Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

URI permanent per a aquesta col·leccióhttps://hdl.handle.net/2445/7189

 Estadístiques

Examinar

Enviaments recents

Mostrant 1 - 20 de 556
  • Miniatura
    logoOpenAccessArticle
    New UB006 derivatives with a higher solubility and cytotoxic activity in ovarian cancer cells
    (MDPI, 2025-01-31) Reina del Pozo, Manuel; Ariza Piquer, Xavier; Serra i Cucurull, Dolors; García Gómez, Jordi; Herrero Rodríguez, Laura
    Background/Objectives: The compound (±)-UB006 ((4SR,5SR)-4 (hydroxymethyl)- 3-methylene-5-octyldihydrofuran-2(3H)-one) is a promising anti-cancer molecule. The enantiomer (–)-UB006 displays a potent cytotoxic effect in several tumor cell lines, particularly the ovarian cancer OVCAR-3 cell line, with a 40-fold increase in potency compared with the fatty acid synthase (FAS) inhibitor C75. Furthermore, in vivo, (–)-UB006 reduced the tumor burden in neuroblastoma xenografts. This effect was attributed to FAS inhibition and upregulation of apoptotic markers. However, CoA adducts of UB006 presented low solubility. Methods: We synthesized several (±)-UB006 derivatives by elongating the carbon chain of the primary alcohol and/or by adding hydroxyl groups with the aim of finding more potent and soluble anti-cancer compounds. Results: Our results showed a decrease in cytotoxicity when the carbon chain was elongated by more than two carbons. However, ethyl or propyl polyhydroxylated four-branched compounds showed an increased or maintained potency and solubility. The most promising compound was (±)-UB035 (IC50: 2.1 ± 0.2 µM), with a 2.5-fold increase in cytotoxicity in the OVCAR-3 cell line and a >4-fold increase in solubility (>2 mM) compared with (±)-UB006.
  • Miniatura
    logoOpenAccessArticle
    Yellow Fever in Latin America and the Escalating Risks in a Changing Eco-Epidemiological Landscape: A Review
    (Elsevier B.V., 2026-03-04) Ortiz-Prado, Esteban; Prieto-Marin, Jose G.; Izquierdo-Condoy, Juan S.; Vásconez González, Jorge Eduardo; Villamil Parra, Wilder; Viscor Carrasco, Ginés; Niño-Méndez, Óscar A.; Correa-Bautista, Jorge Enrique; Rusiñol Arantegui, Marta; Cevallos-Robalino, Doménica; Navarro, Juan Carlos; Villalobos-Madriz, Jorge A.
    Yellow fever (YF) remains a major public health concern in Latin America. We characterise the early-2025 outbreak, compare it with prior waves—especially Southeast Brazil (2016–2018)—and examine environmental, structural, and policyrelated drivers. We reviewed regional surveillance data and mortality records from January to April 2025, comparing them to historical outbreak data. Case fatality rates (CFR), geographic spread, and population vulnerability patterns were analyzed. We also reviewed published literature and health alerts to contextualize contributing factors. In 2025, 301 confirmed cases and 124 deaths were reported (CFR 41.1%), mostly in Bolivia, Brazil, Colombia, and Peru, concentrated among unvaccinated populations at the forest–urban interface. Transmission remains sylvatic, but peri-urban spillover risk is rising. Deforestation, climate variability, cross-border migration, and political instability heighten vulnerability; surveillance is fragmented and vaccine uptake insufficient in high-risk groups. YF is re-emerging through intertwined biological, ecological, and socio-political forces. Preventing another large-scale epidemic requires strengthened, integrated surveillance, including Non-Human Primates (NHP) epizootics, equity-centred immunisation in remote areas, and coordinated regional action focused on prevention, early detection, and health-system resilience.
