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

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Biofilm formation of Tenacibaculum maritimum, a fish pathogenic bacteria, to evaluate the antimicrobial activity of fish skin mucus
(Frontiers Media, 2025-10-13) Tejero, Marc; Sanahuja Piera, Ignasi; Balsalobre Parra, Carlos; Ibarz i Valls, Antoni; Madrid Xufré, Cristina; Fernández-Alacid, Laura
Biofilms, defined as aggregates of microorganisms embedded in a self-produced matrix of extracellular polymeric substances (EPS), are formed by most bacteria in both natural and pathogenic ecosystems. In aquaculture, biofilms pose a dual challenge: they confer recalcitrance to antimicrobials treatments and contribute to persistent infections by forming on facility surfaces such as tanks, nets, cages, and equipment. Tenacibaculum maritimum, the causative agent of tenacibaculosis, is responsible for significant economic losses in fish farming. Although the antibacterial activity of fish skin mucus against this pathogen has been evaluated in vitro, its effects on T. maritimum biofilms have not yet been determined. In this study, we provide a simple methodology for the in vitro formation and quantification of T. maritimum biofilms to monitor antibacterial properties of different compounds or substances, such as fish skin mucus. For this purpose, biofilm formation was assessed under varying culture volumes (200, 300, and 400 µL) and incubation times (24, 48, and 72 hours) in 48-well microplates. Then, the effects of gilthead seabream (Sparus aurata) skin mucus were evaluated on planktonic growth, biofilm formation, and biofilm dispersion, measuring both biomass and metabolic activity. Based on the tested volumes and incubation times, the optimal condition for biofilm formation was defined as 24 hours in MB at 25 ºC using 200 µL culture volume. These conditions supported the development of a biofilm (OD570>1.5 after crystal violet staining) while conserving time and mucus. Seabream mucus significantly impaired T. maritimum planktonic growth and biofilm formation in a concentration-dependent manner. Non-diluted mucus completely inhibited planktonic growth and biofilm metabolic activity, and reduced biofilm biomass by 81.16 ± 2.54%. In contrast, its effect on mature biofilms was limited, with reductions of approximately 50% in metabolic activity and 40% in biomass. This study provides a platform to assess how different fish culture conditions affect the host’s susceptibility to T. maritimum infections, which is crucial for preventing economic losses in fish farming. Additionally, it opens the door to studies analyzing the components of fish skin mucus responsible for its antibacterial activity, aiming to develop novel therapeutic compounds for targeting biofilms formed by this pathogen.
Endogenous LXR signaling controls pulmonary surfactant homeostasis and prevents lung inflammation
(Springer Verlag, 2024-07-06) Hernández-Hernández, Irene; Rosa, Juan V. de la; Martín-Rodríguez, Patricia; Díaz-Sarmiento, Mercedes; Recio, Carlota; Guerra, Borja; Fernández-Pérez, Leandro; León Moreno, Theresa Elizabeth; Torres, Rosa; Font Díaz, Joan; Roig, Angela; Mora, Fernando de; Boscá, Lisardo; Díaz, Mario; Valledor Fernández, Annabel; Castrillo, Antonio; Tabraue, Carlos
Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRβ, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRβ as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases.
Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
(Karger, 2024-12-19) Glaría Percaz, Estibaliz; Rodríguez Martínez, Pol; Font Díaz, Joan; Rosa, Juan Vladimir de la; Castrillo, Antonio; Crawshaw, Dylan J.; Vidal Taboada, José Manuel; Saura Martí, Josep; Matalonga, Jonathan; Nunes Chini, Eduardo; Caelles Franch, Carme; Valledor Fernández, Annabel
Introduction: Macrophages abundantly express liver X receptors (LXRs), which are ligand-dependent transcription factors and sensors of several cholesterol metabolites. In response to agonists, LXRs promote the expression of key lipid homeostasis regulators. Cross talk between LXRs and inflammatory signals exists in a cell type- and gene-specific manner. A common feature in the macrophage response to inflammatory mediators is the induction of CCAAT/enhancer-binding protein beta (C/EBPβ), a master transcriptional regulator and lineage-determining transcription factor in monocytes/macrophages. Methods: Quantitative real-time PCR in control and C/EBPβ-deficient macrophages was used to explore the role of C/EBPβ in the cross talk between inflammatory mediators and the macrophage response to pharmacological LXR activation. The functional interaction between C/EBPβ and LXRs on selected genomic regions was further characterized by chromatin-immunoprecipitation (ChIP) and gene reporter studies. Results: Whereas inflammatory signaling repressed several LXR-regulated genes involved in lipid metabolism, these effects were conserved after deletion of C/EBPβ. In contrast, inflammatory mediators and LXRs synergistically induced the expression of the multifunctional protein CD38 in a C/EBPβ-dependent manner. C/EBPβ and LXRs bound to several regions with enhancer activity upstream and within the mouse Cd38 gene and their functional cooperation in macrophages required intact binding sites for LXR and C/EBPβ. Conclusion: This study reveals positive cross talk between C/EBPβ and LXRs during the macrophage inflammatory response, which selectively impacts CD38 expression.
Identification of Neuritin 1 as a local metabolic regulator of brown adipose tissue
(Nature Publishing Group, 2025-09-04) Sánchez Feutrie, Manuela; Romero De Pablos, Montserrat; Veiga, Sonia Rosa Pereira da; Borràs Ferré, Núria; Berrow, Nick; Ràfols, Martina; Giménez, Noemí; Rodgers Furones, Andrea; Sabaté Pérez, Alba; Rodríguez Pérez, Ángela; Cataldo, Luis Rodrigo; Burghardt, Hans; Sebastián, David; Plana, Natàlia; Hernández, Vanessa; Alcaide, Laura Isabel; Reina, Óscar; Monte, M. Jesús; García Marin, José Juan; Palacín Prieto, Manuel; Burcelin, Remy; Antonson, Per; Gustafsson, Jan-Ake; Zorzano Olarte, Antonio
Brown adipose tissue (BAT) plays a key role in metabolic homeostasis through its thermogenic effects and the secretion of regulatory molecules. Here we report that RAP250 haploinsufficiency stimulates BAT in mice, thus contributing to a decrease in fat accumulation. Local in vivo AAV-mediated RAP250 silencing in BAT reduces body weight and fat mass and enhances glucose oxidation, thereby indicating that RAP250 participates in the regulation of BAT metabolic activity. Analysis of the mechanisms led to the finding that Neuritin 1 is produced and released by brown adipocytes, it plays a key metabolic role, and it participates in the enhanced BAT metabolic activity under RAP250 deficiency. Forced overexpression of Neuritin 1 in UCP1-expressing cells markedly decreases fat mass and body weight gain in mice and induces the expression of thermogenic genes in BAT. Neuritin 1-deficient brown adipocytes also shows a reduced β-adrenergic response. We demonstrate a metabolic role of BAT-derived Neuritin 1 acting through an autocrine/paracrine mechanism. Based on our results, Neuritin-1 emerges as a potential target for the treatment of metabolic disorders.
