Dpto. Biología Celular, Genética, Histología y Farmacología

Decreased expression of insulin-degrading enzyme increases gluconeogenesis and glucose production in cultured hepatocytes administered with glucagon

2026-02-26T20:00:30Z

Insulin-degrading enzyme (IDE) is a protein with proteolytic and non-proteolytic functions that regulates glucose homeostasis. In the fasted state, glucagon regulates glycemia through induction of hepatic gluconeogenesis. The rate of hepatic gluconeogenesis is elevated in subjects with type 2 diabetes (T2D) compared with healthy subjects. Interestingly, subjects with T2D show decreased expression of hepatic IDE. However, the role of IDE on the regulation of hepatic gluconeogenesis is completely unknow. We hypothesize that IDE deficiency alters glucagon signaling and thereby gluconeogenesis. To test this hypothesis, we used mouse liver tissues and cultured hepatocytes with total or partial IDE deficiency. The glucagon signaling pathway, expression of gluconeogenic genes, glucose production, and transcriptomic analysis were performed in control and IDE-KO hepatocytes. Total or partial loss of IDE in liver tissues or cultured mouse hepatocytes resulted in lower levels of the glucagon receptor (GCGR) and the cAMP-response element binding protein (CREB). However, glucagon stimulation increased the phosphorylation of CREB, despite lower levels of cAMP in IDE-deficient mouse hepatocytes. The activation of CREB was associated with an upregulation of the gluconeogenic genes Pck1 and G6pc (~ 200% and ~ 70% respectively) and higher glucose production in IDE-deficient mouse hepatocytes. Finally, genetic depletion of IDE in HepG2 hepatocytes led to upregulation of genes involved in cellular functions related to membranes, organelles and signaling receptors. These findings may be of relevance to better understand the regulation of hepatic gluconeogenesis and the use of IDE as a potential therapeutic target for the treatment of T2D.

Potential Effect of Plasma Rich in Growth Factors-Endoret in Stromal Wound Healing in Additive Surgery

2026-03-16T12:22:17Z

Purpose: To compare the clinical and histological outcomes after intrastromal corneal ring segment (ICRS) implantation with and without plasma rich in growth factors (PRGF) in an experimental animal model. Materials and Methods: First, the toxicity of PRGF was tested in hen’s keratocyte cultures. Then, an animal model with 18 hens was randomly divided into 2 groups. In the first group, one ICRS was implanted in each eye (ICRS group). In the second group, the ICRS was firstly immersed 30 min in PRGF-Endoret solution, then implanted and, finally, PRGF-Endoret was inoculated into the channel (PRGF-ICRS group). Animals of each group were also separated into 3 groups regarding the time they were sacrificed, and corneal tissue was fixed for histological analysis at 2, 7 and 30 days. Cell death was detected by terminal uridine nick end labelling (TUNEL) assay. Proliferation was labelled by 5-bromo-2-deoxyuridine (BrdU) incorporation and myofibroblast differentiation by alpha-smooth muscle actin (αSMA) immunodetection. Clinical examination, analyzing epithelial wound closure, deposits and stromal haze, was carried out at the different study times. Results: No toxic effect was observed by PRGF in hen stromal cell cultures. Clinically, in PRGF-ICRS corneas at 7 days, there were more deposits with higher intensity than in ICRS group. Histologically, at day 2 there was less epithelial damage over the segment in the PRGF-ICRS group, corneal oedema around the segment disappeared earlier and, at day 7, there was also double the number of cells around the segment than in the ICRS group displaying different morphologies. The number of TUNEL-positive cells was statistically higher in the PRGF-ICRS group at 7 and 30 days, and the number of BrdU-positive cells was statistically higher at all analyzed times. However, there were no differences in the number of αSMA-positive cells at 30 days between both groups. Conclusions: The ICRS immersion in PRGF-Endoret prior and after to its corneal implantation, in an experimental animal model, enhances clinical deposits and histological cell turnover without increasing myofibroblast differentiation reducing stromal wound-healing time after surgery.

Escape rooms de Histología Especial como herramienta de mejora del aprendizaje.