  • Miniatura
    logoOpenAccessArticle
    Licochalcone A prevents cognitive decline in a lipopolysaccharide‑induced neuroinflammation mice model
    (BioMed Central, 2025-12-01) Carrasco, Marina (Carrasco Pérez); Guzman, Laura; Olloquequi, Jordi; Cano Fernández, Amanda; Fortuna, Ana; Vázquez Carrera, Manuel; Verdaguer Cardona, Ester; Auladell i Costa, M. Carme; Ettcheto Arriola, Miren; Camins Espuny, Antoni
    Inflammation plays a key role in the development of neurodegenerative disorders that are currently incurable. Licochalcone A (LCA) has been described as an emerging anti-inflammatory drug with multiple therapeutical properties that could potentially prevent neurodegeneration. However, its neuroprotective mechanism remains unclear. Here, we investigated if LCA prevents cognitive decline induced by Lipopolysaccharide (LPS) and elucidated its potential benefits. For that, 8-week-old C57BL6/J male mice were intraperitonially (i.p.) treated with saline solution or LCA (15 mg/kg/day, 3 times per week) for two weeks. The last day, a single i.p injection of LPS (1 mg/kg) or saline solution was administered 24 h before sacrifice. The results revealed a significant reduction in mRNA expression in genes involved in oxidative stress (Sod1, Cat, Pkm, Pdha1, Ndyfv1, Uqcrb1, Cycs and Cox4i1), metabolism (Slc2a1, Slc2a2, Prkaa1 and Gsk3b) and synapsis (Bdnf, Nrxn3 and Nlgn2) in LPS group compared to saline. These findings were linked to memory impairment and depressive-like behavior observed in this group. Interestingly, LCA protected against LPS alterations through its anti-inflammatory effect, reducing gliosis and regulating M1/M2 markers. Moreover, LCA-treated animals showed a significant improvement of antioxidant mechanisms, such as citrate synthase activity and SOD2. Additionally, LCA demonstrated protection against metabolic disturbances, downregulating GLUT4 and P-AKT, and enhanced the expression of synaptic-related proteins (P-CREB, BDNF, PSD95, DBN1 and NLG3), leading all together to dendritic spine preservation. In conclusion, our results demonstrate that LCA treatment prevents LPS-induced cognitive decline by reducing inflammation, enhancing the antioxidant response, protecting against metabolic disruptions and improving synapsis related mechanisms.
  • Miniatura
    logoOpenAccessArticle
    Impact of hormonal contraceptives on exercise physiology and athletic performance across the contraceptive cycle. A pilot study
    (Elsevier, 2026-07-07) Piñol-Granadino, Nil; Rotllan, Cristina; Viscor Carrasco, Ginés
    Background: Historically, research in exercise physiology has tended to overlook women, focusing mostly on studies involving men and disregarding female hormonal variations, including the effects of commonly used hormonal contraceptives among athletes. The influence of exogenous hormones could affect health and athletic performance, besides providing a stable hormonal environment to assess the acute effects of sexual hormones on physiological variables and performance. These potential impacts are critical to guide training strategies for female athletes.Hypothesis: Hormonal contraceptives affect physiological responses and athletic performance in healthy young women and elite athletes. It is hypothesized that during the inactive phase, aerobic and anaerobic exercise, as well as strength, would be superior compared to the active phase. Materials and Methods: Longitudinal observational study with repeated measures exploring physiological responses in five elite athletes, all using hormonal contraceptives. Variables including lactate, heart rate, and power output were evaluated during a submaximal 2000-meter rowing ergometer test, assessed during two phases of the contraceptive cycle. Results: Baseline characteristics were described. No significant differences were observed in physiological variables between the two phases of the hormonal contraceptive cycle. Conclusions: There were no significant differences in performance between active and inactive phases of hormonal contraceptives. Variations in physiological parameters among studies suggest the need for an individualized approach. Future studies should use larger samples and rigorous methodologies to clarify effects of the contraceptive use on athletes.
  • Miniatura
    logoOpenAccessArticle
    Higher Prevalence of Cognitive Impairment in Residents of High-Altitude Regions
    (MDPI, 2026-06-24) Merma-Valero, Judith Marie; Ccorimanya-Suni, Rocio Milagros; Pancaya-Flores Maria Emilia; Guevara-Mamani, Zhenia Milagros; Chambi-Rodrigo, Doris; Coa-Coila, Mahely Adriana; Cruz-Riquelme, Tatiana Milagros; Bernedo Itusaca, Margot Evelin; Apaza-Cansaya, Wilma; Apaza-Quispe, Mirian Milagros; Hancco-Monrroy, Dante Elmer; Loayza Coila, Carlos Angel; Salazar Granara, Alberto; Yang, Mingming; Viscor Carrasco, Ginés; Hancco Zirena, Ivan
    Introduction: A major health issue in individuals living at high-altitude regions is an increase in the number of red blood cells (RBCs). This condition generates a series of physiological alterations including the nervous system, where damage can occur due to increased blood viscosity. This increased viscosity, in turn, could compromise oxygen uptake, potentially linked to a degree of cognitive impairment. Objective: To determine the association between exposure to chronic hypoxia and sleep quality with the degree of cognitive impairment in a young adult population residing at different altitude levels. Methodology: A cross-sectional study was conducted with 200 apparently healthy subjects (aged 21–26 years) permanently residing in four Peruvian cities: Lima (154 m), Arequipa (2,335 m), Puno (3,820 m), and La Rinconada (5,100 m) (n= 50 per location). Physiological profiles (SpO , blood pressure, heart rate, hemoglobin, and hematocrit) were measured. Cognitive impairment and sleep quality were evaluated using the Montreal Cognitive Assessment (MoCA) and the Pittsburgh Sleep Quality Index (PSQI). Sex-stratified hierarchical multiple linear regression models with bootstrapping were utilized for independent correlation analysis. Results: Hemoglobin levels gradually increased with altitude, peaking at 19.47 ± 3.01 g/dL in La Rinconada, while SpO2 decreased to 81.64%. Moderate-to-severe cognitive impairment was exclusively restricted to the extreme altitude population of La Rinconada, where only 10% of subjects remained unaffected. In the sex-stratified multivariate regression, residency in La Rinconada initially served as a robust negative predictor of MoCA scores among women (β = −5.52, p < 0.001); however, this geographical effect lost statistical significance after adjusting for biological variables in Model 2 (β = −4.72, p = 0.178). In the fully adjusted models, neither individual hemoglobin levels nor SpO2 fluctuations displayed an independent linear association with cognitive performance in either sex (p > 0.05). Sleep quality was poor across cohorts but showed no significant association with cognitive impairment (p = 0.174). Conclusions: Chronic exposure to severe hypoxia (>5000 m) is associated with a greater presence of cognitive impairment, which is largely accounted for by individual physiological adaptations rather than isolated, linear effects of independent hematological or subjective sleep parameters [M1]Please confirm if the bold formatting is necessary; if not, please remove it. The following highlights are the same. [M2]Please confirm whether “n” is a variable and should therefore appear in italics. If yes, please revise in the whole text. [M3]Please check if 2 should be subscript. If yes, please revise in the whole text.