Lung diffusing capacity after different modalities of exercise at sea level and hypobaric simulated altitude of 4000 m
(2023-09-30) García Alday, Iker; Drobnic, Franchek; Arrillaga, Beatriz; Cheng, Yinkiria; Javierre Garcés, Casimiro F.; Pons, Vicente; Viscor Carrasco, Ginés
Introduction: Lung diffusion capacity of carbon monoxide (DLCO) provides a measure of gas transfer in the lungs, which increase in relation to exercise and decrease in the presence of lung interstitial disease. The aim of this study is to evaluate the changes in lung diffusion after anaerobic and aerobic exercise in a cycle ergometer. Material and method: The participants were 11 healthy active subjects, including 8 females and 3 males (age: 24.3 ± 3.1 years). Lung diffusion capacity for carbon monoxide (DLCO) was studied under two different protocols: In the first day, DLCO was measured at SL at rest (SL-R), after 30-s maximal exercise (SL-ANA), and after 15-min moderate continuous exercise (SL-AER). In the second day, DLCO was evaluated at rest at SL, and then at HA (4,000 m) at rest (HA-R) and after 30-min of moderate interval exercise (HA-AER). Results: There was an increase in DLCO from rest to after SL-ANA (32.5 ± 6.4 to 40.3 ± 11.6 mL·min-1·mmHg-1, P = 0.027). In the second day, DLCO was evaluated at rest at SL, and then at HA (4,000 m) at rest (HA-R) and after 30-min of moderate interval exercise (HA-AER). During HA exposure, there was no changes in DLCO, either at HA-R, or after HA-AER. Conclusions: Lung diffusion capacity largely increased after 30-s maximal exercise in a cycle ergometer, although the O2 -dependence is small during this type of anaerobic exercise. Thus, exercise intensity may be a key modulator of the changes in lung diffusing capacity in relation to exercise.
Modulation of digestive enzyme activities and intestinal γ-Proteobacteria in gilthead sea bream fed high-fat diets supplemented with HIDROX olive oil extract
(MDPI, 2025-07-16) García Meilán, Irene; Balbuena-Pecino, Sara; Montblach, Manel; Ramos Romero, Sara; Fontanillas, Ramon; Gutiérrez Fruitós, Joaquín; Capilla Campos, Encarnación; Navarro Álvarez, Isabel; Gallardo Romero, María Ángeles
High-fat diets are commonly used in fish farming due to their protein-sparing effect, contributing to reduced production costs. However, this practice may have adverse effects such as metabolic impairment and inflammation. These problems can be assessed in two ways: by developing functional diets or using food restriction, which leads to compensatory growth. The present study characterized digestion in gilthead sea bream fed a high-fat diet in the presence (HT) or absence (HF) of an olive oil polyphenol as an additive, hydroxytyrosol, under two different dietary regimes: feeding to satiation (ST) or at a 40% restriction (R). Digestive enzyme activities, specifically trypsin-like activities, were mainly upregulated by dietary treatment (HT). In contrast, restriction effects mainly appeared during digestion in the pyloric caeca, where a significant rise in chymotrypsin-like activities was detected. Moreover, those fish tended to have an increased relative intestinal length compared to those fish fed at a standard ration. Feed restriction enhanced the growth of γ-Proteobacteria in pyloric caeca and proximal intestinal regions, without altering their population in the distal intestine. Overall, it is suggested that hydroxytyrosol inclusion at a standard ration could improve digestion processes in gilthead sea bream fed high-fat diets under healthier conditions than without this additive.
Patient Stratification for Serum LDH Levels Reveals Distinct CLA+ T-Cell Cytokine Secretion in Response to HDM, Clinical Features and Allergic Comorbidities
(MDPI, 2025-08-13) García Jiménez, Irene; Figueras Nart, Ignasi; Sans de San Nicolás, Lídia; Curto Barredo, Laia; Bertolín Colilla, Marta; Bonfill Ortí, Montserrat; Díez Ribas, Sandra; Llobet del Pino, Alex; Guilabert Vidal, Antonio; Ryzhkova, Anna; Ferran, Marta; Pujol, Ramon M.; Santamaria Babí, Luis F.