2026-03-16T12:07:38Z

Nuestros alumnos son nativos digitales y las metodologías tradicionales ya no tienen en ellos el mismo impacto que tenían hace unos años. Por esta razón, las nuevas metodologías docentes están cobrando gran interés, destacando entre ellas la gamificación. Entre las diferentes actividades de gamificación destaca el desarrollo y realización de escape rooms (ERs, salas de escape) virtuales. Este trabajo muestra el resultado de la implantación, durante dos cursos académicos consecutivos, de ERs virtuales como herramienta de aprendizaje en la asignatura Histología Médica del Grado en Biomedicina y Terapias Avanzadas, con el objetivo principal de afianzar los conocimientos impartidos. La asignatura se divide en diferentes bloques temáticos y las ERs se basaron en los que presentan mayor dificultad de comprensión para nuestro alumnado. Del análisis de los resultados podemos concluir que la implantación de esta nueva metodología permite afianzar conocimientos teóricos y prácticos de la asignatura de una forma amena y motivadora y que su realización, de forma presencial, hace que nuestros alumnos integren los conocimientos impartidos de una manera continuada a lo largo del cuatrimestre, favoreciendo, por lo tanto, el proceso de aprendizaje y la superación de la asignatura de una manera más satisfactoria.

Photobonding of silk fibroin-based hydrogels to rabbit corneas

2026-03-16T12:45:03Z

Introduction: Corneal abrasions are common ocular injuries characterized by the loss of epithelial cells. Severe cases are often treated with amniotic membrane transplantation. However, as an allogenic tissue, it can trigger immune responses, it is scarce and costly, and may require suturing to the cornea. In this study, we propose and evaluate two silk fibroin-based hydrogels implanted in rabbit corneas with a sutureless photobonding technique as a surrogate for the amniotic membrane in corneal wound healing. Methods: Silk fibroin-based hydrogels were developed with polyethylene glycol (PEG) 300 or 3350. The hydrogels were stained with 0.01% Rose Bengal and photobonded to ex vivo de-epithelialized rabbit corneal strips using a custom-developed irradiation system (532 nm; 0.13 or 0.15 W/cm2 irradiance for 6.6 min). Bonding strength after 24 and 72 h under hydrated conditions was measured using a uniaxial stretcher, with five samples per experiment. An in vivo proof of concept study was also performed: hydrogels were implanted in four anesthetized rabbits that were euthanized immediately after photobonding for bonding assessment after 24 and 72 h in hydration. Two additional rabbits received in vivo implants, were clinically monitored for 15 and 30 days, and euthanized for histological evaluation. Results: Bonding strengths measured 24- or 72-h after irradiation at 0.13 or 0.15 W/cm2 of 532 nm light reached 2–3 N/cm2 for both types of Rose Bengal-stained hydrogels. In vivo bonding strength was consistent with the ex vivo results. At 15 and 30 days after the procedure, the corneas exhibited complete re-epithelialization beneath the hydrogel. Conclusion: Silk fibroin-based hydrogels can be successfully bonded to ex vivo rabbit corneas using a sutureless photobonding technique, achieving high bonding strength. The in vivo proof-of-concept study demonstrated the feasibility of the surgical procedure and confirmed corneal re-epithelialization.

The citrate transporters SLC13A5 and SLC25A1 elicit different metabolic responses and phenotypes in the mouse.

2026-03-13T09:29:54Z

Cytosolic citrate is imported from the mitochondria by SLC25A1, and from the extracellular milieu by SLC13A5. In the cytosol, citrate is used by ACLY to generate acetyl-CoA, which can then be exported to the endoplasmic reticulum (ER) by SLC33A1. Here, we report the generation of mice with systemic overexpression (sTg) of SLC25A1 or SLC13A5. Both animals displayed increased cytosolic levels of citrate and acetyl-CoA; however, SLC13A5 sTg mice developed a progeria-like phenotype with premature death, while SLC25A1 sTg mice did not. Analysis of the metabolic profile revealed widespread differences. Furthermore, SLC13A5 sTg mice displayed increased engagement of the ER acetylation machinery through SLC33A1, while SLC25A1 sTg mice did not. In conclusion, our findings point to different biological responses to SLC13A5- or SLC25A1-mediated import of citrate and suggest that the directionality of the citrate/acetyl-CoA pathway can transduce different signals.