  • Miniatura
    logoOpenAccessArticle
    Quantifying the Global Population Residing at Different Altitudes
    (Frontiers Media, 2026-05-08) Ortiz-Prado, Esteban; Izquierdo-Condoy, Juan S.; Vasconez-González, Jorge; Salazar-Santoliva, Camila; Teo, Terence K.; Lopez-Cortes, Andres; Viscor Carrasco, Ginés
    Human adaptation to low oxygen at high altitudes has been extensively studied, with adaptations categorized as metabolic or respiratory. Altitudes are commonly classified into different ranges (low,18 moderate, high, and very high), yet quantifying the global population exposed to these elevations remains challenging due to population dynamics. This study aimed to quantify the global population living at different altitude ranges and to describe its distribution using geospatial and population databases. We conducted a global ecological analysis using data from the World Cities Database (Pro version, refreshed May 11, 2025), GPS elevation data from the dCode tool, and NASA’s Shuttle Radar Topography Mission (SRTM). Over 1.8 million cities were classified according to two altitude categorizations: the classical classification of low (<2,500 m) and high (≥2,500 m) altitudes, and the International Society for Mountain Medicine (ISMM) classification (low: <1,500 m, moderate: 1,500–2,500 m, high: 2,500–3,500 m, very high: 3,500–5,500 m). The analysis revealed that 99.26% of the global population (~7.95 billion) lives below 2,500 meters, where 98.86% of cities are located. In contrast, only 0.74% of the population (~57.8 million) resides above 2,500 meters, with significant concentrations in the Andes, Himalayas, and Ethiopian Highlands. Population density declines sharply as altitude increases. The vast majority of the global population resides below 2,500 meters. These findings provide a crucial foundation for understanding how altitude influences population distribution and highlight the need for further research into the health impacts of high-altitude living. This study offers insights for public health strategies aimed at mitigating altitude related health risks.
  • Miniatura
    logoOpenAccessArticle
    Effects of the Edible Microalga Chlorella on Gut Microbiota and on Brain Health: Current Evidence and Emerging Links
    (MDPI, 2026-06-21) Felip, Olga; García Alday, Iker; Santocildes Martinez, Garoa; Torrella Guio, Joan Ramon; Viscor Carrasco, Ginés; Torres, Josep Lluis; Ramos Romero, Sara
    Background: Chlorella. a unicellular green alga, is currently one of the most popular algae supplements due to its high content of bioactive compounds. Chlorella’s wide range of macro- and micronutrients, including chlorophyll compounds and carotenoids, has been suggested to influence various disorders related to the digestive and nervous systems. This review’s primary purpose was to critically analyze the effects of Chlorella intake on gut microbiota and brain function. Methods: The authors conducted a systematic review with narrative synthesis of peer-reviewed articles written in English and published in PubMed, Web of Science, and Scopus spanning the years 2009 to 2026 (PROSPERO registration number CRD42024527705). The search protocol was performed following PRISMA guidelines. Primary outcomes encompassed physiological variables, such as gut microbial composition, short-chain fatty acids, brain-derived neurotrophic factor, and hippocampal cell density. Secondary outcomes were assessed through neurobehavioral tests and psychological questionnaires. Results: Out of the 1333 articles identified, 47 studies were deemed eligible, and 21 met the predefined criteria, subsequently incorporated into this systematic review. In total, 10 articles documented interventions involving Chlorella and their effects on the gut microbiota, whereas 11 articles investigated several variables pertinent to brain function. Most of the studies included were conducted in animal models, with only a limited number of human trials. Nineteen studies (90%), predominantly preclinical, reported positive associations between Chlorella consumption, gut microbiota modulation, and physiological or neurobehavioral markers related to the gut–brain axis. Conclusions: Chlorella consumption may modulate gut microbiota composition and function, potentially influencing brain-related processes. However, the available literature lacks studies simultaneously addressing both gut microbiota and brain health parameters limiting the understanding of the underlying physiological mechanisms.
