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Articles publicats en revistes (Bioquímica i Fisiologia)

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    Maternal Extra Virgin Olive Oil Supplementation Enhances Offspring Immune Function: A Preclinical Study
    (MDPI, 2025-08) Zhan-Dai, Sonia; Grases Pintó, Blanca; García-Vara, Adriana; Ferrer i Roig, Ruth; Martín Venegas, Raquel; Lamuela Raventós, Rosa Ma.; Castell, Margarida; Pérez-Cano, Francisco J.; Vallverdú i Queralt, Anna; Rodríguez Lagunas, María José
    Maternal diet influences offspring development, immune function, and intestinal health. This study investigates the effects of maternal supplementation with a key component of the Mediterranean Diet, extra virgin olive oil (EVOO), on the immune health of offspring at the end of lactation. Lewis rat dams received either refined olive oil (ROO), EVOO, or water (REF) during gestation and lactation. Plasma immunoglobulin G2c (IgG2c) concentration was elevated in pups born to EVOO-supplemented mothers, indicating enhanced immune development. Histological analysis of the small intestine revealed more goblet cells in the EVOO group, indicating a potential positive effect on the intestinal barrier function. In vitro assays showed that EVOO metabolites did not display cytotoxicity and had improved barrier integrity under a stress stimulus. These findings suggest that maternal EVOO supplementation may have beneficial effects on immune and intestinal development and health in offspring.
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    Greater fragmentation of the daily rhythm of energy intake is associated with better insulin sensitivity in rotating shift workers
    (Informa Healthcare, 2026-05-15) Pereira Marot, L.uisa; Zerón-Rugerio, María Fernanda; Cambras Riu, Trinitat; Tibiletti Balieiro, Laura Cristina; Rosa, Dayane Eusenia; Vale Cardoso Lopes, Tássia Do; Castro Moreno, Claudia Roberta de; Izquierdo Pulido, Maria; Crispim, Cibele Aparecida
    Shift workers are essential to sustaining the modern 24 h society. However, they experience a higher risk of developing metabolic syndrome, a vulnerability thought to arise from recurrent misalignment between their sleep-wake and fasting-eating schedules. This study aimed to investigate the association between the daily rhythms of energy and macronutrient intake, motor activity (MA), and wrist temperature (WT) with anthropometric and biochemical parameters in rotating shift workers (RSW). Thirty male RSW participated in this 10 d cross-sectional study. Anthropometric and biochemical measurements were collected, and a 10 d 24 h food recall was used to assess energy and macronutrient intake. From these data, daily rhythms of energy intake were characterized, and actigraphy was used to evaluate daily rhythms of MA and WT. Daily rhythms were analyzed using non-parametric analyses including the intradaily variability (IV) and interdaily stability (IS), and associations with outcome variables were tested using partial correlations. A negative association was observed between the IV of the daily rhythms of energy and carbohydrate intake with insulin levels (p < 0.05), HOMA-IR (p < 0.05), and triglycerides (p < 0.05). In contrast, higher IV in the daily rhythm of WT was associated with higher total cholesterol (p < 0.05) and LDL-cholesterol (p < 0.05). These results suggest that a higher fragmentation (higher IV) of the daily rhythm of energy intake is associated with better glucose tolerance among RSW.
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    Extracellular Vesicles from Escherichia coli Strains of the Gut Microbiota Trigger Hepatic Antioxidant and Anti-Lipogenic Effects via the Gut-Liver Axis in Healthy Neonatal Rats
    (MDPI, 2025-09-25) Martínez-Ruiz, Sergio; Badía Palacín, Josefa; Baldomà Llavinés, Laura
    Background: The gut-liver axis is essential for maintaining liver physiology, with the gut microbiota playing a central role in this bidirectional communication. Recent studies have identified microbiota-derived extracellular vesicles (EVs) as key mediators of inter-organ signaling. This study explored the impact of EVs from two beneficial Escherichia coli strains, the probiotic EcN and the commensal EcoR12, on hepatic metabolism and oxidative stress in healthy neonatal rats. Methods: EVs were administered orally during the first 16 days of life, and blood and liver samples were collected on days 8 and 16. Results: The results demonstrated that EVs significantly reduced intestinal permeability, as evidenced by decreased plasma zonulin levels. In the liver, EVs enhanced redox homeostasis by downregulating CYP2E1 and upregulating key antioxidant genes (SOD1, CAT, GPX). Furthermore, the treatment shifted liver metabolism toward an anti-lipogenic profile by inducing fatty acid oxidation genes (PPARA, CPT1A) and suppressing genes involved in de novo lipogenesis (SREBP1C, ACC1, FASN, CNR1). Importantly, markers of hepatic inflammation remained unchanged, indicating the safety of the intervention. In vitro experiments using human HepG2 cells supported these findings, further validating the antioxidant and metabolic effects of the EVs. Conclusions: Our results underscore the role of microbiota-derived EVs as important mediators of hepatic metabolic programming in healthy individuals via the gut-l
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    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.
