Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

URI permanent per a aquesta col·leccióhttps://hdl.handle.net/2445/20403

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Extracellular vesicles participate in proteostasis and heat shock adaptation in Plasmodium falciparum
(Taylor & Francis, 2026-06-26) Avalos Padilla, Yunuen; Román Álamo, Lucía; Bouzón Arnáiz, Inés; Martínez Arce, Elsa; Muñoz-Torrero López-Ibarra, Diego; Fernàndez Busquets, Xavier
Heat shock is a hallmark of clinical malaria, where Plasmodium falciparum parasites are exposed to recurrent febrile episodes exceeding 40 °C, which lead to acute proteotoxic stress. Parasite survival under these conditions relies on efficient proteostasis mechanisms and molecular chaperones, yet how stress resilience is coordinated beyond chaperone responses remains poorly understood. Here, we identify a stress-associated role for extracellular vesicles (EVs) in parasite heat shock adaptation linked to vesicular trafficking mediated by PfVps60, an Endosomal Sorting Complex Required for Transport (ESCRT) protein. Using a PfVps60 knockout (PfVps60KO) line, we show that disruption of ESCRT-dependent vesicular trafficking affects EV cargo composition during thermal stress. Proteomic profiling revealed that 44.8% of EV-associated proteins from P. falciparum 3D7 overlapped with a previously defined set of aggregation-prone proteins. Loss of PfVps60 impaired EV-mediated export of the chaperones PfHsp70-x and PfHsp110, altered aggregation dynamics and induced the redistribution of protein aggregates near the parasitophorous vacuole, reduced induction of the cytosolic chaperone PfHsp70-1, and resulted in early loss of parasite viability following heat shock. Supplementation of PfVps60KO parasites with EVs derived from heat-stressed 3D7 parasites partially rescued heat shock tolerance in a dosedependent manner. EVs released shortly after thermal stress were enriched in aggregation-prone proteins and associated with neighbouring uninfected erythrocytes, suggesting EV-mediated intercellular communication during febrile episodes. Together, these findings support a role for EV-associated cargo as a previously unexplored component of P. falciparum proteostasis during heat shock adaptation, identifying stress-induced EVs as a potential parasite vulnerability for malaria intervention.
Cocrystals of β-Sitosterol with Propionic Acid ImprovePostprandial Lipid Response and Long-Term Adaptation toObesogenic Diets in Hamsters, Surpassing the Effects ofCommercial β-Sitosterol
(MDPI, 2026-07-02) Palou, Mariona; Reynés, Barbara; Prohens López, Rafael; Barrera, Fernando; Palou, Andreu; Serra, François; Palou-March, Andreu
This study investigated the short- and long-term metabolic effects of two β-sitosterol with propionic acid cocrystals (CCA and CCB) compared with commercial β-sitosterol in male hamsters.
AAV-mediated FGF21 gene therapy promotes health span extension by whole-body tissue-specific adaptations
(Cell Press, 2026-08) Marcó, Sara; Molas Laplana, Maria; Ribera Sánchez, Albert; Elias, Ivet; Rodó Tomás, Jordi; Ferré Masferrer, Tura; Bosch i Tubert, Fàtima; Jiménez Perales, Verónica; Sacristán, Víctor; Garcia, Miquel; Jambrina, Claudia; Casana, Estefania; Muñoz, Sergio; Vilà Prats, Laia; Grass, Ignasi; Jaén, Maria Luisa; Roca, Carles; León, Xavier
The decline of organ function during aging limits health span. Despite the potential of lifestyle interventions to improve health, sustained maintenance of health span is challenging, and no gerotherapeutic drugs have been approved. Here, we demonstrated that aged and geriatric male and female mice treated with muscle-directed adeno-associated viral (AAV) vector-mediated fibroblast growth factor 21 (FGF21) gene therapy extended health span and lifespan with sustained organ benefits. This treatment normalized body weight and adiposity, improved insulin sensitivity and glucose homeostasis, preserved hepatic detoxification capacity, counteracted age-related kidney disease, promoted cardiac health and muscular function, and enhanced cognition. Transcriptomic and histopathological analyses indicated improved whole- body energy homeostasis and cellular fitness, which were mediated by tissue-specific adaptations, including enhanced mitochondrial function, restored proteostasis, and reversion of inflammation, fibrosis, and amyloidosis. AAV-FGF21 treatment also activated AMPK signaling. These results highlight FGF21 gene therapy as a potential strategy to promote health span and delay age-related deterioration.