The TP53 Arg72Pro polymorphism predicts visual and neurodegenerative outcomes in retinal detachment

2026-03-16T12:02:31Z

Retinal detachment (RD) separates the retina from the retinal epithelium, causing photoreceptor apoptosis and irreversible vision loss. Even with successful surgical reattachment, complete visual recovery is not guaranteed. The TP53 Arg72Pro polymorphism, implicated in apoptosis, has emerged as a potential predictor of RD outcomes. We investigated the impact of the Arg72Pro polymorphism on retinal neurodegeneration and functional recovery in patients. The underlying mechanisms were analyzed in a humanized TP53 Arg72Pro RD mouse model. In a cohort of 180 patients, carriers of the Pro allele exhibited decreased apoptotic gene expression and improved visual recovery. Complementary findings in mice revealed that the Pro variant preserved photoreceptor integrity and reduced apoptosis rates following RD. Our findings highlight the potential of this TP53 polymorphism as a biomarker for RD outcomes and a tool for tailoring therapies. This study underscores the importance of integrating genetic profiling into personalized medicine approaches to improve recovery of RD patients’ visual outcomes

The p.R321C mutation in the p62 protein is associated with abnormalities in the central nervous system

2026-04-10T05:51:51Z

SQSTM1/p62 has an essential role in autophagy, a catabolic pathway that is vital for maintaining cell homeostasis. p62 alterations have been observed in multiple pathological conditions, including neurodegenerative diseases and bone metabolism alterations. The p.R321C p62 protein mutation has been described in patients with amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Paget's disease of bone. In vitro studies associated the p62-321C variant with a blockade of autophagy and with the activation of the NF-kB pathway. We aimed to provide a deeper understating of the pathophysiological consequences of the p.R321C p62 mutation using a humanized mouse model. Micro-computed tomography, immunohistochemistry, and western blot analysis studied the functional consequences of the p. R321C p62 mutation. Statistical analyses were performed using SPSS software. The results showed that the p62-321C mice developed seizures after tactile-vestibular stimulation, probably associated with a blockage of the autophagy and NF-kB activation. Changes in expression of cFos and p62 were found in the amygdala, hypothalamic nuclei, and hippocampi nuclei. In addition, numerous degenerating motor neurons were observed in the spinal cord of the p62-321C mice. We report that the blockage of the autophagy, caused by p.R321C p62 mutation, is associated with abnormalities in the central nervous system, mainly seizures after tactile-vestibular stimulation and degeneration of the motor neurons of the spinal cord but not with bone abnormalities in a humanized mouse model

Association between genetic variants in CYP2E1 and CTRC genes and susceptibility to alcoholic pancreatitis: A systematic review and meta-analysis

2026-04-09T10:56:28Z

Background: Genetic predisposition plays an important role in the development of alcoholic pancreatitis (AP), with previous studies suggesting that genetics variants in certain genes, such asCYP2E1 and CTRC, partially explain individual susceptibility to this disease. Therefore, the aim of this work was to conduct a systematic review and meta-analysis of existing studies that analyzed how polymorphisms within CYP2E1 and CTRC genes influence the risk of AP. Material and methods: We performed a systematic review of studies that analyzed the genotype distribution of CYP2E1 and CTRC allelic variants among patients with AP and a group of controls. A meta-analysis was conducted using a random effects model. Odds ratios (ORs) and their confidence intervals (CIs) were calculated. Results: The T allele of theCTRC 180 C > T variant was significantly more prevalent among patients with AP compared to all controls (OR = 1.79, 95% CI = 1.43-2.24; P < 0.00001) and healthy subjects (OR = 1.84, 95% CI = 1.46-2.31; P < 0.00001). The Trp variant of CTRC Arg254Trp polymorphism was also more prevalent in patients with AP; however, these results were not significant after excluding one study. We found no clear evidence that CYP2E1-DraI or of CYP2E1-RsaI/PstI polymorphisms modulate the risk of developing AP. Conclusions: Our meta-analysis supports that the T allele ofCTRC 180C > T polymorphisms modulates the risk of alcoholic pancreatitis. No clear evidence was found for the remaining SNPs being associated with this disease.