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    Changes in the mucosal immunity induced by diets enriched with cocoa and hesperidin in intensively trained and exhausted rats
    (Nature Publishing Group, 2025-10-21) Ruiz Iglesias, Patricia; Pérez-Cano, Francisco J.; Rodríguez Lagunas, María José; Castell, Margarida; Massot Cladera, Malen
    Mucosal immunity can be altered by exhausting exercise, while it may be enhanced by flavonoid-enriched diets. This study aimed both to ascertain the influence of exhausting exercise in rats on mucosal immunity, and to establish the effect of 10% cocoa-enriched diets, alone (C10) or together with 0.5% hesperidin (CH), on the alterations in the mucosal immune system caused by exhausting exercise. For 6 weeks, Lewis rats were fed either standard, C10, or CH diets while following an intensive exercise training program. The animal groups included sedentary, trained, or exhausted rats for each diet. Results showed no effect of exercise on intestinal permeability or the main lymphocyte subsets of mesenteric lymph nodes (MLNs), although a higher proportion of NK cells were observed after training. Exhaustion increased the proportion of CD62L + Th and Tc cells but did not modify the lymphocyte functions of MLNs. Diets enriched with cocoa prevented the increase in the proportion of NK cells in MLNs whereas increased the proportion of B, Tc, and Tγδ cells. Although exercise did not modify the immunoglobulin synthesis, cocoa diets resulted in a rise in the synthesis of IgG and a lower salivary IgA content. In conclusion, few mucosal changes were induced in the model of exercise performed in Lewis rats, thus cocoa diets could not demonstrate a preventive effect on these alterations. Nevertheless, cocoa-enriched diets enhanced some aspects of intestinal immunity.
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    Quatsome nanovesicles as antibacterial platform: Mechanistic insights into their activity against planktonic and biofilm Staphylococcus aureus
    (Elsevier B.V., 2026-06-26) Korber, Mariana; Gallardo-Moreno, Amparo M; Ferrer-Tasies, Lidia; Fernandez-Calderon, Maria Coronada; Pujol-Sole, Nuria; Tomsen-Melero, Judit; Guasch, Elba; Tamurejo-Alonso, Purificacion; Mitjans Arnal, Montserrat; Vinardell, Maria Pilar; Domingo-Tafalla, Beatriu; Giannotti, Marina Inés; Rancan, Fiorenza; Schaudinn, Christoph; Veciana, Jaume; Ratera, Imma; Roldan, Monica; González-Mira, Elisabet; Gonzalez-Martin, Maria Luisa; Ventosa, Nora
    The growing threat of antibiotic-resistant pathogens has intensified the demand for alternative antibacterial materials. Quatsomes-nanovesicles composed of cholesterol and quaternary ammonium surfactants (QAS)- emerge as promising candidates due to their intrinsic antimicrobial properties and tunable physicochemical characteristics. Here, we investigate the antibacterial activity of quatsomes incorporating QAS with either tetradecyl (C14) or hexadecyl (C16) alkyl chains against Staphylococcus aureus, a leading cause of hospital-acquired infections. Both quatsome types exhibited potent bactericidal activity in planktonic cultures, with C16containing formulations showing a 2.5-fold lower minimum bactericidal concentration than C14 counterparts. Confocal microscopy suggested a partial penetration of cationic quatsomes into the bacterial peptidoglycan layer, accompanied by significant increases in zeta-potential, suggesting strong electrostatic interactions without visible membrane disruption, as confirmed by scanning electron microscopy. Both formulations also demonstrated high efficacy against mature S. aureus biofilms, with no significant differences between alkyl chain lengths, indicating a mechanism primarily targeting the extracellular biofilm matrix. In addition, they showed a good antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). A preliminary safety assessment using reconstructed human epidermis (EpiskinTM) confirmed the non-irritant nature of both formulations. These findings highlight the potential of QAS-based quatsomes as effective and biocompatible nanocarriers for topical antibacterial applications, offering a promising platform for combating antibiotic-resistant infections in both planktonic and biofilm states.