Lactate dehydrogenase (LDH) is a serum biomarker well known to correlate with disease severity in atopic dermatitis (AD). The aim of this study was to explore the cutaneous immune responses and the clinical profile of AD patients in relation to serum LDH levels. To this end, 47 untreated, adult patients with moderate-to-severe AD were stratified by median levels of serum LDH. Circulating memory T-cell responses to house dust mite (HDM) extract, in the presence of autologous lesional epidermal cells, were compared between AD subgroups. The LDHhigh group exhibited significantly higher IL-13, IL-5 and IL-9 in vitro responses confined to the cutaneous lymphocyte-associated antigen (CLA)+ subset compared to LDHlow patients. Clinically, LDHhigh patients were younger and exhibited more severe disease, elevated eosinophil counts in their blood, increased total and specific IgE levels in their plasma, and a higher prevalence of allergic rhinitis. Our data suggests that high LDH levels identify a subgroup of AD patients with a specific immune and clinical profile, and highlight the potential of LDH as a clinical parameter that may enable patient stratification for treatment selection.
Combined effects of Pediococcus acidi lactici and natuzyme on growth performance, hematology and immunity indices in juvenile beluga (Huso huso)
(Elsevier B.V., 2022-06-01) Musavi, Maryam; Hasanpour, Shaghayegh; Safari, Roghieh; Imanpoor, Mohammad Reza; Gutiérrez Fruitós, Joaquín
The present study was performed to compare the combined and individual effects of Pediococcus acidi lactici (PB) and natuzyme (a cocktail of protease, lipase as well as non-starch polysaccharidases) on the immune response and growth performance parameters of the juvenile beluga (Huso huso). To prepare the treatment diets, the basal diet was supplemented with either the exogenous natuzyme (at 0, 0.25 and 0.5 g kg(-1)), PB (at 0% and 0.1%) or both of them. The six treatments were assigned to triplicate groups and the feeding trial lasted for two months. The results showed that PB treatment constrained the positive effect of EN (especially at the higher dose) on the FCR and final weight. However, IGF and GH expression not only increased following either PB or EN inclusion, but also, their simultaneous addition promoted their individual effects. Together, higher level of GH and IGF mRNA levels in this study was not associated with a significant growth enhancement, this can be due to the fact that more time should be considered to display their effects. In the light of these results, we recommend that the combined use of probiotics and exogenous enzymes especially at the higher dose can be inhibitory.
CLA+ memory T cells in atopic dermatitis CLA plus T cells and atopic dermatitis
(John Wiley & Sons, 2023-07-13) Sans de San Nicolàs, Lídia; Czarnowicki, Tali; Akdis, Mubeccel; Pujol, Ramon M.; Lozano-Ojalvo, Daniel; Leung, Donald Y. M.; Guttman-Yassky, Emma; Santamaria Babí, Luis F.
Circulating skin-homing cutaneous lymphocyte-associated antigen (CLA)+ T cells constitute a small subset of human memory T cells involved in several aspects of atopic dermatitis: Staphylococcus aureus related mechanisms, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL-13, IL-31, pruritus, CCL17 and early effects on dupilumab-treated patients have in common that they are associated with the CLA+ T cell mechanisms in atopic dermatitis patients. The function of CLA+ T cells corresponds with the role of T cells belonging to the skin-associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis and many other T cell mediated skin diseases. The goal of this review is to gather all this translational information of atopic dermatitis pathology.
AIM/CD5L: A Key protein in the control of immune homeostasis and inflammatory disease
(Oxford University Press, 2015-06-05) Sanjurjo, Lucía; Aran, Gemma; Roher, Nerea; Valledor Fernandez, Annabel; Sarrias, Maria Rosa
CD5L, a soluble protein belonging to the scavenger receptor cysteine-rich superfamily, is expressed mostly by macrophages in both lymphoid and inflamed tissues. The expression of this protein is transcriptionally controlled by liver X receptors, members of the nuclear receptor family that play major roles in lipid homeostasis. Research undertaken over the last decade has uncovered critical roles of CD5L as a pattern recognition receptor of bacterial and fungal components and in the control of key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In this review, we summarize the current knowledge of CD5L, its roles at the intersection between lipid homeostasis and immune response, and its potential use as a diagnostic biomarker in a variety of diseases, such as tuberculosis and liver cirrhosis.
