Health Research Institute of the Balearic Islands

Oleocanthal (OC), an anti-inflammatory and antioxidant phenolic compound exclusively found in extra virgin olive oil (EVOO), has emerged as a potential anticancer agent through multiple mechanisms of action, yet its impact on key processes such as cellular metabolism remains insufficiently characterized. Here, we investigated the metabolic and mitochondrial responses to OC across different breast cancer molecular subtypes. Triple-negative (MDA-MB-231) and luminal (MCF7, T47D) breast cancer cell lines were treated with OC to evaluate cell viability, cell cycle progression, metabolic enzyme expression, mitochondrial respiration, and mitochondrial network organization. OC responsiveness differed, being highest in MDA-MB-231 and lowest in T47D cells. Lactate dehydrogenase levels decreased in all cell lines, while mitochondrial response varied. MDA-MB-231 mitochondrial function was fully impaired, while MCF7 cells showed increased respiratory activity, with marked mitochondrial fragmentation, and T47D cells largely preserved mitochondrial integrity and function. Notably, the magnitude of OC effects correlated with MET expression, an established target of OC and a prognostic factor associated with reduced relapse-free survival within the triple-negative subtype. Collectively, these findings identify OC as a modulator of cancer cell metabolism and mitochondrial dynamics, with particular relevance in MET-high triple-negative breast cancers.

Metabolomic studies in COPD reveal systemic metabolic perturbations, yet sex is often treated as a covariate rather than a biological driver. We aimed to identify plasma metabolites differentiating COPD from controls and to define sex-specific metabolic signatures in both groups. Methods: In this controlled observational study (BIOMEPOC cohort), untargeted plasma metabolomics was performed by LC-MS/MS. Differential abundance was tested across four contrasts (COPD vs. controls; men vs. women within controls; men vs. women within COPD; sex-by-disease interaction) with a false discovery rate (FDR) correction. Because smoking history differed between COPD and controls, a post hoc ever-smokers analysis was conducted. Results: COPD differed from controls in nine metabolites (all decreased): DL-stachydrine, 3-methyl-L-histidine, fructose, pipecolinic and nipecotic acids, 5-nitro-o-toluidine, conjugated linoleic acid, aminoadipate, and creatinine. This pattern is compatible with metabolic depletion, remodeling, and/or altered flux across multiple compartments rather than simple substrate deficiency, spanning muscle-related pools, amino acid handling, carbohydrate-associated metabolism, and exposome-linked inputs. In ever-smokers, results were directionally consistent, with five metabolites remaining nominally significant. Among controls, five metabolites were higher in men after FDR correction (PABA, cis-4-hydroxy-D-proline, N-acetylasparagine, deoxycarnitine, and creatinine), consistent with physiological sex dimorphism in energy pathways, connective-tissue remodeling, and diet/microbiome-related metabolism. Within COPD, six metabolites differed by sex after FDR correction, defining three axes: creatine energy buffering (men: higher GAA/creatinine, lower creatine), purine/urate handling (men: higher urate), and conjugated bile acids (men: higher GCDCA), implicating muscle bioenergetics, redox/inflammatory tone, and gut-liver crosstalk. Conclusions: Plasma metabolomics identifies a pattern compatible with systemic remodeling in COPD and sex-associated divergences in creatine, purine/urate, and bile-acid pathways, supporting a sex-influenced view of systemic COPD heterogeneity and highlighting targets for mechanistic validation.