  • Miniatura
    logoOpenAccessArticle
    Nrf2 and oxidative stress in liver ischemia/reperfusion injury
    (Wiley, 2021-12-30) Bardallo, Raquel G.; Panisello Roselló, Arnau; Sánchez Nuño, Sergio; Alva, Norma; Roselló Catafau, Juan; Carbonell i Camós, Teresa
    In response to stress signal, nuclear factor-erythroid 2-related factor 2 (Nrf2) induces the expression of target genes involved in antioxidant defense and detoxification. Nrf2 activity is strictly regulated through a variety of mechanisms, including regulation of Keap1-Nrf2 stability, transcriptional regulation (NF-ĸB, ATF3, ATF4), and post-transcriptional regulation (miRNA), evidencing that transcriptional responses of Nrf2 are critical for the maintenance of homeostasis. Ischemia-reperfusion (IR) injury is a major cause of graft loss and dysfunction in clinical transplantation and organ resection. During the IR process, the generation of reactive oxygen species (ROS) leads to damage from oxidative stress, oxidation of biomolecules, and mitochondrial dysfunction. Oxidative stress can trigger apoptotic and necrotic cell death. Stress factors also result in the assembly of the inflammasome protein complex and the subsequent activation and secretion of proinflammatory cytokines. After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense against the cytotoxic effects of oxidative stress and help to promote hepatic recovery during IR. The complex crosstalk between Nrf2 and cellular pathways in liver IR injury and the potential therapeutic target of the Nrf2 inducers will be discussed in the present review.
  • Miniatura
    logoOpenAccessArticle
    The central clock drives metabolic rhythms in muscle stem cells
    (Elsevier, 2025-10-28) Sica, Valentina; Smith, Jacob G.; Deryagin, Oleg; Andrés, Eva; Lukesova, Vera; Egg, Mirijam; Cabezas-Wallscheid, Nina; Aznar Benitah, Salvador; Serrano, Antonio L.; Perdiguero, Eusebio, 1968-; Muñoz Cánoves, Pura, 1962-
    Satellite cells (SCs), the skeletal muscle resident stem cells, maintain a state of quiescence yet exhibit robust circadian oscillations at the transcriptional level. How SC circadian rhythms are controlled is not well understood. Here, we use SC-specific reconstitution of the essential clock gene Bmal1 in mice to elucidate the role of the local SC clock and its interplay with the central clock in the brain. We find that 24-h rhythmicity of metabolic genes in SCs depends on central clock inputs, independent of the SC clock, and identify rhythmic feeding-fasting cycles as the key brain clock-dependent output controlling their oscillation. Functionally, central signals regulate SC metabolic state and SC-mediated muscle repair, and we identify intact autophagic function as a prerequisite for correct oscillation of metabolic transcripts. Overall, we show that the central clock acts dominantly via feeding-fasting cycles to control rhythmic gene expression and metabolic state in quiescent SCs.
  • Miniatura
    logoOpenAccessArticle
    Chaperone-Mediated Autophagy in fish: a key function amid a changing environment.
    (Taylor & Francis, 2024) Schnebert, Simon; Vélez, Emilio J.; Goguet, Maxime; Dias, Karine; Véron, Vincent; García-Pérez, Isabel; Radler, Lisa M.; Cardona, Emilie; Fontagné-Dicharry, Stéphanie; Van Delft, Pierre; Dittrich-Domergue, Franziska; Bernard, Amélie; Beaumatin, Florian; Herpin, Amaury; Cleveland, Beth; Seiliez, Iban
    Chaperone-Mediated Autophagy (CMA) is a major pathway of lysosomal proteolysis critical for cellular homoeostasis and metabolism. While extensively studied in mammals, CMA's existence in fish has only been confirmed recently, offering exciting insights into its role in species facing environmental stress. Here, we shed light on the existence of 2 genes encoding the CMA-limiting factor Lamp2A (lysosomal associated membrane protein 2A) in rainbow trout (RT, Oncorhynchus mykiss), revealing distinct expression patterns across various tissues. Notably, RT lacking the most expressed Lamp2A exhibit profound hepatic proteome disturbances during acute nutritional stress, underscoring its pivotal role as a guardian of hepatic proteostasis. Building upon these findings, we introduce and validate the CMA activation score as a reliable indicator of CMA status, providing a valuable tool for detecting cellular stress in fish under environmental threats. Overall, our study offers new perspectives into understanding CMA from evolutionary and environmental contexts.