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    Cannabidiol as a multifaceted therapeutic agent: mitigating Alzheimer's disease pathology and enhancing cognitive function
    (BioMed Central, 2025-12-01) Raïch, Iu; Lillo, Jaume; Rebassa, Joan-Biel; Griñán Ferré, Christian; Bellver Sanchis, Aina; Reyes Resina, Irene; Franco Fernández, Rafael; Pallàs i Llibería, Mercè, 1964-; Navarro Brugal, Gemma
    Background Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has garnered significant interest due to its non-psychoactive nature and diverse receptor interactions. Methods This study employs in vitro and in vivo methodologies to validate CBD's potential as a treatment for Alzheimer's disease (AD) by addressing key hallmarks of the condition and promoting neuroprotective effects on spatial memory. Results Our findings demonstrate CBD's ability to decrease pTau and Aβ aggregation and to mitigate their axonal transport between cortical and hippocampal neurons. Moreover, CBD treatment was shown to reduce neuroinflammation, as CBD was able to skew microglia towards a neuroprotective M2 phenotype while attenuating proinflammatory cytokine release in the 5xFAD AD mouse model. Notably, daily CBD injections (10 mg/Kg) for 28 days in 5xFAD mice resulted in significant improvements in both short- and long-term spatial memory. The study also reveals CBD's capacity to partially revert neurite formation loss induced by Aβ, Tau, and pTau proteins, suggesting a potential role in promoting neuronal plasticity. Additionally, CBD treatment led to a reduction in reactive oxygen species (ROS) formation and increased neuronal viability in the presence of AD-associated protein aggregates. Conclusions These multifaceted effects of CBD, ranging from molecular-level modulation to behavioral improvements, underscore its potential as a comprehensive therapeutic approach for AD. The findings not only support CBD's neuroprotective properties but also highlight its ability to target multiple pathological processes simultaneously, offering a promising avenue for future AD treatment strategies.
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    A diet rich in fibre and vegetable protein during gestation and lactation shapes maternal immunity, intestinal microbiota and lipid metabolism
    (Elsevier, 2025-07-01) Rio Aige, Karla; Selma-Royo, Marta; Massot Cladera, Malen; Everard, Amandine; Castell, Margarida; Rodríguez Lagunas, María José; Collado, Maria Carmen; Pérez-Cano, Francisco J.
    Background Establishing optimal maternal nutritional habits during pregnancy, breastfeeding, and early life is crucial for the health and welfare of both the mother and the child. However, research is lacking to understand the associated mechanisms linking maternal diet to health outcomes. The objective of this study was to assess the potential inf luence of two distinct diets, consumed during gestation and lactation, on the microbiota composition, immunity and lipid metabolism of Lewis dams. Methods Diet 1 (D1, Mediterranean diet-like) was characterized by a high fibre content, vegetable protein, and fish oil; whereas Diet 2 (D2, slightly Western diet-like) was enriched with animal protein and lard. Fecal samples were collected weekly throughout the nutritional intervention. Blood, tissue samples (adipose tissue, intestine, mammary gland, spleen and liver) and cecal content were collected from the mother at the end of lactation (day 21) to examine the effects on the epithelial barrier, lipid metabolism, microbiota composition and metabolites, as well as the mucosal immunity. Findings According to our findings, consumption of the D1 diet had a beneficial impact on the mothers compared to the D2 diet. D1 increased the intestinal surface area and enhanced the mucosal immunity, as evidenced by a rise in fecal immunoglobulin (Ig) A and Ig-coated bacteria levels, along with an increase in total IgG in the mesenteric lymph nodes, as well as elevated levels of T helper (Th)1-associated IgG2c isotype. Furthermore, D1 influenced the adiposity and exerted an anti-obesogenic effect on brown adipose tissue by up-regulating the expression of the genes Ucp-1, Cidea, Prdm16 and Gpr43. D1 also influenced the cecal microbiota composition, impacting its functions such as the production of short-chain fatty acids in the caecum. D1 reduced microbiota diversity by increasing beneficial taxa, such as Ruminococcaceae family and Turicibacter genus, among others. These genera showed correlations with the analysed immune and lipid metabolism parameters suggesting that microbiome modulation serves as a link between the observed systemic effects and the dietary intervention. Interpretation The study highlights that a diet rich in fibre, vegetable protein, and fish oil, consumed during gestation and lactation, enhances maternal health by improving intestinal function, mucosal immunity, and exerting antiobesogenic effects on lipid metabolism, likely mediated by modifications in the cecal microbiota composition and function.