Physical Activity and Pain Perception in Residents Under Conditions of Chronic Hypoxia
(MDPI, 2025-06-30) Bernedo Itusaca, Margot Evelin; Vilca-Coaquira, Kely Melina; Calisaya-Huacasi, Ángel Gabriel; Cosi Cupi, Madeleyne Rosmery; Leqque Santi, Stanley Rivaldo; Cutipa Tinta, Shantal; Salazar Granara, Alberto; Pino Vanegas, Yoni Martín; Flores Paredes, Alcides; Guo, Shihui; Li, William; Yang, Mingming; Viscor Carrasco, Ginés; Hancco Zirena, Ivan
(1) Background: Previous studies indicate that individuals who engage in regular physical activity have a higher pain threshold than those who do not exercise. However, it remains unclear how this phenomenon behaves in individuals exposed to chronic hypoxia. This study evaluates pain perception at high altitude between high-altitude natives who exercised regularly and those who did not practice physical activity. (2) Methods: Eighty-four healthy volunteers aged 20 to 30 years old with a body mass index (BMI) within the normal range (18.5–24.9) residing in the city of Puno (3825 m) were recruited. The unilateral ischemia pain provocation test was used, applying pressure with a manual sphygmomanometer to generate transient ischemia in the arm while the patient opens and closes their hand. Onset, peak, and resolution times of pain, heart rate, and oxygen saturation were recorded. (3) Results: The average time to pain onset in the right arm was 30.2 s ± 14.1 during light physical activity, whereas, during moderate physical activity, it increased to 32.5 s ± 15.4. In the left arm, the average time until pain sensation was 27.9 s ± 16.8 during light physical activity and increased to 34.6 s ± 18.5 with moderate physical activity. Regarding the progression of pain intensity, the average time to reach unbearable pain in the right arm was 54.1 s ± 16.4 during light physical activity and 53.8 s ± 19.6 during moderate physical activity; in the left arm, it was 53.0 s ± 19.6 during light physical activity, increasing to 59.3 s ± 24.5 during moderate physical activity. (4) Conclusions: A more stable and slightly higher pain tolerance in the dominant arm was observed.
Trophic role and predatory interactions between the blue crab Callinectes sapidus and native species in open waters of the Ebro Delta
(Elsevier Ltd., 2024-01-29) Prado Villegas, Patricia; Baeta Alacio, Marc; Mestre, Estel; Solís, Marco Antonio; Sanahuja Piera, Ignasi; Gairín, Ignasi; Camps Castellà, Judith; Falco, Silvia; Ballesteros, Manuel (Ballesteros Vázquez)
The Ebro Delta has become a major blue crab (Callinectes sapidus) fishery area in the NW Mediterranean, but there is limited information on factors controlling the abundance of populations in open waters, a crucial habitat for ovigerous females. Here, we use a stable isotope approach (δ15N and δ13C), to assess blue crab trophic position, the potential consumption of food items using mixing models, and the isotopic niche overlap with local commercial species. For Octopus vulgaris, a potential blue crab key predator, a trophic enrichment experiment was also conducted to further assess predation control in wild populations. The blue crab showed 1.6 times higher trophic position than in other habitats of the Ebro Delta, and similar to that found in the harbor crab, Liocarcinus depurator, and several predatory fish. Additionally, the isotopic niche of blue crabs showed overlaps from 46.2 to 14.9% with native predators, and mixing models also suggest even dietary contributions throughout the food web. For O. vulgaris, field results showed a trophic position of 3.93, lower than that of blue crab, and lower δ15N signatures were also obtained in a captivity experiment drawing negative fractionation (−1.1‰). We conclude that high dietary contribution of animal prey might provide a high protein diet that could be crucial for allowing the maintenance of a large local population, but the overall functional trophic similarity could also disfavor local native species. The similarity between experimental fractionation and field differences between predator and prey (−1.6‰) suggests that predation of blue crab is possible, but further research is needed to clarify the metabolic routes involved in octopus δ15N fractionation.