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.
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.
Prescription Trends and Clinical Decision‐Making in Neuropathic Pain Pharmacological Treatment: Results From a Cross‐Sectional Survey by the Spanish Pain Society
(John Wiley & Sons, 2026-03-01) Á. Huerta, Miguel; Mayo‐moldes, Mónica; M. Garcia, Miguel; García‐parra, Beliu; Matute, Mercè; López‐tofiño, Yolanda; Paniagua, Nancy; Hernández‐secorún, Mar; Soler, Dolors; Salmerón, Marcos; Taylor, Julian; Verdú, Enrique; A. Valencia, José; Pico, Silvia; Díaz‐alejo, Clara; Katsuki, Masahito; Serrano‐afonso, Ancor; Ruiz‐cantero, M. Carmen
Background: Neuropathic pain (NP) is a complex chronic condition with limited therapeutic effectiveness. Despite multiple drug classes and international guidelines, real-world adherence remains inconsistent, and data on prescribing practices among pain specialists is scarce. Methods: We conducted a nationwide cross-sectional survey among members of the Spanish Pain Society in May 2025. A structured 62-item questionnaire assessed prescribing habits, decision-making criteria, guideline adherence, dosage patterns, and the recognition and management of tolerance. Sociodemographic and professional data were also collected. Results: A total of 220 pain specialists (52% female) completed the survey; 28% had over 20 years of clinical experience. Satisfaction with current pharmacological options was modest, with 52% reporting dissatisfaction or indifference. Prescribing was mainly guided by clinical experience (43%) and guideline recommendations (36%). Gabapentin (45%) and pregabalin (40%) were the most frequent first-line choices, followed by tricyclic antidepressants (amitriptyline; 9%), duloxetine (5%) and venlafaxine (1%). Tramadol dominated second-line use (65%), followed by capsaicin (22%) or lidocaine (5%) patches. Half of the participants reported tolerance, typically after 3-12 months, managed mainly by dose escalation or switching drug classes. Dosage practices for gabapentinoids and antidepressants showed marked heterogeneity, with frequent deviations from recommended titration protocols. Conclusions: NP management in Spain shows variability and partial alignment with international guidelines. Gabapentinoids, tricyclic antidepressants and duloxetine remain preferred treatments, but reliance on personal experience and awareness of tolerance hinder evidence-based practice. Quantifying Spanish pain specialists' views on tolerance supports calls for national consensus, better dosing education and further research to harmonise care and improve outcomes. Significance: This nationwide survey provides the first systematic assessment of neuropathic pain management in Spain, revealing marked variability, only partial adherence to international guidelines, and persistent reliance on clinical experience over evidence. It confirms gabapentinoids, tricyclic antidepressants and duloxetine as preferred treatments, identifies continued tramadol use despite conflicting recommendations, and quantifies for the first time clinicians' perception and management of tolerance. These findings fill a major evidence gap and directly inform future national consensus, educational initiatives and clinical practice improvement.
Supercooled liquid state facilitates recrystallization-mediated gelation of amorphous cinnarizine
(Wiley, 2026-08-01) Li, Yi; Teng, Manlin; Han, Sining; Si, Huijie; Prohens López, Rafael; Fu, Qiang; Li, Mingzhong
Amorphization is an effective strategy for enhancing the solubility of poorly water-soluble drugs. However, its benefits can be compromised by gelation-a counterintuitive phenomenon that leads to decreased dissolution behavior compared to the crystalline counterpart. In this study, we found that amorphous cinnarizine (CIN) exhibits a pronounced gelation tendency at higher pH, temperature, and ionic strength. We propose that the gelation process is initiated by CIN’s transition into a supercooled liquid state above its glass transition temperature (Tg). This state is characterized by high viscosity but sufficient molecular mobility, which collectively facilitates rapid recrystallization and subsequent gel network formation. This study elucidates the underlying mechanism and offers a perspective for preventing gelation in low-Tg amorphous drugs.