  • Miniatura
    logoOpenAccessArticle
    Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimers disease in metabolically stressed APPswe/PS1dE9 mice
    (BioMed Central, 2021-07-22) Ettcheto Arriola, Miren; Sánchez López, E. (Elena); Cano Fernández, Amanda; Carrasco, Marina (Carrasco Pérez); Herrera, Katherine; Manzine, Patricia; Espinosa Jiménez, Triana; Busquets Figueras, Oriol; Verdaguer Cardona, Ester; Olloquequi, Jordi; Auladell i Costa, M. Carme; Folch, Jaume; Camins Espuny, Antoni
    Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg-1 d-1) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. Results: Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. Conclusions: Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy.
  • Miniatura
    logoOpenAccessArticle
    ARMCX3 mediates susceptibility to hepatic tumorigenesis promoted by dietary lipotoxicity.
    (MDPI, 2021-03-05) Mirra, Serena; Gavaldà i Navarro, Aleix; Manso Sanz, Yasmina; Higuera, Mónica; Serrat Reñé, Román; Salcedo Allende, María Teresa; Burgaya i Márquez, Ferran; Balibrea, José; Santamaría, Eva; Uriarte, Iker; Berasain, Carmen; Avila, Matías A.; Mínguez, Beatriz; Soriano García, Eduardo; Villarroya i Gombau, Francesc
    Abstract: ARMCX3 is encoded by a member of the Armcx gene family and is known to be involved in nervous system development and function. We found that ARMCX3 is markedly upregulated in mouse liver in response to high lipid availability, and that hepatic ARMCX3 is upregulated in pa-tients with NAFLD and hepatocellular carcinoma (HCC). Mice were subjected to ARMCX3 in-validation (inducible ARMCX3 knockout) and then exposed to a high-fat diet and diethylnitrosa-mine-induced hepatocarcinogenesis. The effects of experimental ARMCX3 knockdown or overex-pression in HCC cell lines were also analyzed. ARMCX3 invalidation protected mice against high-fat-diet-induced NAFLD and chemically induced hepatocarcinogenesis. ARMCX3 invalida-tion promoted apoptotic cell death and macrophage infiltration in livers of diethylnitrosa-mine-treated mice maintained on a high-fat diet. ARMCX3 downregulation reduced the viability, clonality and migration of HCC cell lines, whereas ARMCX3 overexpression caused the reciprocal effects. SOX9 was found to mediate the effects of ARMCX3 in hepatic cells, with the SOX9 inter-action required for the effects of ARMCX3 on hepatic cell proliferation. In conclusion, ARMCX3 is identified as a novel molecular actor in liver physiopathology and carcinogenesis. ARMCX3 downregulation appears to protect against hepatocarcinogenesis, especially under conditions of high dietary lipid-mediated hepatic insult.
  • Miniatura
    logoOpenAccessArticle
    Characterization of the composition and immunoregulatory activity of wheat cell culture-derived polysaccharides
    (MDPI, 2026-05-06) Murtazina, Alima; Rodríguez-Martínez, Pol; Crawshaw, Dylan J.; Caelles Franch, Carme; Tarabayeva, Anel; Bitanova, Elmira; Ibragimova, Nadezhda; Mikshina, Polina; Gorshkova, Tatyana; McDougall, Gordon J.; Boulaiz, Houria; Bishimbayeva, Nazira; Valledor Fernández, Annabel
    Plant polysaccharides can exert immunomodulatory activities. In this study we provided chemical characterization of wheat cell culture-derived polysaccharides (WCCPS) and assessed their capacity to modulate inflammatory responses in mouse macrophages. The total sample (T-010) contained arabinogalactans, arabinans, glucans and xyloglucans. Fractionation by anion-exchange chromatography rendered a bound acidic fraction (B-010) and an unbound neutral fraction (UB-010). The B-010 fraction was enriched in arabinogalactans and arabinans, with some galactans, homogalacturonans, and arabinoxylans. The neutral UB-010 fraction was composed of glucans and xyloglucans. None of the WCCPS preparations triggered cytokine production on their own, but each potentiated different macrophage responses to bacterial lipopolysaccharide (LPS). The total WCCPS in T-010 increased LPS-induced tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 secretion, whereas the acidic arabinogalactan-rich fraction B-010 boosted IL-6 release and selectively upregulated nitric oxide synthase 2 (Nos2) and cholesterol 25-hydroxylase (Ch25h) expression in response to LPS. In contrast, the neutral UB-010 fraction enhanced IL-6 levels and induced Nos2 expression without altering Ch25h expression. These results suggest that WCCPS can modulate distinct aspects of the inflammatory response, with their effects shaped by their composition and structural features. Future research will focus on elucidating the molecular mechanisms underlying the immunomodulatory activity of WCCPS.