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    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.
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    Plant-derived compounds, vitagens, vitagenes and mitochondrial function
    (Elsevier, 2022-03-01) Franco Fernández, Rafael; Navarro Brugal, Gemma; Martínez-Pinilla, Eva
    There is great interest in identifying natural products that can be approved as nutraceuticals. A good option is to induce transcription of vitagenes, which would lead to increased expression of proteins that provide the means to maintain homeostasis. In fact, the induction of vitagenes is considered relevant during aging, especially if aging is accompanied by neurodegenerative diseases. Care must be taken to avoid confusing vitagenes, which are genes, and vitagens, which are vitamin-like low-molecular weight compounds; both concepts are recalled here. Although mitochondria are key factors in several chronic diseases of the nervous system, the amount of vitagenes that is associated with better mitochondrial function (bioenergetics, oxidative stress, biogenesis, dynamics, etc.) is limited. Plant molecules have been used for centuries to improve well-being, and some have a directly or indirectly impact on mitochondrial function. However, there is little knowledge about whether plant-derived products can induce vitagenes related to the enhancement of the multiple actions exerted by mitochondria; studies are needed to detect natural plant compounds that increase the transcription of genes related to the function of this cellular organelle. This study is expected to identify new vitagenes whose induction provides benefits in aging and/or neurodegenerative diseases.
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    White adipose tissue dysfunction in obesity and aging
    (Elsevier B.V., 2021) Reyes-Bossio, Mario; Fos Domènech, Júlia; Serra i Cucurull, Dolors; Herrero Rodríguez, Laura; Sánchez-Infantes, David
    Both obesity and aging are associated with the development of metabolic diseases such as type 2 diabetes and cardiovascular disease. Chronic low-grade inflammation of adipose tissue is one of the mechanisms implicated in the progression of these diseases. Obesity and aging trigger adipose tissue alterations that ultimately lead to a pro-inflammatory phenotype of the adipose tissue-resident immune cells. Obesity and aging also share other features such as a higher visceral vs. subcutaneous adipose tissue ratio and a decreased lifespan. Here, we review the common characteristics of obesity and aging and the alterations in white adipose tissue and resident immune cells. We focus on the adipose tissue metabolic derangements in obesity and aging such as inflammation and adipose tissue remodeling.
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    Incidence and risk factors for calcification after dextranomer/hyaluronic acid (Dx/HA) copolymer injection for vesicoureteral reflux
    (Elsevier, 2021-06-01) Soria-Gondek, Andrea; Martín Solé, Oriol; Pérez Bertólez, Sonia; Martín Lluís, Alba; Tarrado Castellarnau, Xavier; García-Aparicio, Luis
    Introduction Since the first case of dextranomer/hyaluronic acid (Dx/HA) implant calcification in 2008, concern about the long-term sequelae of Dx/HA injection has been growing. According to previous reports, the incidence of Dx/HA calcification 4 years after injection would be around 2%. The risk and the incidence rate of Dx/HA implant calcification were higher than expected. The hazard of calcification was higher between 3 and 5 years after injection. The risk was especially higher in patients treated before the age of 3.5. Caution should be taken not to confuse implant calcifications with ureteric stones. A 5-year follow-up would set a better understanding of the actual incidence and clinical significance of implant calcification.
