Biology subjects

Perpina-Clerigues, C.

Publications and source records attributed to Perpina-Clerigues, C..

4 recordsLinked to original sources

bioRxiv2023

Emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

NOD-like receptors are innate immunity sensors that provide an early and effective response to pathogenic or injury conditions. However, abnormalities in these receptors may cause excessive inflammation. Our studies have reported that an activation of the NLRP3-inflammasome complex in ethanol-treated astrocytes and in chronic alcohol-fed mice could be associated with neuroinflammation and brain damage. Considering the therapeutic role of the molecules contained in the extracellular vesicles (EVs) derived by mesenchymal stem cells (MSC-EVs), the present study aims to evaluate whether the intravenous administration of MSC-EVs from adipose tissue, through inhibiting the NLRP3 inflammasome activation, is capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking. We demonstrate that MSC-EVs ameliorate the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes (e.g., NLRP1, NLRC4 and AIM2), as well as the alterations of inflammatory genes (IL-1{beta}, IL-18, iNOS, NF-{kappa}B, MCP-1 and CX3CL1) and miRNAs (miR-21a-5p, miR-146a-5p and miR-141-5p) induced by binge-like ethanol treatment in adolescent mice. Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways. Taken together, these findings provide, for the first time, evidence of the therapeutic potential of MSC-derived EVs to restore the hippocampal neuroinflammatory response through the NLRP3 inflammasome activation induced by binge drinking in adolescence.

neuroscience↗

bioRxiv2023

Lipid network of plasma extracellular vesicles reveals sex-based differences in the lipidomic profile from patients with alcohol use disorder

Alcohol use disorder (AUD) is one of the most common psychiatric disorders, and the consumption of this substance is considered one of the main causes of preventable deaths worldwide. Lipids play a crucial functional role in cell membranes, however little is known about the role of lipids containing extracellular vesicles (EVs), as regulatory molecules and biomarkers. In this study, a highly sensitive lipidomic strategy is employed to characterize plasma EV lipid species from individuals with AUD, to evaluate differential functional roles and enzymatic activity networks to improve the knowledge of lipid metabolism in the alcohol consumption. Plasma EV lipids from female and male patients with AUD and healthy individuals were analyzed to obtain lipid differential abundance, as well as biological interpretation of LINEX2 lipidomics data, evaluating enzymatic dysregulation through an enrichment algorithm. Our results showed for the first time that females with AUD exhibit greater substrate-product changes in LPC and PC lipids, as well as phospholipases and acyltransferases activity, potentially linked to cancer progression and neuroinflammation. Conversely, males with AUD showed dysregulation in Cer and SM lipid, involving sphingomyelinases, sphingomyelin phosphodiesterase, and sphingomyelin synthase, which could be related with hepatotoxicity. Notably, females with AUD showed LION-terms associated with "positive intrinsic curvature", while males exhibited "negative intrinsic curvature, contributing to vesicle fusion processes. These methodological developments allow a better understanding of lipid metabolism and its regulatory mechanisms, which contributes not only to identify novel lipid targets, but also the discovery of sex-specific clinical biomarkers in the AUD.

pathology↗

bioRxiv2023

A comprehensive transcriptional signature in pancreatic ductal adenocarcinoma reveals new insights into the immune and desmoplastic microenvironment

Pancreatic ductal adenocarcinoma (PDAC) prognosis and treatment response remains devastatingly poor due partly to the highly heterogeneous, aggressive, and immunosuppressive nature of this tumor type. The intricate relationship between stroma, inflammation, and immunity remains vaguely understood in the PDAC microenvironment. Here, we performed a meta-analysis of stroma-, and immune-related gene expression in the PDAC microenvironment to improve disease prognosis and therapeutic development. We selected twenty-one PDAC studies from the Gene Expression Omnibus and ArrayExpress databases, including 922 samples (320 controls and 602 cases). Differential gene enrichment analysis identified 1153 significant dysregulated genes in PDAC patients that contribute to a desmoplastic stroma and an immunosuppressive environment (the hallmarks of PDAC tumors). The results highlighted two gene signatures related to the immune and stromal environments that cluster PDAC patients in high- and low-risk groups, impacting patient stratification and therapeutic decision-making. Moreover, HCP5, SLFN13, IRF9, IFIT2, and IFI35 immune genes were related to prognosis value in PDAC patients, for the first time. Simple SummaryPancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with few curative options. Desmoplastic stroma and immune system evasion in PDAC represent challenges to the success of therapeutic strategies that function well in other tumor types. Characterizing the PDAC microenvironment (including the immune environment) remains critical to developing safe and efficient therapies. Here, we present a comprehensive meta-analysis identifying 1153 significantly dysregulated genes, which mainly impact extracellular matrix remodeling and the immune system. We identify two signatures of twenty-eight immune-related genes and eleven stroma-related genes influencing PDAC patient survival. Additionally, five immune genes are associated with PDAC prognosis for the first time.

cancer biology↗

bioRxiv2022

ISCB RSG-Spain and highlights from the VIII Spanish Student Symposium in Bioinformatics and Computational Biology in 2021

The Regional Student Group of Spain is recognized by the Student Council and the International Society for Computational Biology. The objective of these institutions is to connect and share useful information among all professionals and students working in the field of bioinformatics and computational biology. In this article, we intend to present and publicize RSG-Spain, the Spanish ISCB regional student group, by relating its recent history of a growing community of students and young professionals and how it helps their development in the field. RSG-Spain, since its creation, has been involved in the organization of events with the aim of gathering bioinformaticians in the country and promoting research and collaboration in the field. Here the VIII Student Symposium held online in 2021 is presented, analyzing the output of the event and showing the main challenges found in its organization.

scientific communication and education↗