  • Miniatura
    logoOpenAccessArticle
    G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials
    (Wiley, 2025-01-06) Bellver Sanchis, Aina; Ribalta Vilella, Marta; Irisarri, Alba; Gehlot, Pinky; Choudhary, Bhanwar Singh; Jana, Abhisek; Vyas, Vivek Kumar; Banerjee, Deb Ranjan; Pallàs i Llibería, Mercè, 1964-; Guerrero López, Ana; Griñán Ferré, Christian
    This review provides a comprehensive overview of the role of G9a/EHMT2, focusing on its structure and exploring the impact of its pharmacological and/or gene inhibition in various neurological diseases. In addition, we delve into the advancements in the design and synthesis of G9a/EHMT2 inhibitors, which hold promise not only as a treatment for neurodegeneration diseases but also for other conditions, such as cancer and malaria. Besides, we presented the discovery of dual therapeutic approaches based on G9a inhibition and different epigenetic enzymes like histone deacetylases, DNA methyltransferases, and other lysine methyltransferases. Hence, findings offer valuable insights into developing novel and promising therapeutic strategies targeting G9a/EHMT2 for managing these neurological conditions.
  • Miniatura
    logoOpenAccessArticle
    NRF2 deficit prevents pathologic Tau seeding and spreading in an induced tauopathy mouse model
    (Elsevier B.V., 2026-02-05) López-Sampere, Yaiza; Mengod, Pol; Roca-Pereira, Sergio; Vinyals, Antònia; Mato-Blanco, Xoel; Vela-Martínez, Marta; Dakterzada, Farida; Romero, Leila; Santamaría Martínez, Enrique; Fernández Irigoyen, Joaquín; Ferrer, Isidro (Ferrer Abizanda); Povedano Panades, Mónica; Río Fernández, José Antonio del; Santpere Baró, Gabriel; Portero Otin, Manuel; Piñol Ripoll, Gerard; Andrés-Benito, Pol
    Background Nuclear factor erythroid 2–related factor 2 (NRF2) regulates antioxidant defenses and protects against neurodegeneration, including Alzheimer's disease (AD). Its age-related decline disrupts redox balance and increases neuronal vulnerability, but the early hippocampal effects remain unclear. Here, we tested whether NRF2 loss affects tau seeding and spreading in a PHF-tau–inoculated mouse model, contributing to accelerated aging. Methodology Three-month-old NRF2-knockout (Nfe2l2−/−) and wild-type (WT) mice received hippocampal inoculations of human AD-derived PHF-tau, and tau propagation was analyzed after three months. To elucidate the molecular underpinnings of the observed changes, we performed integrative phosphoproteotranscriptomic analyses of hippocampal tissue, supported by RT-qPCR and Western blot validation. Results PHF-tau inoculation at 3 months of age in Nfe2l2−/− mice, surprisingly, exhibited markedly reduced tau seeding and spreading compared to WT after 3 months of incubation. Molecular characterization of the Nfe2l2−/− hippocampus was carried out to unravel the molecular changes associated with impaired tau propagation. Transcriptomic profiling revealed 745 deregulated genes in Nfe2l2−/− mice, characterized by upregulation of immune and metabolic pathways but downregulation of oxidative stress and redox-related genes. RT-qPCR confirmed diminished expression of antioxidant enzymes and anti-inflammatory receptors, alongside altered astrocytic markers. Proteomic analysis identified 157 dysregulated proteins associated with mitochondrial, synaptic, and inflammatory processes, while phosphoproteomics detected 824 altered phosphosites enriched in cytoskeletal and synaptic networks. Western blot showed increased GFAP-C-term, AQP4, 8-OHdG, and MDAL, with reduced GSTM2 expression. Notably, total and 4R-tau levels were decreased, while 3R-tau was elevated in Nfe2l2−/− mice. Conclusion Our findings suggest that NRF2 loss induces a hippocampal state marked by impaired antioxidant defenses, astrocytic remodeling, and disrupted tau isoform balance. This environment, while metabolically altered, paradoxically hinders tau propagation, highlighting NRF2 as a key regulator of both redox and cellular maturity programs essential for tau spread and as a potential therapeutic target in tauopathies.