Structure-based virtual screening, in vitro and in silico analysis identified novel potent m6A demethylase FTO inhibitors as promising neurotherapeutic agents
(Elsevier Masson SAS, 2026-04-09) Brea, José; Val, Cristina; Pallàs i Llibería, Mercè, 1964-; Muñoz-Torrero López-Ibarra, Diego; Griñán Ferré, Christian; Irisarri, Alba; Bellver Sanchis, Aina; Choudhary, Bhanwar Singh; Mallo Abreu, Ana; Labrador, Luis; Casadesús, Gemma; Pérez, Belén; Jana, Abhisek; Banerjee, Deb Ranjan; Iriepa, Isabel; Loza, María Isabel
Dysregulation of the m6A RNA demethylase FTO has been implicated in neurodegeneration, but brain-penetrant, selective inhibitors remain scarce. Here, we used structure-based virtual screening of a CNS-oriented library to identify novel FTO inhibitors and characterized their permeability, selectivity, and pharmacological profiles. Among them, compound VI showed low-micromolar inhibition of human FTO, selectivity over ALKBH5, high PAMPA-BBB permeability, and oral exposure with measurable plasma levels, moderate brain penetration, and CSF detectability. Molecular dynamics simulations confirmed stable binding of VI within the FTO catalytic pocket, consistent with its enzymatic potency and selectivity. In differentiated SH-SY5Y cells, VI protected against Aβ1-42-induced toxicity while increasing global m6A levels and dampening pro-inflammatory gene expression. In SAMP8 mice, chronic oral treatment with VI (3 mg/kg) ameliorated anxiety-like behavior and rescued hippocampal-dependent spatial and recognition memory, concomitant with increased brain m6A and normalization of synaptic and neuroinflammatory markers. Overall, our findings identify compound VI as a selective, brain-penetrant FTO inhibitor with favorable pharmacokinetics and disease-modifying efficacy in a sporadic Alzheimer's disease model, supporting its further development as a neurotherapeutic candidate.
Polymorphism in the 1/1 Pterostilbene/Picolinic Acid Cocrystal
(American Chemical Society, 2022-01-22) Barbas Cañero, Rafael; Font Bardia, Ma. Mercedes; Frontera, Antonio; Prohens López, Rafael
The crystal structures of two new polymorphs of the 1/1 pterostilbene/picolinic acid cocrystal have been analyzed by single-crystal X-ray diffraction and studied by means of DFT calculations and a set of computational tools (QTAIM, NCIplot, MEP). The observation of a new R22(10) synthon in each of the two polymorphs has been analyzed energetically, characterized using the topology of the electron density, and rationalized using the MEP surfaces. The exceptional bioavailability of the cocrystal is explained on the basis of BFDH morphology calculations, and the study is complemented by a deep analysis of the supramolecular synthons formed by both neutral and zwitterionic forms of picolinic acid, a versatile coformer for crystal engineering.
From the Design to the In Vivo Evaluation of Benzohomoadamantane-Derived Soluble Epoxide Hydrolase Inhibitors for the Treatment of Acute Pancreatitis.