Unlocking the full potential of human pluripotent stem cell–derived kidney organoids through bioengineering
(Elsevier, 2025-04-24) Goux Corredera, Iphigénie; Amato, Gaia; Moya Rull, Daniel; Garreta Bahima, Elena; Montserrat Pulido, Núria
Human pluripotent stem cells hold inherent properties, allowing researchers to recapitulate key morphogenetic processes. These characteristics, coupled with bioengineering techniques, have led to the definition of early procedures to derive organ-like cell cultures, the so-called organoids. With regard to kidney organoids, challenges stand ahead, such as the need to enhance cellular composition, maturation, and function to that found in the native organ. To this end, the kidney organoid field has begun to nourish from innovative engineering approaches aiming to gain control on the externally imposed biochemical and biophysical cues. In this review, we first introduce how previous research in kidney development and human pluripotent stem cells has informed the establishment of current kidney organoid procedures. We then discuss recent engineering approaches to guide kidney organoid self-organization, differentiation, and maturation. In addition, we present current strategies to engineer vascularization and promote in vivo–like physiological microenvironments as potential solutions to increase kidney organoid lifespan and functionality. We finally emphasize how working at the cusp of cell mechanics and computational biology will set the ground for successful translational applications of kidney organoids.
PVR–CD226 interaction regulates IL-10 production during human T cell differentiation
(BMJ Publishing Group, 2025-04) Lozano Garcia, Ester; Mena, Mari-Pau; Díaz Sánchez, Tania; Rosiñol Dachs, Laura
Presence of plate-bound PVR or nectin-2 at 2 µg/mL did not significantly modify cell viability nor frequency of proliferating cells compared to isotype control. As expected, Treg conditions significantly increased FoxP3 expression (paired T test p<0.0001, n=6) which was accompanied by elevation of CD226 levels (p=0.0026). Surprisingly, Treg conditions led to reduction of TIGIT expression (p=0.0039) and CD96 (p=0.084). In addition, PVR ligation resulted in a higher frequency of IL10-producing cells in Th0 conditions (p=0.0193), most of them expressing high levels of CD226 (78.48% ± 2.324), CD96 (59.87% ± 4.032), and to a lesser extent, TIGIT (39.82% ± 4.043). Consistently, under these experimental conditions dual blockade of TIGIT and CD96 did not abrogate the increase in the percentage of IL-10 producing cells, suggesting that PVR binds CD226 expressing cells to upregulate IL-10 production.
Effects of intermittent pneumatic compression on the recovery of cardiovascular parameters after repeated sprint exercise
(Springer Verlag, 2024-04) Artés, Arnau; Ferrer-Ramos, Pau; Javierre Garcés, Casimiro F.; Viscor Carrasco, Ginés; García Alday, Iker
Purpose: Intermittent pneumatic compression (IPC) applies gradual pressure to facilitate lymph and blood flow movement to reduce exercise-induced tissue fluid accumulation and plasma volume loss. This study aimed to evaluate the cardiovascular system response during the recovery with IPC compared with passive recovery (Sham). Methods: Sixteen volunteers (7 females and 9 males) executed a cycling-based exhausting sprint interval exercise (8 × 20 s all out), followed by a 30-min IPC or Sham condition. Participants performed two trials in a randomised, counterbalanced, and crossover design. Several cardiovascular parameters (blood pressure, heart function, and peripheral vascular resistance) were recorded at baseline (5ʹ), through the recovery protocol (30ʹ), and afterwards (5ʹ). Results: The use of IPC during the recovery phase led to a faster recovery, stated in relative values to pre-exercise, in mean blood pressure (102.5 ± 19.3% vs. 92.7 ± 12.5%; P < 0.001), and cardiac output (139.8 ± 30.0% vs. 146.2 ± 40.2%; P < 0.05) in comparison to Sham condition. Furthermore, during the IPC-based recovery, there was a slower recovery in cardiac pressure change over time (92.5 ± 25.8% vs. 100.5 ± 48.9%; P < 0.05), and a faster return to pre-exercise values in the peripheral vascular resistance (75.2 ± 25.5% vs. 64.8 ± 17.4%; P < 0.001) compared to Sham. Conclusion: The application of IPC after high-intensity exercise promotes the recovery of the cardiovascular system, reducing cardiovascular strain. Future investigations should consider the effects on the sympathetic-parasympathetic balance, such as heart rate variability, to assess further bonds between the use of IPC and autonomous control.
