Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype

Glioblastoma (GBM) represents one of the deadliest tumors owing to a lack of effective treatments. The adverse outcomes are worsened by high rates of treatment discontinuation, caused by the severe side effects of temozolomide (TMZ), the reference treatment. Therefore, understanding TMZ’s effects on GBM and healthy brain tissue could reveal new approaches to address chemotherapy side effects. In this context, we have previously demonstrated the membrane lipidome is highly cell type-specific and very sensitive to pathophysiological states. However, little remains known as to how membrane lipids participate in GBM onset and progression. Hence, we employed an ex vivo model to assess the impact of TMZ treatment on healthy and GBM lipidome, which was established through imaging mass spectrometry techniques. This approach revealed that bioactive lipid metabolic hubs (phosphatidylinositol and phosphatidylethanolamine plasmalogen species) were altered in healthy brain tissue treated with TMZ. To better understand these changes, we interrogated RNA expression and DNA methylation datasets of the Cancer Genome Atlas database. The results enabled GBM subtypes and patient survival to be linked with the expression of enzymes accounting for the observed lipidome, thus proving that exploring the lipid changes could reveal promising therapeutic approaches for GBM, and ways to ameliorate TMZ side effects.This study was supported in part by the Research Unit of the University Hospital Son Espases (“Ajuts a la Investigació de l’Hospital Son Espases 2017—Aplicación del lipidoma en el diagnóstico, pronóstico y tratamiento del glioma”), Basque Government (IT1162-19), the Institute of Health Carlos III (PI16/02200), and the EC (European Regional Development Fund, ERDF, CP12/03338). A.M.B. and J.B-E. hold predoctoral fellowships of the Govern Balear (Direcció General d’Innovació i Recerca, FPI/2160/2018 and FPI/1787/2015, respectively), co-funded by the ESF (European Social Fund). K.P.-R. contract was supported by the Govern Balear (Servei d’Ocupació de les IIles Balears and Garantia Juvenil, JQ-SP 18/17), co-funded by the ESF. G.B.-C.’s was supported by the Institute of Health Carlos III, co-funded by ERDF (Miguel Servet II program, CPII17/00005)

GDF15 and ACE2 stratify COVID-19 patients according to severity while ACE2 mutations increase infection susceptibility

Coronavirus disease 19 (COVID-19) is a persistent global pandemic with a very heterogeneous disease presentation ranging from a mild disease to dismal prognosis. Early detection of sensitivity and severity of COVID-19 is essential for the development of new treatments. In the present study, we measured the levels of circulating growth differentiation factor 15 (GDF15) and angiotensin-converting enzyme 2 (ACE2) in plasma of severity-stratified COVID-19 patients and uninfected control patients and characterized the in vitro effects and cohort frequency of ACE2 SNPs. Our results show that while circulating GDF15 and ACE2 stratify COVID-19 patients according to disease severity, ACE2 missense SNPs constitute a risk factor linked to infection susceptibility

Marcadores genéticos y el síndrome de apneas del sueño. Implicaciones fisiopatológicas

[spa] El Síndrome de la Apneas Obstructivas del Sueño es una enfermedad de alta prevalencia cuya manifestación clínica principal es la hipersomnia diurna que tiene un gran impacto social. Este síndrome se relaciona con un aumento significativo de la morbilidad cardiovascular, hipertensión arterial y sistémica, aumento del riesgo de accidente de tráfico y fallos cognitivos. También se asocia con mayor número de desórdenes metabólicos y una mayor respuesta inflamatoria. La estrecha relación del SAOS con la morbilidad cardiovascular (hipertensión, isquemia cardiaca, arritmias, infarto) hace que se haya convertido en un importante problema de salud pública. Existe una evidencia de una base genética para este síndrome aunque los genes específicos que influyen en su desarrollo aun no han sido identificados y hasta el momento se ha progresado poco en el conocimiento de la base genética del SAOS. Esta tesis doctoral identifica posibles polimorfismos que se relacionan con el síndrome y sus consecuencias fisiopatológicas

PolyunsaturatedFatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype

[eng] Glioblastoma (GBM) represents one of the deadliest tumors owing to a lack of effective treatments. The adverse outcomes are worsened by high rates of treatment discontinuation, caused by the severe side effects of temozolomide (TMZ), the reference treatment. Therefore, understanding TMZ's effects on GBM and healthy brain tissue could reveal new approaches to address chemotherapy side effects. In this context, we have previously demonstrated the membrane lipidome is highly cell type-specific and very sensitive to pathophysiological states. However, little remains known as to how membrane lipids participate in GBM onset and progression. Hence, we employed an ex vivo model to assess the impact of TMZ treatment on healthy and GBM lipidome, which was established through imaging mass spectrometry techniques. This approach revealed that bioactive lipid metabolic hubs (phosphatidylinositol and phosphatidylethanolamine plasmalogen species) were altered in healthy brain tissue treated with TMZ. To better understand these changes, we interrogated RNA expression and DNA methylation datasets of the Cancer Genome Atlas database. The results enabled GBM subtypes and patient survival to be linked with the expression of enzymes accounting for the observed lipidome, thus proving that exploring the lipid changes could reveal promising therapeutic approaches for GBM, and ways to ameliorate TMZ side effects. View Full-Tex