  • Miniatura
    logoOpenAccessArticle
    Acidogenic fermentation of biowaste coupled with nitrogen recovery using selective membranes to produce a VFA-rich liquid with a high C/N ratio
    (Elsevier Ltd., 2024) Peña Picola, Sergi; Serra Toro, Andreu; Da Silva, C.; Peces, Miriam; Jordán, Maria; Vila Grajales, Joaquim; Grifoll Ruiz, Magdalena; Valentino, Francesco; Astals Garcia, Sergi; Dosta Parras, Joan
    This research focuses on the production of a liquid stream rich in volatile fatty acids (VFAs) and low ammoniacal nitrogen content (<0.1 g N/L) from biowaste. The liquid stream was obtained by combining (i) mixed culture acidogenic fermentation to maximise VFA production and (ii) gas-permeable membrane (GPM) contactor to recover ammoniacal nitrogen. Three batch fermentation tests of biowaste collected in a full-scale mechanical-biological treatment plant provided high and stable VFA concentrations (37–39 g CODVFA/L). VFAs represented 73–81 % of the soluble chemical oxygen demand (sCOD) concentration, with a predominance of acetic, propionic and butyric acids. A highly specialized microbial community was observed in all batch tests, with Bacteroidota and Firmicutes as predominant phyla (>90 % of relative abundance). The GPM contactor recovered more than 99 % of the ammoniacal nitrogen in the fermentation liquid without VFA losses. The suitability of the produced fermentation liquid with a high C/N ratio for downstream applications was evaluated using biomethane potential tests (BMP) at different total ammonium nitrogen (TAN) concentrations (0.76–3.15 g N/L) and circumneutral pH. Despite achieving similar ultimate methane yields (279–314 NmL CH4/g CODfeed), lower TAN concentrations in the biowaste fermentation liquid improved anaerobic biodegradation kinetics, enhancing its potential applicability for methane production.
  • Miniatura
    logoOpenAccessArticle
    Sustained exercise improves growth performance and reduces fat deposition in gilthead sea bream juveniles fed with a high-protein and a high-carbohydrate diet
    (Elsevier B.V., 2024-04-25) García-Pérez, Isabel; Montblanch, Manel; Sánchez-Moya, Albert; Perelló-Amorós, Miquel; Otero-Tarrazón, Aitor; Fernández Borrás, J. (Jaume); Blasco Mínguez, Josefina; Gutiérrez Fruitós, Joaquín
    In gilthead sea bream (Sparus aurata), sustained exercise induces metabolic and endocrine adaptations towards more efficient utilization of dietary nutrients and better growth performance. This work aims to examine in this species the combined effects of swimming activity (voluntary swimming vs. exercise) and diet composition (highprotein diet vs. high-carbohydrate diet) on growth performance, muscle composition, flesh texture, and gene expression of growth hormone (Gh)/insulin-like growth factors (Igfs) axis members and muscle development markers. After 6 weeks of experiment, fish subjected to sustained exercise exhibited enhanced growth performance and reduced muscle lipid content, mesenteric fat and hepatosomatic index compared to those in voluntary swimming. Also, exercised fish fed with the high-protein diet showed the highest final body weight. Unexpectedly, exercise appeared to reduce flesh texture parameters, mainly elasticity. Regarding the gene expression, the hepatic levels of the anabolic Gh receptor (ghr-1) were significantly higher in the exercised fish fed with the high-protein diet compared to other groups. The high-protein diet increased the gene expression of different molecules of the Gh/Igfs axis in liver (igf-1, igf-2, igfbp-2b, igfbp-4, igfbp-5b, igf-1rb, akt-2) and akt-2 in muscle, suggesting a better anabolic endocrine state. In muscle, the proteolytic systems’ gene expression was not affected by either swimming activity or diet composition, but the high-protein diet upregulated the transcription of myogenic and proliferative markers like pcna, myf5 and myod2. Overall, these results highlight the positive effects of exercise on growth performance and lipid reserves utilization in gilthead sea bream juveniles, suggesting exercise as a valuable tool when formulating protein-adjusted diets for this species.
  • Miniatura
    logoOpenAccessArticle
    Effect of different types of supervised exercise programs on cardiorespiratory and muscular fitness, pain, fatigue, mental health and inflammatory and oxidative stress biomarkers in older patients with post-COVID-19 sequelae “EJerSA-COVID-19”: a randomized controlled trial.
    (BioMed Central, 2023-12-15) Miravitlles Fernández, Marc; Serra Prat, Mateu; Viñals, Xavier; Girabent i Farrés, Montserrat; Carbonell i Camós, Teresa; Garnacho Castaño, Manuel Vicente; Pleguezuelos Cobo, Eulogio; Sánchez Nuño, Sergio; Carmen, Amin Del; Serra Paya, Noemí; Moreno, Eva; Molina Raya, Lorena, 1979-; Robleda, Gemma; Benet, Marta; Santos-Ruiz, Susana; Biurrun Garrido, Ainoa; Jerez Molina, Carmen
    Background: Many patients with COVID-19 present the so-called post-acute sequelae of COVID-19 such as fatigue, post-stress discomfort, dyspnea, headache, pain mental impairment, incapacity to perform daily physical tasks ant exercise intolerance. This study aims to investigate the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. Methods: The sample will be made up of 120 eligible participants, over the age of 60 years who have had COVID-19 disease and are survivors and present persistent COVID-19 symptomatology diagnosed by the corresponding physician. The participants will be randomly assigned to the experimental groups: supervised endurance group (SEG, n = 30), supervised strength group (SSG, n = 30), supervised concurrent group (SCG, n = 30), which will perform the corresponding exercise program 3 days a week compared to the control group (CG, n = 30), which will not carry out a supervised exercise program. The design of this project will include measurements of four relevant dimensions; 1) Cardiorespiratory fitness; 2) Muscle fitness; 3) Pain and mental health; and 4) Biomarkers of inflammation and oxidative stress. Conclusions: The results of this study will provide insights into the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. These findings may be the basis for the formulation of health plans and rehabilitation programs that allow healthy aging and a reduction in the associated morbidity in patients with post-COVID-19 sequelae.
