Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D₃ improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D₃ may modulate these microRNAs to improve asthma symptoms.

The γδ T cells belong to a subgroup of T cells known as non-conventional T cells due to their limited T cell receptor (TCR) repertoire and ability to recognize non-peptide antigens. They play a crucial role in combating infections and tumors. Vγ9Vδ2 T cells are typically activated by molecules containing diphosphate groups, collectively known as phosphoantigens (pAgs), through a non-canonical mechanism which involves the intracellular domain of butyrofilin (BTN)3A1 protein. However, no FDA-approved drugs have yet been shown to activate them, and the underlying cellular mechanisms remain unknown. In this study, we combined high-throughput virtual screening of an FDA-approved drug database with in vitro cellular assays to identify potential γδ T cells activators. Our findings demonstrate that Nitazoxanide (NTZ) and Tinidazole induce moderate elicited a statistically significant increase in interferon (IFN)-γ production of Vγ9Vδ2 T cells by their probably interaction with the pAg binding site of BTN3A1. Additionally, NTZ induces expression of CD107a, but only at the highest concentrations tested and promotes the upregulation of HLA-DR in total PBMCs and CD14⁺ monocytes. Blocking BTN3A with a specific antibody led to a marked reduction in all NTZ-induced activations. This work identifies NTZ as a previously unrecognized activator of γδ T cells, highlighting its immunomodulatory potential beyond its known clinical uses. These findings broaden our understanding of γδ T cells pharmacology and suggest new opportunities for drug repurposing and the design of novel chemical scaffolds. Further mechanistic studies will be essential to fully define how NTZ engages the BTN3A–γδ T cells axis.

The VHL–HIF-1α–VEGF axis regulates angiogenesis and metabolism. Beyond oncology, pVHL is essential for pancreatic β-cell function and is reduced in hypercaloric diet (HCD)-induced type 2 diabetes mellitus (T2DM). This study aimed to overexpress pVHL in pancreatic tissue and evaluate its effects on blood glucose levels and the expression of proteins related to glucose metabolism in the pancreas. HCD-induced diabetic C57BL/6 and BALB/c mice received a single intrapancreatic injection of an adenoviral vector (1 × 10¹² viral particles) encoding the murine Vhlh gene (AdVHL) to induce transient pVHL overexpression. The glycemic delta (post-load glucose minus fasting) and net incremental area under the curve (niAUC) were determined on days 3, 6, 9, 12, and 15 post-treatment, as the peak in GFP overexpression (used as a surrogate reporter of transduction efficiency) was detected between days 9 and 12. Immunohistochemistry (IHC) and immunofluorescence (IF) were used to assess the expression of pVHL, HIF-1α, GLUT-1, GLUT-2, and insulin in pancreatic tissue. AdVHL treatment significantly decreased the glycemic delta and niAUC in mice with T2DM (p < 0.01). On day 15 after treatment, HIF-1α and GLUT-1 expression were markedly reduced in AdVHL-treated mice (p < 0.01), while GLUT-2 and insulin were significantly increased (p < 0.01). These results were reproduced in both mouse strains. Transient overexpression of pVHL in pancreatic tissue of mice with T2DM was associated with decreased glucose levels and changes in the expression of proteins related to glucose metabolism in the pancreas, resembling a healthier phenotype than that of mice with T2DM. These findings support an important functional role of the pVHL–HIF-1α axis in pancreatic physiology, provide a proof-of-concept for further mechanistic and translational studies, and implicate pVHL in the altered glucose metabolism observed in T2DM.