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Oliveira, S. M.

Publications and source records attributed to Oliveira, S. M..

2 recordsLinked to original sources

3D bioprinting of low-viscosity phase-separated food-grade bioinks by in situ self-assembly

There is a notable gap in the scientific understanding of the cellular role in cultured cell-based foods. Unravelling the effects of the interactions between ingredient micro/nanostructure and cells and their significance on nutrition and texture is of great importance. In addition, bioprinting methods face notable limitations in animal-free formulations and scale. Herein, we introduce a proof-of-concept bioprinting method based on the in situ integration of self-assembling events, allowing printing without supporting baths. Our approach enabled a food-grade 3D bioprinted model with 8.5 mm height and a hardness of 284 mN, supporting the early differentiation of myoblasts producing embryonic myosin heavy chain, after 7 days of differentiation. Cellular protein content increased up to 18-fold per initial cell without changes in construct texture. The method provides a novel concept to produce robust, cell-dense platforms for further research on food-grade bioprinted foods.

bioengineering↗

Unveiling the Mechanisms to Bypass KRAS Inhibition: In Vitro Insights into the Influence of Fibroblast-Secretome

Novel KRAS-targeted therapies unlocked new treatment options for previously untreatable patients. However, in colorectal cancer (CRC), resistance to KRAS-targeted therapy develops rapidly, making it imperative to understand its underlying mechanisms. Cancer-associated fibroblasts (CAFs) induce therapy resistance by generating and maintaining cancer stem cells (CSCs). Additionally, CAFs secretome can modulate KRAS mutant CRC cells proteomic profile, independently of mutant KRAS. Hence, we investigated whether CAF-derived factors could induce resistance to KRAS inhibition by promoting a KRAS-independent stem-like phenotype. Evaluation of KRAS-mutant CRC cell lines (HCT15, HCT116, and SW480) revealed unique basal stem cell marker expression levels. Silencing KRAS lead to up-regulation of CD24, down- regulation of CD49f and CD104, and reduced stemness. However, CAF-secreted factors attenuated these effects, restoring stem cell markers expression and increasing stemness. RNA sequencing showed that CAF-secreted factors upregulate pro-tumorigenic pathways in KRAS-silenced cells, including cell cycle control, epithelial-mesenchymal transition (EMT), NOTCH, and immune regulation, leading to increased cell cycling and exit from quiescence. Overall, we provide mechanistic insights illuminating the role of fibroblasts in counteracting KRAS silencing-induced growth inhibition and enhancing stemness. Our results show that the limited success of KRAS-targeted therapies is not only derived from cell-intrinsic factors but also dependent on external factors derived from the tumor microenvironment, thus opening avenues to improve therapy responses in CRC.

cancer biology↗