(American Chemical Society, 2021-05-13) Griñán Ferré, Christian; Pallàs i Llibería, Mercè, 1964-; Sanfeliu, Coral; Vázquez Carrera, Manuel; Hammock, Bruce D.; Feixas, Ferran; Vázquez Cruz, Santiago; Codony Gisbert, Sandra; Calvó-Tusell, Carla; Valverde Murillo, Elena; Osuna, Sílvia; Morisseau, Christophe; Loza, María Isabel; Brea, José; Pérez, Concepción; Rodríguez-Franco, María Isabel; Pizarro Delgado, Javier; Corpas, Rubén
The pharmacological inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Numerous potent sEH inhibitors (sEHIs) present adamantyl or phenyl moieties, such as the clinical candidates AR9281 or EC5026. Herein, in a new series of sEHIs, these hydrophobic moieties have been merged in a benzohomoadamantane scaffold. Most of the new sEHIs have excellent inhibitory activities against sEH. Molecular dynamics simulations suggested that the addition of an aromatic ring into the adamantane scaffold produced conformational rearrangements in the enzyme to stabilize the aromatic ring of the benzohomoadamantane core. A screening cascade permitted us to select a candidate for an in vivo efficacy study in a murine model of cerulein-induced acute pancreatitis. The administration of 22 improved the health status of the animals and reduced pancreatic damage, demonstrating that the benzohomoadamantane unit is a promising scaffold for the design of novel sEHIs.
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.
GADD45A: With or without you
(Wiley, 2024-07-01) Palomer Tarridas, Francesc Xavier; Salvador, Jesús M.; Griñán Ferré, Christian; Barroso Fernández, Emma; Pallàs i Llibería, Mercè, 1964-; Vázquez Carrera, Manuel
The growth arrest and DNA damage inducible (GADD)45 family includes three small and ubiquitously distributed proteins (GADD45A, GADD45B, and GADD45G) that regulate numerous cellular processes associated with stress signaling and injury response. Here, we provide a comprehensive review of the current literature investigating GADD45A, the first discovered member of the family. We first depict how its levels are regulated by a myriad of genotoxic and non-genotoxic stressors, and through the combined action of intricate transcriptional, posttranscriptional, and even, posttranslational mechanisms. GADD45A is a recognized tumor suppressor and, for this reason, we next summarize its role in cancer, as well as the different mechanisms by which it regulates cell cycle, DNA repair, and apoptosis. Beyond these most well-known actions, GADD45A may also influence catabolic and anabolic pathways in the liver, adipose tissue and skeletal muscle, among others. Not surprisingly, GADD45A may trigger AMP-activated protein kinase activity, a master regulator of metabolism, and is known to act as a transcriptional coregulator of numerous nuclear receptors. GADD45A has also been reported to display a cytoprotective role by regulating inflammation, fibrosis and oxidative stress in several organs and tissues, and is regarded an important contributor for the development of heart failure. Overall data point to that GADD45A may play an important role in metabolic, neurodegenerative and cardiovascular diseases, and also autoimmune-related disorders. Thus, the potential mechanisms by which dysregulation of GADD45A activity may contribute to the progression of these diseases are also reviewed below.
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.
Structure-Activity Relationship of Synthetic Cathinones: An Updated Review
(American Chemical Society, 2024-09-13) Nadal-Gratacós, Núria; Pazos, Martalu D.; Pubill Sánchez, David; Camarasa García, Jordi; Escubedo Rafa, Elena; Berzosa, Xavier; López Arnau, Raúl
The escalating prevalence of new psychoactive substances (NPSs) poses a significant public health challenge, evidenced by the vast chemical diversity, with over 500 substances reported annually to the United Nations Office on Drugs and Crime-Early Warning Advisory (UNODC-EWA) in the past five years. Among NPSs, synthetic cathinones are gaining a lot of popularity among users. Notably, synthetic cathinones accounted for approximately 50% of the total quantity of NPSs reported as seized by EU Member States in 2021. Preliminary data from UNODC indicates that a total of 209 synthetic cathinones have been reported to date. As their popularity grows, studying the structure–activity relationship (SAR) of synthetic cathinones is essential. SAR studies elucidate how structural features impact biological effects, aiding in toxicity prediction, regulatory compliance, and forensic identification. Additionally, SAR studies play a pivotal role in guiding drug policies, aiding authorities in categorizing and regulating newly emerging synthetic cathinones, mitigate public health risks and offer valuable insights into potential therapeutic applications. Thus, our Review consolidates recent findings on the effects of different substitutions in the chemical scaffold of synthetic cathinones on their mechanism of action as well as pharmacological and toxicological effects of synthetic cathinones, thus enhancing understanding of the SAR of synthetic cathinones’ pharmacology and potential implications.
