Monielle Sant’ana

Chronic, non-resolving inflammation is a major contributor to impaired wound healing in diabetes. Annexin A1 (AnxA1), a pro-resolving mediator, and its mimetic peptide Ac_2–26 have demonstrated therapeutic potential in modulating inflammatory responses. In this study, we evaluated the effects of topical Ac_2–26 hydrogel in a streptozotocin-induced diabetic wound model. Treatment significantly accelerated wound closure, improved tissue architecture, and reduced leukocyte infiltration. Immunohistochemical analysis revealed diminished mast cell accumulation and IL-1β expression in treated wounds. Complementary transcriptomic profiling supported the downregulation of pro-inflammatory genes, including Il1b and mast cell-related mediators, confirming the peptide’s regulatory effect on the wound immune landscape. Mounting evidence suggests that dysregulated mast cell activity plays a role in the heightened inflammatory tone and delayed tissue repair observed in diabetic wounds. In our model, Ac_2–26 hydrogel treatment attenuated IL-1β expression, suggesting an indirect downregulation of NLRP3 inflammasome activation, potentially mediated through mast cell modulation, though effects on other cell types within the wound microenvironment cannot be excluded. While definitive causality cannot be assigned, the integration of histological and transcriptomic data highlights mast cells as contributors to the IL-1β-driven inflammatory burden in diabetic wounds. These findings underscore the immunomodulatory capacity of Ac_2–26 and its potential to restore resolution pathways in chronic wound settings, positioning it as a promising candidate for future therapeutic development.

Background/Objectives: The annexin A1 (AnxA1) protein has proven important in ocular disease homeostasis and holds great therapeutic promise. However, its role in the context of the healthy retina remains unknown. Therefore, this study used electroretinography (ERG) to investigate the role of endogenous AnxA1 in the retinal function of wild-type (WT) and AnxA1 knockout mice (AnxA1^−/−). Methods: An extensive repertoire of full-field ERG was applied to AnxA1^−/− and WT mice to examine retinal physiology. Morphometric analyses of the retina were conducted. Results: Our results revealed significant differences in the implicit time of a-wave and b-wave between the WT and AnxA1^−/− groups under scotopic conditions. The negative and positive amplitude components of mesopic ON responses were higher in the AnxA1^-/- group than in the WT group. In contrast, the implicit time of mesopic ON responses were significantly higher in the WT group than in the AnxA1^-/- WT group. However, in photopic OFF responses, only the implicit time was significantly longer in the WT group than in the AnxA1^−/− group. In the histomorphometric analysis, the retina of AnxA1^−/− mice shows increased thickness. Conclusions: The absence of AnxA1 alters retinal morphology and physiology.

Background: Garcinia brasiliensis is traditionally known for its medicinal properties. Objectives: Here, we investigated the effects of crude extract (CE) and ethyl acetate fraction (EAF) obtained from G. brasiliensis leaves on the ascitic (EA) and solid (ES) forms of Ehrlich tumors. Methods: Induced and uninduced BALB/c mice were treated intramuscularly, for 7 or 14 days, with saline solution or CE and EAF, both at a 10% concentration, based on in vitro cytotoxicity assessment. Biochemical analyses were also performed to evaluate in vivo cytotoxicity. In relation to tumor-induced animals, morphological changes, plasma enzymes, inflammatory mediators and the induction of apoptosis were analyzed, in addition to histopathological studies, to evaluate the inhibition of tumor growth. Results: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT) were regulated by CE and EAF administration. Furthermore, both treatments were effective in inhibiting tumor growth in EA and ES by modulating the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α, decreasing mast cells numbers and inducing apoptosis. Conclusions: This research indicates that both CE and EAF from G. brasiliensis leaves have potential antitumor effects with low cytotoxicity.