https://hdl.handle.net/2072/478798 2026-04-15T04:35:12Z https://hdl.handle.net/2445/228875 Impacto del ejercicio intenso en los niveles de interleucina-6 en futbolistas semi-profesionales: un estudio comparativo entre adultos y niños. Reverter Masia, Joaquin; Cirer Sastre, Rafel; Jové Deltell, Carme; Corbi, Francisco; López Laval, Isaac; Hernández González, Vicenç El fútbol semi-profesional impone una gran demanda física, aumentando el riesgo de lesiones musculares debido a la acumulación de partidos y sesiones de entrenamiento con periodos de recuperación limitados. Este estudio evaluó los niveles de interleucina-6 (IL-6) en futbolistas semi-profesionales durante un partido de futbol siete, tanto en adultos como en niños. Se observó un notable aumento en los niveles de IL-6 tras un ejercicio de alta intensidad. La IL-6 no solo refleja una respuesta inflamatoria aguda, sino también una adaptación para mantener la homeostasis energética. Este incremento se asoció con una respuesta inflamatoria de fase aguda, evidenciada por el aumento de la intensidad del ejercicio. Aunque el ejercicio continuado mejora la eficiencia energética de los miocitos y podría reducir la liberación de IL-6, el ejercicio de alta intensidad en el fútbol semi-profesional parece superar estos efectos adaptativos. Esto subraya la necesidad de estrategias de recuperación adecuadas para mitigar el impacto del estrés físico acumulado y prevenir lesiones musculares. En conclusión, los niveles de IL-6 aumentan en respuesta al ejercicio intenso durante un partido de fútbol en jugadores semi-profesionales, tanto adultos como niños. Estos hallazgos destacan la importancia de monitorear IL-6 y otros marcadores inflamatorios para desarrollar estrategias efectivas de entrenamiento y recuperación. Futuros estudios deben investigar intervenciones que modulen la respuesta de IL-6 y optimicen la recuperación en atletas. 2026-04-13T17:20:15Z https://hdl.handle.net/2445/228859 Mixed-model and transcriptome-wide association analyses identify transcription factors and genes associated with colorectal cancer susceptibility Chen, Zhishan; Song, Wenqiang; Moreno Aguado, Víctor; Moratalla Navarro, Ferran Susceptibility transcription factors (TF) whose DNA bindings are altered by genetic variants regulating colorectal cancer (CRC) risk genes remain poorly defined. Using generalized linear mixed models, we analyze 218 TF ChIP-Seq datasets alongside GWAS data from 100,204 CRC cases and 154,587 controls of East Asian and European ancestries. We identify 51 TFs and TF-cofactor interactions, including VDR-cofactors, as key regulators of CRC risk. Integrating these TF insights with transcriptome-wide association studies (TWAS), we further evaluate associations between genetically predicted gene expression, alternative splicing, and alternative polyadenylation with CRC risk, using RNA-seq data from 364 Asian-ancestry and 707 European-ancestry individuals. Multi-ancestry TWAS identify 222 risk genes, including 95 novel genes and 48 potentially druggable targets. Single-cell analysis provides additional functional evidence supporting ~45% of these genes, and experimental validation confirms oncogenic roles for RHPN2, IRS2, and TXN. Our findings elucidate key TF–gene regulatory networks and uncover novel CRC risk genes. 