Covariant Formulation of the Brain’s Emerging Ohm’s Law
(MDPI, 2024-12) Rivas, Manuel; Reina del Pozo, Manuel
It is essential to establish the validity of Ohm’s law in any reference frame if we aim to implement a relativistic approach to brain dynamics based on a Lorentz covariant microscopic response relation. Here, we obtain a covariant formulation of Ohm’s law for an electromagnetic field tensor of any order derived from the emergent conductivity tensor in highly non-isotropic systems, employing the bidomain theory framework within brain tissue cells. With this, we offer a different perspective that we hope will lead to understanding the close relationship between brain dynamics and a seemingly ordinary yet profoundly crucial element: space.
LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy
(Nature Publishing Group, 2019-06-11) Pascual-García, Mónica; Bonfill-Teixidor, Ester; Planas-Rigol, Ester; Rubio-Perez, Carlota; Iurlaro, Raffaella; Arias, Alexandra; Cuartas, Isabel; Sala-Hojman, Ada; Escudero, Laura; Martínez-Ricarte, Francisco; Huber-Ruano, Isabel; Nuciforo, Paolo; Pedrosa, Leire; Marques, Carolina; Braña, Irene; Garralda, Elena; Vieito, María; Squatrito, Massimo; Pineda, Estela; Graus Ribas, Francesc; Espejo, Carmen; Sahuquillo, Juan; Tabernero Caturla, Josep; Seoane Suárez, Joan
Cancer response to immunotherapy depends on the infiltration of CD8⁺ T cells and the presence of tumor-associated macrophages within tumors. Still, little is known about the determinants of these factors. We show that LIF assumes a crucial role in the regulation of CD8⁺ T cell tumor infiltration, while promoting the presence of protumoral tumor-associated macrophages. We observe that the blockade of LIF in tumors expressing high levels of LIF decreases CD206, CD163 and CCL2 and induces CXCL9 expression in tumor-associated macrophages. The blockade of LIF releases the epigenetic silencing of CXCL9 triggering CD8⁺ T cell tumor infiltration. The combination of LIF neutralizing antibodies with the inhibition of the PD1 immune checkpoint promotes tumor regression, immunological memory and an increase in overall survival.
Effects of rapid gravity load changes on immunophenotyping and leukocyte function of human peripheral blood after parabolic flight
(Elsevier Ltd., 2023-09) Gorgori-González, Abril; Pérez Poch, Antoni; González, Daniel V.; Salvia, Roser; G. Rico, Laura; Ward, Michael D.; Bradford, Jolene A.; Pétriz González, Jordi; Viscor Carrasco, Ginés
One of the biological systems that suffers a physiological de-conditioning in space is the immune system. It is in charge of defending the body against pathogens and other aggressions. The aim of this work is to assess if there are any relevant changes in the aggregation of erythrocytes, cell count, immunophenotyping and functionality after parabolic flight. This effect has been assessed ex vivo using human peripheral blood, which was drawn from the radial vein (n=6 healthy volunteers) and anticoagulated with heparin and EDTA. Blood samples were split into two aliquots and maintained in two identical thermally isolated boxes; one stayed on the ground whereas the other one was subjected to parabolic flight. The parabolic flight consisted of 15 parabolas performed with a Mudry CAP-10B acrobatic aircraft. Each parabola consists of 8 seconds of hypogravity preceded and followed by 2 seconds of hypergravity. Any of the biological parameters measured showed no statistically significant differences. Altered gravity could increase aggregation of red blood cells, as demonstrated by a decrease in the number of single cells after parabolic flight exposure. No counting changes in haemoglobin concentration were observed when comparing the two different groups. Furthermore, potential functional alterations of monocytes and neutrophils cannot be rejected. Although these possible changes could be associated with hypogravity, other factors such as hypergravity and acceleration or deceleration cannot be ruled out. Our findings indicate that, under this specific experimental setup, there was no significant alteration in leukocyte Revised Manuscript (Clean version) Click here to view linked References immunophenotyping and functional capacity when using ex vivo blood samples and short exposure to altered gravity.
