Maria Dolores Mauricio

Introduction: Hypertension contributes to cardiovascular disease, with growing evidence of sex-specific differences in its underlying mechanisms. T-type voltage-gated calcium channels (VGCCs) have emerged as key regulators of vascular tone, particularly under conditions of nitric oxide (NO) deficiency. However, their role in mediating vascular dysfunction across sexes remains poorly understood. Methods: This study examined the role of T-type VGCCs and their modulation by NO in the renal artery of male and female spontaneously hypertensive rats (SHR). Vascular reactivity was assessed through phenylephrine-induced contractions in the presence or absence of nickel chloride (NiCl ₂ ), a T-type VGCC blocker, and L-NAME, an inhibitor of nitric oxide synthase (NOS). Gene expression of T-type VGCCs (Ca _V 3.1 and Ca _V 3.2) and eNOS was quantified by RT-PCR. Oxidative stress parameters in leukocytes were assessed by flow cytometry to explore the systemic redox. Results: Hypertension induced a rightward shift of the acetylcholine-mediated vasorelaxation curve. In male rats, hypertension did not significantly alter the phenylephrine concentration-response curve. A single data point showed a significant difference following incubation with L-NAME. The contribution of T-type VGCCs to vascular reactivity remained unchanged. Male SHRs displayed increased mRNA expression of Ca _V 3.1, Ca _V 3.2, and eNOS, yet showed no corresponding increase in T-type VGCC activity or NO availability. Conversely, in female SHR, phenylephrine concentration-response curve showed a leftward shift, reduced NO release, and increased participation of T-type VGCCs in response to phenylephrine. Furthermore, pharmacological inhibition of NO synthesis in female WKY rats, used to simulate hypertensive conditions, enhanced the involvement of T-type VGCCs in phenylephrine-induced vasoconstriction. mRNA expression of eNOS was not modified by hypertension in females. Despite the heightened T-type VGCCs activity, female SHRs had reduced mRNA expression of Ca _V 3.1 and Ca _V 3.2, suggesting a potential compensatory downregulation. Finally, leukocytes of male SHR exhibited significantly increased production of H ₂ O ₂ and ONOO ⁻ compared to the other studied groups, suggesting that hypertension contributes to a greater oxidative stress in male. Discussion: These findings reveal sex-specific differences in the role of T-type VGCCs during hypertension and underscore the therapeutic potential of targeting T-type VGCCs, particularly in females, as a sex-specific strategy for more effective and personalized hypertension management.

T‐type voltage‐gated calcium channels (VGCCs) are comparatively understudied in large conduit artery function relative to the well‐characterized L‐type channel subtype. This study investigates the vascular roles of T‐type VGCCs in the aorta and renal artery of healthy rabbits using functional reactivity assays and immunofluorescence and further elucidates the interaction between T‐type VGCC activity and the nitric oxide (NO) signalling pathway. T‐type VGCCs contributed to contractile responses induced by phenylephrine and angiotensin II in both arteries. Moreover, in the renal artery, the contribution of T‐type VGCCs in response to phenylephrine increased in the absence of NO and was associated with endothelium‐dependent vasodilation. Immunofluorescence analysis revealed co‐localization of Ca _V 3.1 with endothelial nitric oxide synthase in the renal artery, but not in the aorta, suggesting a vasodilatory role in renal circulation. These findings highlight vascular bed‐specific functions of T‐type VGCCs and their interaction with endothelial pathways in the renal artery.

Este trabajo presenta una experiencia docente interdisciplinar desarrollada conjuntamente por profesorado de Biología y Fisiología, en la que se propone al alumnado la creación de animaciones (GIFs u otros formatos) como herramienta para integrar contenidos relacionados con la unión ligando-receptor y sus consecuencias en un proceso fisiológico. La actividad se realizó con estudiantes de primer curso del grado en Ingeniería Biomédica (UPV), organizados en grupos, y evaluada mediante rúbrica. Los resultados muestran un alto grado de implicación y calidad en los entregables, especialmente en aquellos que contextualizaron el proceso biológico. La experiencia fomenta el aprendizaje significativo, el trabajo en equipo además de la coordinación docente entre asignaturas. Se identificaron retos como la comunicación de problemas de participación, o problemas conceptuales que plantean la introducción de mejoras para futuras ediciones.