During the past decade, our group has induced electroconvulsive seizures (ECS) in rodent models of early-life stress to prove clear differences in antidepressant-like efficacy mainly driven by sex and age, with females and adolescents showing diminished responses (as opposed to males and adult rodents). Moreover, we have proven a role for sex hormones in this response, since letrozole, an inhibitor of the biosynthesis of estrogens, improved the antidepressant-like efficacy of ECS in adolescent female rats. In this follow-up study, we utilized selective estrogen receptor modifiers (tamoxifen and clomiphene) to evaluate how they interact with the antidepressant-like response induced by ECS in male and female adolescent rats. Early-life stressed Sprague-Dawley rats through maternal separation were treated during adolescence with tamoxifen (1 mg/kg, 7 days) or clomiphene (10 mg/kg, 5 days) and/or with ECS (95 mA, 0.6 s, 100 Hz, 1 session/day, 5 days). Antidepressant-like responses were measured behaviorally under the stress of the forced-swim test, and through hippocampal markers (cell proliferation and neurogenic differentiation, and BDNF protein level). The main results proved that tamoxifen improved the expected antidepressant-like response of ECS in adolescent rats, as observed in the forced-swim test, while boosted hippocampal proliferation and neurogenic differentiation. Contrarily, clomiphene did not alter ECS' response at the behavioral level and even showed some negative signs on the neuroplasticity markers evaluated (decreased neurogenic differentiation and BDNF content). Therefore, when considering an estrogen receptor modifier to enhance the antidepressant-like potential of ECS in adolescence, tamoxifen emerges as a promising option due to its positive behavioral and neuroplastic effects.

Background Real-world evidence concerning the cardiovascular (CV) risk of umeclidinium (UMEC) monotherapy or UMEC/vilanterol (VI) is scarce. This real-world study investigated CV risk in new users of UMEC or UMEC/VI versus new users of tiotropium (TIO) in patients with chronic obstructive pulmonary disease (COPD). Methods This prospective, observational, multinational, cohort study enrolled patients ≥18 years with COPD who initiated UMEC, UMEC/VI or TIO between 2 February 2016 and 31 January 2023. Non-inferiority (95% confidence interval [CI] upper bound <2.0) of UMEC and UMEC/VI to TIO was compared for the time-to-first event (hazard ratio [HR] over 24 months) of a composite CV endpoint of myocardial infarction, stroke, heart failure or sudden cardiac death. Stabilised inverse probability of treatment weighting adjusted for differences in baseline covariate balance between groups. Incidence rates for the composite CV endpoint were calculated. Results In total, 6606 patients were enrolled; 6165 were included in the analysis. Both UMEC (n=1246) and UMEC/VI (n=2448) were non-inferior to TIO (n=2471) for the risk of the composite CV endpoint (adjusted HR [95% CI]: UMEC versus TIO: 1.254 [0.830–1.896]; UMEC/VI versus TIO: 1.352 [0.952–1.922]). Unadjusted composite CV incidence rates were low across cohorts (incidence rate [95% CI] per 100 person-years: UMEC: 1.157 [0.814–1.594]; UMEC/VI: 1.287 [1.034–1.584]; TIO: 0.924 [0.716–1.174]). Conclusions Both UMEC and UMEC/VI were non-inferior to TIO for composite CV risk, suggesting that physicians may consider escalating patients to dual bronchodilator therapy if COPD symptoms are not effectively managed with monotherapy.

Purpose: Mental fatigue resulting from prolonged cognitive activity leads to tiredness and decreased performance, particularly among university students. Active breaks (ABs) are short exercise sessions designed for use in the classroom, helping to alleviate stress and counteract the effects of prolonged sitting. This study aimed to evaluate the effectiveness of an AB programme on the psychological determinants of academic performance (motivation, attention, mood and mental fatigue) among university students. Method: A quasi-experimental design with pre- and post-repeated measurements was conducted with 96 undergraduate students (73.6% male, 26.4% female) in Mallorca, Spain. The intervention involved 3- to 5-minute ABs over 10 weeks, with two breaks per week. The order of conditions (AB/without AB) was counterbalanced. A visual analogue scale was used at the beginning, middle and end of the class to assess relevant psychological determinants. Results: All mid-class measurements were significantly better in the AB condition compared to the condition without ABs. The AB condition had higher mean scores than the non-AB condition for motivation (7.07 vs 5.91), attention (6.83 vs 5.90) and mood (7.19 vs 6.41). The AB condition also showed less mental fatigue (4.80 vs 5.38). Conclusion: ABs are efficacious in improving attention, motivation and mood while reducing mental fatigue among university students. These beneficial effects seem to be immediate but temporary, suggesting that ABs should be integrated into classroom routines on an ongoing basis in order to maintain their impact on psychological performance.