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    Cerebrospinal fluid sediments as a novel tool for potential biomarkers of neurodegenerative diseases
    (MDPI, 2026-04-21) Alsina Planelles, Raquel; Riba Baques, Marta; Sartorio Pach, Marina; Romera Niño, Clara; Vilaplana Pelegrí, Berta; Prats Miralles, Eva; Molina Porcel, Laura; Del Valle Macia, Jaume; Pelegrí, Carme; Vilaplana i Hortensi, Jordi
    Cerebrospinal fluid (CSF) biomarkers for neurodegenerative diseases have been extensively studied over the years. However, CSF samples are routinely centrifuged, and the resulting sediment or pellet is typically discarded to remove cellular debris and high-density particles. This standard practice raises a critical question: Could these discarded sediments harbour potential biomarkers? The aim of the present study is to demonstrate that CSF sediments contain specific brain-derived components and thus to substantiate the possible presence of biomarkers within these sediments. To this end, we analysed post-mortem CSF samples of one patient with neuropathologically confirmed Alzheimer’s disease (AD) and one patient with confirmed progressive supranuclear palsy (PSP). CSF pellets were studied using transmission and scanning electron microscopy techniques (TEM and SEM, respectively), along with compositional analysis through SEM combined with energy-dispersive X-ray spectroscopy (SEM-EDX), as well as immunofluorescence and histochemical analyses on semithin pellet sections. We observed that, among others, CSF pellets contain brain-derived structures such as wasteosomes and psammoma bodies. Furthermore, we also found disease-relevant proteins, including tau and Aβ42 in the AD sediment and tau in the PSP sediment. Although further studies are required, the study of CSF pellets could open new avenues for biomarker discovery in neurodegenerative diseases.
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    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.
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    Bifidobacterium breve M-16 V and scGOS/lcFOS Supplementation to Dams Ameliorates Infant Rotavirus Infection in Early Life
    (Wiley-VCH, 2024-10-29) Sáez Fuertes, Laura; Rio-Aige, Karla; Massot Cladera, Malen; Castell, Margarida; Knipping, K.; Garssen, J.; Bourdet-Sicard, Raphaëlle; Rodríguez Lagunas, María José; Collado, Maria Carmen; Pérez-Cano, Francisco J.
    The immune system of newborns is underdeveloped, leaving them susceptible to infections like rotavirus (RV). Despite vaccines, RV remains a leading cause of child mortality, especially in developing countries. Maternal immunity is transferred during pregnancy and breastfeeding to the offspring providing protection against RV infection. This study aims to explore how the maternal diet can enhance the newborn’s ability to fight early infections. Pregnant rats received orally Bifidobacterium breve M-16 V and short chain galacto-oligosaccharides (scGOS)/long chain fructo-oligosaccharides (lcFOS). At day 5 of life pups are infected with RV and at day 8, samples are collected for the infection analysis. Pups whose mothers received the synbiotic have lower RV infection severity. The levels of immunoglobulins (Ig) IgG2c and IgA are raised in pups’ plasma and digested milk, respectively. Synbiotic supplementation improves intestinal maturation and increases gene expression of immune-related genes. In conclusion, the administration of this synbiotic to gestating and lactating mothers ameliorates the incidence and severity of the pup’s diarrhea caused by the RV infection by improving their immunity.
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    Nanomotor-Assisted Intravesical Chemotherapy for Bladder Tumor Reduction and Suppression of Early Tumor Regrowth
    (American Chemical Society, 2026-05-06) Vilaseca, Antoni; Llop Talaverón, Josep Manuel; Sánchez-López, Sònia; Fichna, Kristin; Crespo Cuadrado, Maria; Konuparamban, Acsah; Di Carlo, Valerio; Esporrín Ubieto, David; Macías Tarrío, Irene; Jutglar Soler, Oriol; Chen, Shuqin; Gómez Martínez, María; Bakenecker, Anna C.
