Biology subjects

Castro, C. A.

Publications and source records attributed to Castro, C. A..

3 recordsLinked to original sources

bioRxiv2024

Tumoral hypoxic extracellular vesicles create a protective microenvironment for triple-negative breast cancer

The highly metastatic triple-negative breast cancer (TNBC) relies on the tumor microenvironment (TME) to maintain phenotypic heterogeneity and progression. Extracellular vesicles from hypoxic TNBC (EVh) have been previously shown to facilitate tumoral invasion; however, their function in the tumor microenvironment remains unclear. We used a novel method to investigate the TME in vitro called multicellular circulating co-culture, to characterize how EVh interferes with tumoral and endothelial cells, fibroblasts, monocytes and macrophages. EVh promoted monocyte differentiation to M2-like macrophages and inhibited macrophage-derived phagocytosis in endothelial and tumoral cells. The protection of endothelial, tumoral and stromal cellular integrity by EVh increased pro-tumoral and pro-angiogenic signaling, collagen matrix synthesis and showed a potential differentiation to cancer-associated fibroblasts. Our findings highlight the critical role of EVh in protecting tumor cells, indicating its cooperation towards a protective TME, which was demonstrated by the multicellular circulating co-culture and conventional co-culture protocols. These findings lead to an adequate system with potential for investigating other tumor-related processes, including circulating tumor cells and metastasis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/621519v3_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@4ff8a0org.highwire.dtl.DTLVardef@4bf15corg.highwire.dtl.DTLVardef@1d2f105org.highwire.dtl.DTLVardef@1cd8346_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

The microbiota extends the reproductive lifespan by safeguarding the ovarian reserve

Infertility is a devastating condition affecting one in six people globally. In many cases, the underlying causes are unknown. Emerging evidence suggests that the microbiota influences reproduction, yet the mechanistic link between the microbiota, ovarian function, and length of the fertile lifespan remain unexplored. Here we report that the microbiota controls the length of the reproductive lifespan by maintaining the primordial follicle pool, a process mediated by microbiota-derived short chain fatty acids modulating gene regulatory networks crucial for the survival of the ovarian reserve. Dietary perturbation of the microbiota during a critical developmental window is sufficient to diminish the ovarian reserve, reduce oocyte retrieval, and impair preimplantation embryo viability, mirroring challenges in human fertility treatments. Targeted interventions to restore microbiota improve assisted reproductive outcomes, particularly when implemented early. These findings reveal a novel contribution of host-microbe interactions in mammalian reproduction and demonstrate that the microbiota impacts ovarian function and fertility.

developmental biology↗

bioRxiv2023

Permethylation as a Strategy for High Molecular Weight Polysaccharide Structure Analysis by NMR& Case Study of Xylella fastidiosa EPS

Current practices for structure analysis of extremely large molecular weight polysaccharides via solution-state NMR spectroscopy incorporate partial depolymerization protocols that enable polysaccharide solubilization in suitable solvents. Non-specific depolymerization techniques utilized for glycosidic bond cleavage, such as chemical degradation or ultrasonication, potentially generate structure fragments that can complicate the complete characterization of polysaccharide structures. Utilization of appropriate enzymes for polysaccharide degradation, on the other hand, requires prior structure information and optimal enzyme activity conditions that are not available to the analyst working with novel or unknown compounds. Herein, we describe the application of a permethylation strategy that allows the complete dissolution of the intact polysaccharides for NMR structure characterization. This approach is utilized for NMR analysis of Xylella fastidiosa EPS, which is essential for the virulence the plant pathogen that affects multiple commercial crops and is responsible for multibillion dollar losses each year.

biochemistry↗