Effective oral countermeasures against ionizing radiation-induced damagewithout hindering cancer radiotherapy
(Elsevier Masson SAS, 2026-04-06) López-Blanch, Rafael; Oriol-Caballo, María; Salvador-Palmer, Rosario; Moreno-Murciano, Paz; Benlloch, María; Villaescusa, Juan I.; Montoro, Alegría; Prohens López, Rafael; Albertí, Joan; Estrela, José M.; Obrador, Elena
High-dose ionizing radiation induces severe multi-organ injury, yet no broadly effective, orally available countermeasure has been validated. Here we describe a fully oral, multi-component formulation comprising bioavailable polyphenol derivatives (pterostilbene cocrystals and silybin-phosphatidylcholine), the NAD⁺ precursor nicotinamide riboside, and captopril, an angiotensin-converting enzyme inhibitor with established radiomitigative activity that synergizes with the polyphenols. This combination provides robust systemic radioprotection, enabling long-term survival in 90% of mice exposed to a lethal (LD50/30) dose of X-rays. Mechanistically, the formulation mitigates hematopoietic, intestinal, and neuromotor injury while enhancing DNA repair, suppressing oxidative stress, preserving NAD⁺ homeostasis, and activating autophagy. In intestinal epithelial cells, it markedly reduces radiation-induced apoptosis, inflammatory signaling, and mitochondrial dysfunction through coordinated modulation of Nrf2, NF-κB, and sirtuin-regulated stress responses. Critically, normal tissue protection does not compromise tumor control. In triple-negative breast cancer models, irradiation-induced tumor regression is preserved, whereas in glioblastoma (a typically radioresistant malignancy) tumor radiosensitivity is significantly enhanced via sustained oxidative stress, reduced PARP1 expression, and inhibition of HIF-1α and VEGF signaling. Collectively, these findings define an orally deployable, mechanistically integrated strategy that protects normal tissues while preserving or augmenting tumor radiosensitivity, supporting its translational potential as a practical and effective countermeasure against ionizing radiation exposure.
Is Helicobacter pylori a new kid on the block?
(Elsevier España, 2024-02-23) Vázquez Carrera, Manuel
It is well known that traditional risk factors for atherosclerosis, such as age, smoking, diabetes mellitus, dyslipidemia, hypertension, and chronic inflammation, only account for approximately 50% of the incidence of atherosclerosis.1 Therefore, identifying new risks factors that contribute to atherosclerosis development may help to better recognize people with a high cardiovascular risk in the early stages of the disease.
Advancing personalized medicine in neurodegenerative diseases: The role of epigenetics and pharmacoepigenomics in pharmacotherapy
(Elsevier B.V., 2024-06-02) Griñán Ferré, Christian; Bellver Sanchis, Aina; Guerrero López, Ana; Pallàs i Llibería, Mercè, 1964-
About 80 % of brain disorders have a genetic basis. The pathogenesis of most neurodegenerative diseases is associated with a myriad of genetic defects, epigenetic alterations (DNA methylation, histone/chromatin remodeling, miRNA dysregulation), and environmental factors. The emergence of new sequencing technologies and tools to study the epigenome has led to identifying predictive biomarkers for earlier diagnosis, opening up the possibility of prophylactical interventions. As a result, advances in pharmacogenetics and pharmacoepigenomics now allow for personalized treatments based on the profile of each patient and the specific genetic and epigenetic mechanisms involved. This Review highlights the complexity of neurodegenerative diseases and the variability in patient responses to pharmacotherapy, emphasizing the influence of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of drugs used to treat those conditions. We specifically discuss the potential modulatory effect of several genetic polymorphisms associated with an increased risk of developing different neurodegenerative diseases. We explore genetic and genomic technologies and the potential of analyzing individual-specific drug metabolism to predict and influence drug response and associated clinical outcomes. We also provide insights into the mechanism of action of the drugs under investigation and their potential impact on disease-modifying pathways. Finally, the Review underscores the great potential of this field to enhance the effectiveness and safety of drug treatments through personalized medicine.