    Nanoparticles are widely used in nanomedicine for controlled drug delivery and improved bioavailability. However, their effectiveness is often limited by passive diffusion, especially in confined, fluid-filled environments like the bladder, where rapid drug clearance and uneven distribution reduce therapeutic impact. These challenges contribute to high recurrence in bladder cancer despite intravesical chemotherapy. To address this limitation, we present urease-powered nanomotors (NM) based on mesoporous silica nanoparticles loaded with Mitomycin C (MMC), the standard chemotherapeutic for nonmuscleinvasive bladder cancer. These NM useurea present in urine to induce motion and drug dispersion. In vitro, NM showed 2.3-fold higher uptake in mouse bladder cancer cells than passive nanoparticles and achieved the efficacy of free MMC (577.5 μg/mL) at a 20-fold lower dose (30 μg/mL). In vivo, a single intravesical dose reduced tumor volumes by 83% and prevented early tumor regrowth, demonstrating the potential of NM-based delivery for bladder cancer therapy.
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    Allosterism in the adenosine A2A and cannabinoid CB2 heteromer
    (Blackwell, 2024-07-23) Llinàs del Torrent, Clàudia; Raïch, Iu; González, Andrea; Lillo, Jaume; Casajuana-Martin, Nil; Franco Fernández, Rafael; Pardo, Leonardo; Navarro Brugal, Gemma
    Background and Purpose Allosterism is a regulatory mechanism for GPCRs that can be attained by ligand-binding or protein–protein interactions with another GPCR. We have studied the influence of the dimer interface on the allosteric properties of the A2A receptor and CB2 receptor heteromer. Experimental Approach We have evaluated cAMP production, phosphorylation of signal-regulated kinases (pERK1/2), label-free dynamic mass redistribution, β-arrestin 2 recruitment and bimolecular fluorescence complementation assays in the absence and presence of synthetic peptides that disrupt the formation of the heteromer. Molecular dynamic simulations provided converging evidence that the heteromeric interface influences the allosteric properties of the A2AR–CB2R heteromer. Key Results Apo A2AR blocks agonist-induced signalling of CB2R. The disruptive peptides, with the amino acid sequence of transmembrane (TM) 6 of A2AR or CB2R, facilitate CB2R activation, suggesting that A2AR allosterically prevents the outward movement of TM 6 of CB2R for G protein binding. Significantly, binding of the selective antagonist SCH 58261 to A2AR also facilitated agonist-induced activation of CB2R.
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    Unravelling the effect of parity on immunoglobulins, cytokines and adipokines in human transitional milk and their association with infant infections during the first 6 months of life
    (BioMed Central, 2025-10-06) Rio Aige, Karla; Martínez Costa, Cecilia; Castell, Margarida; Rodríguez Lagunas, María José; Collado, Maria Carmen; Pérez-Cano, Francisco J.
    Human milk dynamically adapts its composition of immunoglobulins (Igs), cytokines, and other proteins as lactation progresses, influencing the infant’s immune development and protection. Understanding how maternal factors, such as parity, influence the composition of human milk can provide strategies aimed at enhancing infant immune protection and reducing early-life infections. This study aims to investigate whether the immune composition of human milk differs based on parity, and if so, how these changes are related to infections in early life. Methods The study included 75 healthy mother-infant pairs from the MAMI cohort (Clinical Trial Registry NCT03552939), with milk samples collected from the same mothers at days 7 and 15 postpartum, during transitional lactation stage. Igs, cytokines, and adipokines were quantified using multiplex immunoassays and ELISA. A comparison was conducted between primiparous and multiparous mothers regarding both the overall and individual composition of immune components in human milk at each time point, as well as their evolution throughout the transitional phase. Results Infants from multiparous mothers recorded higher infection rates in early life than those of primiparous mothers. Some human milk immune components also differed by parity, with multiparous mothers exhibiting higher levels of IgA, total IgG, IgG1, IgG2, IgG3, IgE, and IL-23 at the beginning of the transitional phase (day 7), as well as higher IL-18 and IL-21 levels toward its end (day 15), compared to primiparous mothers. Additionally, the evolutionary pattern in levels of Igs, cytokines, and adipokines throughout the transitional milk stage also differed. Moreover, in multiparous mothers, higher levels of IgG, particularly IgG1 and IgG2 (day 7), as well as IL-18 and IL-22 (day 15), were associated with reduced infant infections, highlighting their potential protective role. Conclusions Parity is a maternal factor that influences some immune components of human milk during the transitional stage and may be linked to the susceptibility of infants to infections during the first 6 months of life. Future studies aimed at analyzing the impact of the parity factor, among others, on the progression of immune components in human milk may contribute to a better understanding and improved strategies for newborn health.
