Alba Río-Ropero, Álvaro González-Camuesco, Anna I Mackey, Inês Caldeira, Mathieu Lepas, Edith Lucas-Vadillo, Cristina Cunha, Agostinho Carvalho, Matthew Z Anderson, Jorge Amich
T. wilfordii may exert anti-CRC effects through a multi-component, multi-target, and multi-pathway mechanism. Tryptophenolide (Lei4) showed moderate but reproducible anti-CRC activity and directly inhibited EGFR kinase activity in vitro, supporting EGFR pathway inhibition as one mechanism contributing to its cellular effects. These findings provide a basis for further optimization and mechanistic evaluation of T. wilfordii -derived active compounds in CRC.
Persulfidation is a post-translational modification involving the specific conversion of thiols (-SH) to persulfide groups (-SSH) on cysteine residues in target proteins. This modification plays critical roles in numerous physiological and cellular processes. Previously, we demonstrated that host cell persulfidation levels influence the effectiveness of antifungal immunity against the fungal pathogen Aspergillus fumigatus. In this study, we sought to further elucidate the relationship between persulfidation and the immune response. To this end, we defined the persulfidated proteins (the persulfidome) in alveolar epithelial cells that were challenged with A. fumigatus and/or exposed to a sulfide donor, which increases cellular persulfidation. Our findings suggest that persulfidation indirectly modulates immunity through changes in RNA metabolism and translation. Additionally, calprotectin was persulfidated in response to A. fumigatus exposure, and this modification is essential for maintaining its immune-related function under oxidative stress. Our results suggest that persulfidation positively influences generalized and specific immune responses.