid and iPSCs generation protocols and the selection of appropriate donor cell types are highlighted as crucial steps toward the application of these new technologies to overcome tumorigenic potential and other challenges. iPSCs demonstrate promise in regenerative therapies, as evidenced by successful applications in animal models.