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    Increase in wasteosomes (corpora amylacea) in frontotemporal lobar degeneration with specific detection of tau, TDP‑43 and FUS pathology
    (BioMed Central, 2024-06-15) Sánchez del Valle Díaz, Raquel; Pelegrí, Carme; Molina Porcel, Laura; Vilaplana i Hortensi, Jordi; Alsina Planelles, Raquel; Riba Baqués, Marta; Pérez Millan, Agnès; Borrego Écija, Sergi; Aldecoa, Iban; Romera, Clara; Balasa, Mircea; Antonell Boixader, Anna, 1978-; Lladó Plarrumaní, Albert; Compta Y; Valle Domínguez, Jesús del
    Wasteosomes (or corpora amylacea) are polyglucosan bodies that appear in the human brain with aging and in someneurodegenerative diseases, and have been suggested to have a potential role in a nervous system cleaningmechanism. Despite previous studies in several neurodegenerative disorders, their status in frontotemporal lobardegeneration (FTLD) remains unexplored. Our study aims to characterize wasteosomes in the three primary FTLDproteinopathies, assessing frequency, distribution, protein detection, and association with aging or disease duration.Wasteosome scores were obtained in various brain regions from 124 post‑mortem diagnosed sporadic FTLD patients,including 75 participants with tau (FTLD‑tau), 42 with TAR DNA‑binding protein 43 (FTLD‑TDP), and 7 with Fusedin Sarcoma (FTLD‑FUS) proteinopathies, along with 29 control subjects. The wasteosome amount in each brainregion for the different FLTD patients was assessed with a permutation test with age at death and sex as covariables,and multiple regressions explored associations with age at death and disease duration. Double immunofluorescencestudies examined altered proteins linked to FTLD in wasteosomes. FTLD patients showed a higher accumulationof wasteosomes than control subjects, especially those with FTLD‑FUS. Unlike FTLD‑TDP and control subjects, wasteo‑some accumulation did not increase with age in FTLD‑tau and FTLD‑FUS. Cases with shorter disease duration in FTLD‑tau and FTLD‑FUS seemed to exhibit higher wasteosome quantities, whereas FTLD‑TDP appeared to show an increasewith disease progression. Immunofluorescence studies revealed the presence of tau and phosphorylated‑TDP‑43in the periphery of isolated wasteosomes in some patients with FTLD‑tau and FTLD‑TDP, respectively. Central inclu‑sions of FUS were observed in a higher number of wasteosomes in FTLD‑FUS patients. These findings suggest a role of wasteosomes in FTLD, especially in the more aggressive forms of FLTD‑FUS. Detecting these proteins, particularlyFUS, in wasteosomes from cerebrospinal fluid could be a potential biomarker for FTLD.
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    TGF-β2, EGF and FGF21 influence the suckling rat intestinal maturation
    (Elsevier B.V., 2025-01-01) Grases Pintó, Blanca; Torres-Castro, Paulina; Abril Gil, Maria del Mar; Castell, Margarida; Rodríguez Lagunas, María José; Pérez-Cano, Francisco J.; Franch, Aina
    Some of the growth factors present in breast milk, such as transforming growth factor-β (TGF-β), epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), play important roles in the development of the intestinal tract. The aim of this study was to determine the effect of a supplementation with TGF-β2, EGF and FGF21 on suckling rats intestinal maturation. For this purpose, Wistar rats were supplemented daily with TGF-β2, EGF or FGF21 throughout the suckling period. We evaluated the functionality of the intestinal epithelial barrier through an in vivo dextran permeability assay, and by a histomorphometric and immunohistochemical study. In addition, the intestinal gene expression of tight junction-associated proteins, mucins, toll-like receptors, and maturation markers was analyzed. Moreover, the intraepithelial lymphocyte (IEL) phenotypical composition was established. During the suckling period, the supplementation with TGF-β2, EGF and FGF21 showed important signs of intestinal maturation. These results suggest that these molecules, present in breast milk, play a modulatory role in the maturation of the intestinal barrier function and the IEL composition during the suckling period. Keywords: Breast milk; Growth factors; Intestinal barrier function; Intestinal immunity; Intraepithelial lymphocytes; Neonatal rats.