Biology subjects

De la Fuente, J.

Publications and source records attributed to De la Fuente, J..

3 recordsLinked to original sources

bioRxiv2026

Placental lipid handling, growth and inflammatory pathways are modified by a maternal Mediterranean diet

AimsThe Mediterranean diet is associated with reduced cardiometabolic risk, yet its physiological effects during pregnancy and its impact on placental metabolism remain incompletely understood. This study aimed to determine whether maternal adherence to a Mediterranean diet during pregnancy influences placental lipid metabolism and signalling pathways involved in nutrient handling, tissue remodelling, and inflammation, and to assess their relationship with pregnancy outcomes. MethodsPlacental samples and clinical outcome data were analysed from pregnant women participating in an unblinded randomized clinical trial of a Mediterranean diet intervention. Placental lipid composition was quantified and the expression of genes and signalling pathways involved in lipid metabolism, nutrient transport, inflammation, and tissue remodelling was evaluated. ResultsMaternal adherence to a Mediterranean diet during pregnancy was associated with significant alterations in placental lipid composition, including reduced C18:0 and C24:0 and increased C18:1n9c, C20:3n6, and C22:0, with lower total short-chain fatty acids and higher monounsaturated fatty acids. Placental expression of lipid metabolism regulators ALOX15 and PPAR{gamma} was reduced, alongside downregulation of AKT and p38 MAPK signalling pathways. Placentas from mothers adhering to the Mediterranean diet also showed lower expression of amino acid and glucose transporters SLC3A2 and SLC2A1, as well as altered inflammatory and extracellular matrix remodelling markers, including decreased SOCS3 and GHR and increased PAI1 and MMP3. ConclusionsMaternal adherence to a Mediterranean diet during pregnancy modifies placental lipid composition and regulates pathways involved in lipid handling, nutrient transport, inflammation, and tissue remodelling, providing insight into mechanisms linking maternal diet with placental metabolic function.

physiology↗

bioRxiv2022

Identification of transcriptional network disruptions in drug-resistant prostate cancer with TraRe

Metastatic castration-resistant prostate cancer (mCRPC) presents very low survival rates due to lack of response or acquired resistance to the available therapies. To date no molecular mechanisms of resistance have been identified, pointing out their complex dynamics. To identify key genes and processes associated with phenotypically-driven regulatory differences, we developed TraRe, a computational method that provides a three-tier analysis: i) at the network level, inferring differentially regulated modules; ii) at the regulon level, identifying regulatory relationships linked to phenotypic differences; and iii) at the single gene level, identifying TFs consistently linked to rewired modules. We applied TraRe (available in Bioconductor with full documentation) to transcriptomic data from 46 mCRPC patients with Abiraterone-response clinical data and uncovered abrogated immune response regulatory modules that showed strong differential regulation in Abi-resistant patients. These modules were replicated in an independent mCRPC study. Further, we experimentally validated key rewiring predictions and their associated transcription factors. Among them, ELK3, MXD1, and MYB were found to have a differential role in cell survival for Abi-response-specific settings. Moreover, we identified the role of ELK3 in cell migration capacity, which could have direct impact on mCRPC. Collectively, these findings shed light on the underlying regulatory mechanisms driving abiraterone response.

bioinformatics↗

bioRxiv2019

Heterogeneous disease-propagating stem cells in juvenile myelomonocytic leukemia

Juvenile Myelomonocytic Leukemia (JMML) is a poor prognosis childhood leukemia usually caused by germline or somatic RAS-activating mutations. The cellular hierarchy in JMML is poorly characterized, including the identity of leukemia stem cells (LSCs). FACS and single-cell RNA-sequencing reveal marked heterogeneity of JMML hematopoietic stem/progenitor cells (HSPCs), including an aberrant Lin-CD34+CD38-CD90+CD45RA+ population. Single-cell HSPC index-sorting and clonogenic assays show that (1) all somatic mutations can be backtracked to the phenotypic HSC compartment with RAS-activating mutations as a \"first hit\", (2) mutations are acquired with both linear and branching patterns of clonal evolution and (3) mutant HSPCs are present after allogeneic HSC transplant before molecular/clinical evidence of relapse. Stem cell assays reveal inter-patient heterogeneity of JMML-LSCs which are present in, but not confined to, the phenotypic HSC compartment. RNA-sequencing of JMML-LSCs reveals upregulation of stem cell and fetal genes (HLF, MEIS1, CNN3, VNN2, HMGA2) and candidate therapeutic targets/biomarkers (MTOR, SLC2A1, CD96) paving the way for LSC-directed disease monitoring and therapy in this disease.

cancer biology↗