Aging is associated with increased oxidative stress, which contributes to cellular dysfunction and age-related diseases. Pomegranate extract (PE), rich in antioxidant polyphenols, may help mitigate oxidative damage. This study evaluated whether PE supplementation modulates oxidative stress by reducing reactive oxygen species (ROS) levels in white blood cells of aging mice. Aged mice (18 months) were supplemented with PE for four months, and cytoplasmic and mitochondrial ROS levels were assessed in leukocytes under basal conditions and oxidative stress conditions induced by tert-butyl hydroperoxide (t-BHP) using flow cytometry. Our results indicate that aged mice exhibit increased basal ROS levels in both the mitochondrial and cytoplasmic compartments, which were mitigated by PE supplementation. Furthermore, PE reversed the increase in hydrogen peroxide levels induced by τ-BHP and protected neutrophils by reducing mitochondrial ROS levels. These findings suggest that PE supplementation modulates the oxidative stress response, potentially improving immune function in aging. Given the central role of oxidative stress in age-related decline, PE may represent a valuable nutritional strategy to promote healthy aging.

Background/Objectives: Acute myocardial infarction (AMI) is a critical medical condition that requires immediate attention to minimise heart damage and improve survival rates. Early identification and prompt treatment are essential to save the patient’s life. Currently, the treatment strategy focuses on restoring blood flow to the myocardium as quickly as possible. However, reperfusion activates several cellular cascades that contribute to organ dysfunction, resulting in the ischaemia/reperfusion (I/R) injury. The search for treatments against AMI and I/R injury is urgent due to the shortage of effective treatments at present. In this regard, histone deacetylase (HDAC) inhibitors emerge as a promising treatment against myocardial infarction. The objective of this systematic review is to analyse the effects of HDAC inhibitors on ventricular function, cardiac remodelling and infarct size, among other parameters, focusing on the signalling pathways that may mediate these cardiovascular effects and protect against AMI. Methods: Original experimental studies examining the effects of HDAC inhibitors on AMI were included in the review using the PubMed and Scopus databases. Non-experimental papers were excluded. The SYRCLE RoB tool was used to assess risk of bias and the results were summarised in a table and presented in sections according to the type of HDAC inhibitor used. Results: A total of 18 studies were included, 10 of them using trichostatin A (TSA) as an HDAC inhibitor and concluding that the treatment improved ventricular function, reduced infarct size, and inhibited myocardial hypertrophy and remodelling after AMI. Other HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA), valproic acid (VPA), mocetinostat, givinostat, entinostat, apicidin, and RGFP966, were also analysed, showing antioxidant and anti-inflammatory effects, an improvement in cardiac function and remodelling, and a decrease in apoptosis, among other effects. Conclusions: HDAC inhibitors constitute a significant promise for the treatment of AMI due to their diverse cardioprotective effects. However, high risk of selection, performance, and detection bias in the in vivo studies means that their application in the clinical setting is still a long way off and more research is needed to better understand their benefits and possible side effects.

Probiotics are living microorganisms recognized for conferring health benefits on the host by modulating the gut microbiota. They interact with various signaling pathways, including the aryl hydrocarbon receptor (AhR), which plays a crucial role in maintaining intestinal homeostasis and immune function. The activation of AhR by probiotics has been associated with benefits such as improved intestinal barrier function, reduced inflammation, and modulation of immune responses. This systematic review aims to summarize current knowledge on the signaling of AhR, mediated by probiotics in physiological conditions and gastrointestinal pathologies. We conducted a comprehensive search across databases, including PubMed and Embase, up until July 2024. Out of 163 studies screened, 18 met the inclusion criteria. Our findings revealed in healthy populations that probiotic consumption increases the production of AhR ligands promoting intestinal immune tolerance. Furthermore, in populations with gastrointestinal pathologies, probiotics ameliorated symptoms through AhR activation by Trp metabolites, leading to the upregulation of the anti-inflammatory response.