2026-04-13T09:55:40Z https://hdl.handle.net/2445/228862 GTX-11 attenuates lung fibrosis, inflammation and vascular remodeling in preclinical models of lung fibrotic disease Montes Worboys, Ana; Milara, Javier; Farrera, Consol; Fernández Asensio, Cristina; Sánchez Díez, Silvia; Mercadé, Jaume; Montero, Paula; Roger, Inés; Molina Molina, María; Ruiz Cánovas, Eugenia; Cortijo, Julio Background: Fibrotic interstitial lung diseases (ILDs) are characterized by different degrees of inflammation and fibrosis of the lung parenchyma that are associated with progressive loss of breath, high morbidity and mortality. Current therapeutic options are limited, so there remains a significant need for effective and well-tolerated treatments. GTX-11 is an orally available small molecule in development for the treatment of fibrotic diseases. In this study, we aimed to assess the therapeutic potential of GTX-11 in different preclinical models of lung fibrotic disease.Methods: We assessed the activity of GTX-11 and its active metabolite, GTX-11m, in the bleomycin-induced pulmonary fibrosis model and in vitro in primary fibroblast cell cultures, including human normal lung fibroblasts (hNLFs) and ILD patient-derived fibroblasts.Results: In the murine model, GTX-11 treatment improved animal survival and significantly reduced lung fibrosis as measured by Ashcroft score and collagen deposition. GTX-11 also reduced the inflammatory cell count in bronchoalveolar lavage fluid and pro-inflammatory factors in lung tissue. Additionally, GTX-11 significantly improved lung vascular dysfunction and reduced pulmonary vascular remodeling. The preclinical anti-fibrotic effects of GTX-11 were comparable to, or in some cases exceeded, those of currently approved anti-fibrotic drugs used in clinical practice. In vitro, GTX-11m demonstrated anti-fibrotic and anti-inflammatory activity in hNLFs and ILD patient-derived fibroblasts. GTX-11m inhibited TGFβ-induced expression of key fibrotic markers and reduced fibroblast-to-myofibroblast transition and inflammatory cytokine production. The effects were consistent across the different tested ILD cultures and resulted from the prevention of SMAD2 and SMAD3 activation by TGFβ. The GTX‐11m anti-fibrotic and anti-inflammatory effects were comparable or better than nintedanib.Conclusion: Altogether, our studies reveal that GTX-11 is an effective antifibrotic both in vivo and in vitro, suggesting that GTX-11 has potential as a therapeutic option for fibrotic ILDs. 2026-04-13T11:17:08Z https://hdl.handle.net/2445/222781 Quality of life and experience of patients with heart failure with preserved ejection fraction and their caregivers Rubio, Raül; Palacios, Beatriz; Varela, Luis; Gutiérrez Ibañez, Martín; Camargo Correa, Selene; Calvo Barriuso, Elena; José Bazán, Nuria; Yun Viladomat, Sergi; Soria Gómez, María Teresa; Montero Hernández, Esther; Hidalgo, Encarna; Enjuanes, Cristina; Rueda, Yolanda; San Saturnino, Maite; Garcimartín Cerezo, Paloma; López Ibor, Jorge V.; Segovia Cubero, Javier; Comín Colet, Josep Background/Objectives: Evidence of patient experiences with heart failure with preserved ejection fraction (HFpEF) and disease impact on quality of life (QoL) is scarce. This study explored perceived impacts on QoL and healthcare experiences of HFpEF patients and their caregivers. Methods: This was a mixed-methods study with HFpEF patients, >= 40 years, New York Heart Association functional classes I-IV in Spain. Qualitative data were collected through semi-structured interviews with patients (n = 19) and caregivers (n = 17). The EuroQoL 5D-5L, Patient Global Impression of Severity, and Kansas City Cardiomyopathy Questionnaire were used to collect QoL measures. Results: The themes were as follows. (1) Impact of HFpEF on QoL; (2) new roles of informal caregiving; and (3) the increasing value of multidisciplinary care. Qualitative data were supported by a trend of worsening QoL on quantitative measures as HF progressed, despite quantitative measures not fully capturing the burden. Qualitative data further captured discrepancies of QoL perceptions. Conclusions: The impact of HFpEF on patients and their caregivers was similar to the HFrEF population's. Insights from discrepancies between PROMs data and interviews could help with tailoring QoL questionnaires to capture the broader impact of HFpEF, identify unmet needs, and customize care. 2025-08-27T06:57:50Z