Biology subjects

Casals, G.

Publications and source records attributed to Casals, G..

4 recordsLinked to original sources

bioRxiv2025

Rapid quantification of short-chain fatty acids by Fourier-transform infrared spectroscopy for microbiota quality assessment

Short-chain fatty acids (SCFAs) are bacterial metabolites with crucial roles in host homeostasis and immune system modulation. Given their benefits, they have been proposed as markers of a healthy microbiota. Their quantification, however, is time-consuming, expensive and requires specialized personal and equipment. Thus, their use for quality assessment of stool samples in clinical contexts is limited. In this study we explored the use of Fourier-transform infrared (FT-IR) spectroscopy as an alternative method for metabolomic quality assessment of stool samples. FT-IR identifies the chemical bonds present in SCFAs and allows clear discrimination between healthy and dysbiotic stool samples (caused by Clostridioides difficile infection) through Principal Component Analysis (PCA). Overall, FT-IR provides a rapid, cost-effective and simple method for stool samples quality assessment. Combined with the widespread availability of this technology in most hospitals, these advantages highlight its potential application for routine implementation in clinical laboratories.

microbiology↗

bioRxiv2022

Merlin-deficient iPSCs show altered pluripotency and constitute a potential in vitro model for NF2-related schwannomas

NF2-related schwannomatosis is an autosomal dominant syndrome that predisposes to the development of benign tumors of the nervous system. Schwannomas, particularly bilateral vestibular schwannomas (VS), are the most characteristic features of the disease. These tumors are caused by the bi-allelic inactivation of the NF2 gene in a cell of the Schwann cell lineage. Our current understanding of the molecular pathogenesis of the NF2 gene, as well as the development of new effective therapies is hampered by the absence of human non-perishable cell-based bearing distinct NF2 pathogenic variants. With this aim, we generated and characterized three isogenic paired induced pluripotent stem cell (iPSC) lines with single or bi-allelic inactivation of NF2 by combining the direct reprogramming of VS cells with the use of CRISPR/Cas9 editing. Our results show a critical function of NF2 for the maintenance of a stable pluripotent state. However, we were able to nudge them towards the Neural Crest-Schwann Cell (NC-SC) axis by applying a 3D Schwann cell differentiation protocol. NF2(+/-) and NF2(-/-) spheroids homogeneously expressed classical markers of the NC-SC lineage. In addition, NF2(-/-) SC-like spheroids showed dysregulation of multiple signaling pathways already described for merlin-deficient SC, and altered in human schwannomas. Therefore, NF2(+/-) and NF2(-/-) SC-like spheroids can represent a bona fide human in vitro cellular model to study the role of NF2 pathogenesis.

cell biology↗

bioRxiv2020

Liver FoxO1 overexpression is positively associated with the degree of liver injury in cirrhotic patients

IntroductionChronic liver disease is associated with high mortality. Liver transplantation is the definitive treatment for patients with end-stage liver disease, improving their survival and quality of life. However, chronic rejection of the graft and the imbalance between the demand and the availability of organs limit its applicability. Therefore, finding therapeutic and/or diagnostic alternatives for these patients is a priority. In this context, preclinical studies in rodents have demonstrated that Akt plays a key role in liver dysfunction. Even with all this evidence, the activation status of Akt and its downstream targets in the liver of patients with chronic hepatopathy is still unknown. Hence, the present study aims to determine the activation status of the molecules involved in the Akt signaling pathway in livers of cirrhotic patients. Materials and MethodsIn this study, 36 liver tissue samples from a cohort of 27 cirrhotic patients and 9 patients without cirrhosis were included. A total of 10 proteins involved in Akt/mTOR pathway (GSK3{beta}, IGF1R, IRS1, mTOR, p70S6K, IR, PTEN, GSK3, TSC2, and RPS6) were analyzed using a multiplex immunoassay based on Luminex(R) technology. ResultsSignificant differences were found in several Akt/mTOR target proteins between the groups of cirrhotic patients vs. non-cirrhotic: FoxO1 (9.5 vs. 4.4; p<0.01), p-Akt (2.1 vs. 1.0; p<0.01), PTEN (3.061 vs. 1.877; p<0.05) and p70S6K (196.3 vs. 270.5; p<0.001). FoxO1 showed the best correlation with biochemical markers of liver injury aspartate aminotransferase and serum alanine aminotransferase (ASAT: r=0.51, p<0.05; ALAT: r=0.49, p<0.05). Moreover, the individual influence of FoxO1 on these parameters was confirmed by multiple regression analysis. It was the only enzyme in the Akt signaling pathway identified as a positive independent predictor of increased ASAT and ALAT levels. ConclusionFoxO1 is overexpressed in the liver of cirrhotic patients after partial hepatectomy. FoxO1 levels are also associated with the degree of liver injury, showing a positive correlation with current biomarkers used in clinical practice to detect liver injury.

cell biology↗

bioRxiv2020

Loss of the RNA helicase Dhx15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice

DHX15 is an ATP-dependent RNA helicase involved in pre-mRNA splicing and a downstream substrate for Akt1, which plays a significant role in vascular biology. The aim of this study was to explore the regulatory function of DHX15 over the vasculature and endothelial cell biology. Results: DHX15-/- was lethal in mouse and zebrafish embryos. DHX15-/- zebrafish also showed an undeveloped parachordal line, which leads to the formation of lymphatic structures. DHX15+/- mice triggered lower vascular network density and impaired lymphatic function postnatally. Transcriptome and proteome analysis of DHX15 silenced LEC revealed alterations in the glycolysis and gluconeogenesis pathways. The validation of these results demonstrated an uncoupling of the glycolysis with the oxidation of pyruvate in the mitochondria and a lower activity of the Complex I, resulting in lower cellular ATP production. Noteworthy, DHX15+/- mice partially inhibited primary tumor growth and reduced lung metastasis after injection of LLC1 tumor cells.

cell biology↗