El estudiantado del grado en Medicina tiene unos niveles de autoexigencia muy elevados. Sin embargo, su autonomía y autorregulación no están muy alineadas cuando acceden al grado, como se deduce de diferentes estudios sobre su estado de ánimo y sus tasas de ansiedad. Diseñar experiencias que permitan mejorar sus aprendizajes basadas en datos objetivos que alienten su trabajo es esencial. Presentamos unos materiales de integración de contenidos teórico-prácticos y de autoevaluación, que se ofrecen para el acceso libre por parte del alumnado. En esta experiencia, evaluamos la interacción que hacen con los materiales proporcionados y su repercusión sobre la calificación obtenida en diferentes facetas de la asignatura de Biología de 1er curso. De esta manera extraemos información sobre su motivación espontánea ante los recursos de aprendizaje, y por otro, confirmamos que el diseño ha sido adecuado para mejorar el desarrollo de competencias

Ante el alarmante aumento de la incidencia de enfermedades mentales en la población general, especialmente entre los jóvenes, la propuesta "FarmaSalud Mental" busca sensibilizar a los estudiantes del Grado de Farmacia sobre la importancia de la salud mental y empoderarlos como protagonistas activos en la búsqueda de soluciones. Este proyecto se desarrolla en los seminarios de la asignatura de Fisiopatología, en tercer curso, y se concibe como un espacio de acción inmediata y colaborativa. Los participantes abordan los desafíos de la salud mental desde diversas perspectivas, presentando propuestas que contribuyan al abordaje del tema y analizando su estado emocional antes y después del ejercicio. Este proyecto se realizó durante los cursos 22-23 y 23-24, y en sus resultados se destaca el impacto positivo de esta intervención en el aprendizaje y la gestión de los problemas emocionales del alumnado, así como en la integración de los ODS. Las propuestas presentadas refuerzan la percepción del papel activo y relevante de los futuros farmacéuticos en la promoción de la salud mental, subrayando la importancia de adoptar enfoques interdisciplinares y colaborativos para mejorar el bienestar general de la sociedad.

Levamisole is an anthelmintic drug restricted to veterinary use but is currently detected as the most widely used cocaine cutting agent in European countries. Levamisole-adulterated cocaine has been linked to acute kidney injury, marked by a decrease in glomerular filtration rate, which involves reduced renal blood flow, but data on the alteration of renovascular response produced by levamisole are scarce. Renal arteries were isolated from healthy rabbits and used for isometric tension recording in organ baths and protein analysis. We provide evidence that depending on its concentration, levamisole modulates renovascular tone by acting as a non-selective α-adrenergic receptor blocker and down-regulates α₁-adrenoceptor expression. Furthermore, levamisole impairs the endothelium-dependent relaxation induced by acetylcholine without modifying endothelial nitric oxide synthase (eNOS) expression. However, exposure to superoxide dismutase (SOD) partially prevents the impairment of ACh-induced relaxation by levamisole. This response is consistent with a down-regulation of SOD1 and an up-regulation of NADPH oxidase 4 (Nox4), suggesting that endothelial NO loss is due to increased local oxidative stress. Our findings demonstrate that levamisole can interfere with renal blood flow and the coordinated response to a vasodilator stimulus, which could worsen the deleterious consequences of cocaine use. Graphical Abstract EFS electric field stimulation, NA noradrenaline, AR adrenergic receptor, IP₃ inositol 1, 4, 5-trisphosphate, cAMP cyclic adenosine monophosphate, mAChR muscarinic acetylcholine receptor, eNOS endothelial nitric oxide synthase, sGC soluble guanylyl cyclase, SOD superoxide dismutase, NOX4 NAPH oxidase 4