  • Miniatura
    logoOpenAccessArticle
    Mitochondrial adaptation to diet and swimming activity in Gilthead Seabream: Improved nutritional efficiency.
    (Frontiers Media, 2021-06-18) Perelló-Amorós, Miquel; Fernández Borrás, J. (Jaume); Sánchez-Moya, Albert; Vélez, Emilio J.; García-Pérez, Isabel; Gutiérrez Fruitós, Joaquín; Blasco Mínguez, Josefina
    Sustained exercise promotes growth in different fish species, and in gilthead seabream we have demonstrated that it improves nutrient use efficiency. This study assesses for differences in growth rate, tissue composition and energy metabolism in gilthead seabream juveniles fed two diets: high-protein (HP; 54% protein, 15% lipid) or high energy (HE; 50% protein, 20% lipid), under voluntary swimming (VS) or moderate-to-low-intensity sustained swimming (SS) for 6 weeks. HE fed fish under VS conditions showed lower body weight and higher muscle lipid content than HP fed fish, but no differences between the two groups were observed under SS conditions. Irrespective of the swimming regime, the white muscle stable isotopes profile of the HE group revealed increased nitrogen and carbon turnovers. Nitrogen fractionation increased in the HP fed fish under SS, indicating enhanced dietary protein oxidation. Hepatic gene expression markers of energy metabolism and mitochondrial biogenesis showed clear differences between the two diets under VS: a significant shift in the COX/CS ratio, modifications in UCPs, and downregulation of PGC1a in the HE-fed fish. Swimming induced mitochondrial remodeling through upregulation of fusion and fission markers, and removing almost all the differences observed under VS. In the HE-fed fish, white skeletal muscle benefited from the increased energy demand, amending the oxidative uncoupling produced under the VS condition by an excess of lipids and the pro-fission state observed in mitochondria. Contrarily, red muscle revealed more tolerant to the energy content of the HE diet, even under VS conditions, with higher expression of oxidative enzymes (COX and CS) without any sign of mitochondrial stress or mitochondrial biogenesis induction. Furthermore, this tissue had enough plasticity to shift its metabolism under higher energy demand (SS), again equalizing the differences observed between diets under VS condition. Globally, the balance between dietary nutrients affects mitochondrial regulation due to their use as energy fuels, but exercise corrects imbalances allowing practical diets with lower protein and higher lipid content without detrimental effects.
  • Miniatura
    logoOpenAccessArticle
    Adult-specific Reelin expression alters striatal neuronal organization. Implications for neuropsychiatric disorders. 
    (Frontiers Media, 2022-02-22) Pardo Muñoz, Mónica; Gregorio Jordán, Sara; Montalban, Enrica; Pujadas Puigdomènech, Lluís; Elias-Tersa, Alba; Vílchez Acosta, Alba del Valle; Parent, Annabelle; Auladell i Costa, M.Carme; Girault, Jean-Antoine; Vila, Miquel; Angus, C. Nairn; Manso Sanz, Yasmina; Soriano Garcia, Eduardo
    In addition to neuronal migration, brain development, and adult plasticity, the extracellular matrix protein Reelin has been extensively implicated in human psychiatric disorders such as schizophrenia, bipolar disorder, and autism spectrum disorder. Moreover, heterozygous reeler mice exhibit features reminiscent of these disorders, while overexpression of Reelin protects against its manifestation. However, how Reelin influences the structure and circuits of the striatal complex, a key region for the above-mentioned disorders, is far from being understood, especially when altered Reelin expression levels are found at adult stages. In the present study, we took advantage of complementary conditional gain- and loss-of-function mouse models to investigate how Reelin levels may modify adult brain striatal structure and neuronal composition. Using immunohistochemical techniques, we determined that Reelin does not seem to influence the striatal patch and matrix organization (studied by μ-opioid receptor immunohistochemistry) nor the density of medium spiny neurons (MSNs, studied with DARPP-32). We show that overexpression of Reelin leads to increased numbers of striatal parvalbumin- and cholinergic-interneurons, and to a slight increase in tyrosine hydroxylase-positive projections. We conclude that increased Reelin levels might modulate the numbers of striatal interneurons and the density of the nigrostriatal dopaminergic projections, suggesting that these changes may be involved in the protection of Reelin against neuropsychiatric disorders.