Deletion of Wt1 during early gonadogenesis leads to differences of sex development in male and female adult mice
(Public Library of Science (PLoS), 2022-06-15) Torres-Cano, Alejo; Portella-Fortuny, Rosa; Müller Sánchez, Claudia Alejandra; Porras-Marfil, Sonia; Ramiro-Pareta, Marina; Chau, You-Ying; Reina del Pozo, Manuel; Soriano Zaragoza, Francesc X. (Francesc Xavier); Martínez Estrada, Ofelia María
Assessing the role of the WT1 transcription factor (WT1) during early gonad differentiation and its impact on adult sex development has been difficult due to the complete gonadal agenesis and embryonic lethality exhibited by Wt1KO mouse models. Here, we generated Wt1LoxP/GFP;Wt1Cre mice, the first Wt1KO mouse model that reaches adulthood with a dramatically reduced Wt1 expression during early gonadogenesis. Wt1LoxP/GFP;Wt1Cre mice lacked mature gonads and displayed genital tracts containing both male and female genital structures and ambiguous genitalia. We found that WT1 is necessary for the activation of both male and female sex-determining pathways, as embryonic mutant gonads failed to upregulate the expression of the genes specific for each genetic programme. The gonads of Wt1LoxP/GFP;Wt1Cre mice showed a lack of production of Sertoli and pre-granulosa cells and a reduced number of germ cells. NR5A1 and the steroidogenic genes expression was modulated differently in XY and XX Wt1LoxP/GFP;Wt1Cre gonads, explaining the mutant phenotypes. Further studies of the XX Wt1LoxP/GFP;Wt1Cre gonads revealed that deletion of WT1 at an early stage impaired the differentiation of several cell types including somatic cells and the ovarian epithelium. Through the characterisation of this Wt1KO mouse model, we show that the deletion of Wt1 during early gonadogenesis produces dramatic defects in adult sex development.
JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
(BioMed Central, 2022-12-01) Busquets Figueras, Oriol; Espinosa-Jiménez, Triana; Ettcheto Arriola, Miren; Olloquequi, Jordi; Bulló, Mònica; Carro, Eva; Cantero, Jose L.; Casadesús, Gemma; Folch, Jaume; Verdaguer Cardona, Ester; Auladell i Costa, M. Carme; Camins Espuny, Antoni
Background and aim The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements. Methods Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice at 9 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-GTT and IP‑ITT) were performed to evaluate peripheral biometrics. Additionally, cognitive behavioral tests and analysis of spine density were performed to assess cognitive function. Molecular studies were carried out to confirm the effects of metabolic stressors in the hippocampus relative to cognitive loss. Results Our studies demonstrated that HFD in Jnk3−/− lead to synergetic responses. Loss of function of JNK3 led to increased body weight, especially when exposed to an HFD and they had significantly decreased response to insulin. These mice also showed increased stress in the endoplasmic reticulum and diminished cognitive capacity. However, loss of function of JNK1 promoted normal or heightened energetic metabolism and preserved cognitive function even when chronically metabolically stressed. Conclusions Downregulation of JNK3 does not seem to be a suitable target for the modulation of energetic-cognitive dysregulations while loss of function of JNK1 seems to promote a good metabolic-cognitive profile, just like resistance to the negative effects of chronic feeding with HFD.

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