Ring-closing metathesis studies in the context of the formal synthesis of themarine macrolide (–)-callyspongiolide
(Michigan Publishing, 2025-09-11) Urbina, Andrea; Calbó Zabala, Arnau; Llor Brunés, Núria; Bosch Mestres, Jordi; Amat Tusón, Mercedes
Attempts to synthesize the natural product macrolide polyketide (–)-callyspongiolide have drawn great interestbecause of its potent cytotoxic activity. Its total synthesis has proven to be difficult, however, due to itschallenging structure. The influence of the configuration of a homoallylic stereocenter on the closure of a 14-membered macrocyclic carbonate by ring-closing metathesis (RCM) from two epimeric dienes is described. Theresults offer some insights into the structural features which contribute to hampering the closure of themacrocyclic core of the macrolide polyketide. A formal synthesis of the marine macrolide (–)-callyspongiolide isalso reported using a RCM approach (C10-C11 bond formed) from analogous dienes bearing an α,β-unsaturatedester instead of a carbonate
Visualizing nanostructures in supramolecular hydrogels: a correlative study using confocal and cryogenic scanning electron microscopy
(Beilstein Institute, 2025-12-01) Smith, Shaun S.; Malagreca, Ferdinando; Hicks, Jacqueline M.; Mantovani, Giuseppe; Amabilino, David B.; Parmenter, Christopher; Pérez García, M. Lluïsa (Maria Lluïsa)
Solvated supramolecular hydrogels present unique challenges in nanoscale morphological characterization because of their fragilefibrous nature and low concentration of the solid component. In this study, imidazolium-based hydrogels containing either diketopyrrolopyrrole(DPP) or zinc(II) phthalocyanine (ZnPc) fluorophores were imaged using confocal laser scanning microscopy(CLSM) of fully solvated gels and cryogenic scanning electron microscopy (cryo-SEM) was used to observe the correspondingxerogels. The DPP@Gel systems exhibit strong fluorescence and are effectively imaged using CLSM, with fibre morphologies thatclosely correlate with those seen with cryo-SEM. In contrast, the analogous imidazolium gel system containing a sulfonated zincphthalocyanine (ZnPc@Gel) yields poor CLSM images because of the relatively weak emission and sample disruption duringcompression, whereas cryo-SEM enables clear visualization of the native fibrous network. These results demonstrate the complementarynature of CLSM and cryo-SEM and highlight the value of cryo-SEM as a very useful tool for imaging soft nanomaterialswith low fluorescence or limited optical contrast.
Liposomal formulations for waterproofing mucosal membranes
(Elsevier B.V., 2025-08-01) Coderch Negra, Ma. Luisa; Ricci, Lucia; Martí, Meritxell; Bagherpour, Saman; Pérez García, M. Lluïsa (Maria Lluïsa); Alonso, Cristina
Liposome formulations consisting of lipids contained in the stratum corneum have been recently demonstrated todecrease the permeability of mucosae. The permeability barrier of the mucosa is dependent on the presence ofspecific lipids. The main objective of this work is to reinforce the barrier effect of the oral mucosa with liposomalformulations to decrease permeation. Due to the high similarity in composition and structure between lanolinand human stratum corneum lipids, liposomes were formed with lipids contained in the stratum corneum withtwo kinds of ceramide or with lanolin. Transmembrane water loss of the two formulations was assessed,obtaining an important diminution for both liposomal formulations. Caffeine, lidocaine, ketoprofen and ivermectinand a virus model were tested on mucosa and on modified mucosa to evaluate the liposomal efficacy.A somewhat consistent permeation pattern was obtained for the different membranes: caffeine > lidocaine >ketoprofen > ivermectin. For all drugs and for the virus model, the most effective formulation was the liposomalformulation, consisting of lipids found in the horny layer of the skin. The effect of the lanolin on the transmembranewater loss is not reflected on the drug permeation. Therefore, it is demonstrated the main role ofceramides in the barrier function for drugs and a virus model. Strengthening the barrier function of the mucosapromotes the prevention or reduction of the permeation of different actives, which could be to extrapolate toharmful actives like viruses, pollutants, toxins, contaminants, etc.

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