Sexual activity before exercise influences physiological response and sports performance in high-level trained men athletes

2026-03-13T11:30:13Z

Background The influence of sexual activity prior to exercise on athletic performance remains controversial. While pre-competition abstinence is commonly advised, scientific evidence on its physiological impact is limited and inconsistent. Methods A randomized crossover study was conducted in 21 well-trained male athletes (age 22 ± 1 y) to compare the acute effects of masturbation-induced orgasm versus sexual abstinence performed 30 min before testing. Each participant completed an incremental cycling test and an isometric handgrip strength test under both conditions. Blood samples were analyzed for muscle damage (CK, LDH, Mb), inflammatory (CRP, IL-6), and hormonal (testosterone, cortisol, LH) markers. Results Compared with abstinence, the post-masturbation condition resulted in a longer exercise duration (+3.2%, p < 0.01) and higher heart rate (p < 0.001), accompanied by a small increase in mean handgrip strength (p < 0.05). Lower plasma LDH levels (p < 0.001) indicated reduced muscle stress. Testosterone and cortisol concentrations were significantly higher (both p < 0.001), whereas inflammatory markers (CRP, IL-6) showed no significant change. Conclusions Masturbation 30 min before exercise elicited mild sympathetic and hormonal activation without detrimental effects on performance or muscle damage. These findings suggest that pre-exercise sexual activity does not impair athletic capacity in trained men, challenging the long-standing myth of mandatory abstinence before competition.

RESULTADOS DE LAS ENCUESTAS DE VALORACIÓN DE LA ESCAPE ROOM “The Genetic Room Reloaded” - PID 24-25_004_Anexo_2

2025-12-19T13:46:57Z

Resultados de la encuesta proporcionada a los estudiantes de 2º Curso de BMyTA: Rol: Participantes en “The Genetic Room Reloaded"

Resultados de encuesta de satisfacción de los estudiantes de 3º BMyTA - PID 24-25_004_Anexo_1

2025-12-19T13:47:26Z

Resultados de la encuesta proporcionada a los estudiantes de 3º Curso de BMyTA: Rol: Diseñadores y máster del “The Genetic Room Reloaded.

Pancreatic β-cell-specific deletion of insulin-degrading enzyme leads to dysregulated insulin secretion and β-cell functional immaturity

2025-02-18T12:10:17Z

Inhibition of insulin-degrading enzyme (IDE) has been proposed as a possible therapeutic target for type 2 diabetes treatment. However, many aspects of IDE's role in glucose homeostasis need to be clarified. In light of this, new preclinical models are required to elucidate the specific role of this protease in the main tissues related to insulin handling. To address this, here we generated a novel line of mice with selective deletion of the Ide gene within pancreatic beta-cells, B-IDE-KO mice, which have been characterized in terms of multiple metabolic end points, including blood glucose, plasma C-peptide, and intraperitoneal glucose tolerance tests. In addition, glucose-stimulated insulin secretion was quantified in isolated pancreatic islets and beta-cell differentiation markers and insulin secretion machinery were characterized by RT-PCR. Additionally, IDE was genetically and pharmacologically inhibited in INS-1E cells and rodent and human islets, and insulin secretion was assessed. Our results show that, in vivo, life-long deletion of IDE from beta-cells results in increased plasma C-peptide levels. Corroborating these findings, isolated islets from B-IDE-KO mice showed constitutive insulin secretion, a hallmark of beta-cell functional immaturity. Unexpectedly, we found 60% increase in Glut1 (a high-affinity/low-Km glucose transporter), suggesting increased glucose transport into the beta-cell at low glucose levels, which may be related to constitutive insulin secretion. In parallel, IDE inhibition in INS-1E and islet cells resulted in impaired insulin secretion after glucose challenge. We conclude that IDE is required for glucose-stimulated insulin secretion. When IDE is inhibited, insulin secretion machinery is perturbed, causing either inhibition of insulin release at high glucose concentrations or constitutive secretion.

Impact of discontinuing non-pharmacological interventions on cognitive impairment in dementia patients by COVID-19 lockdown. A pilot observational, longitudinal, retrospective study carried out in an adult day center in Spain during the COVID-19 pandemic

2026-03-19T08:39:59Z

ackground: The lockdown imposed during the COVID-19 pandemic led to social isolation and prevented patients with dementia from receiving a suite of non-pharmacological interventions (NPIs) that prevent cognitive decline. This discontinuation of NPIs could substantially affect the mental health status of people with dementia in social care settings, such as adult day care centers (ADCs). Propose: The study aimed to evaluate the effects of the COVID-19 lockdown on mental health and cognitive impairment in patients with dementia who could not attend their usual ADCs and did not receive our NPIs, based on World Health Organization (WHO) Guidelines. Methods: Observational, longitudinal, retrospective study carried out in an adult day center in Spain and reported it in accordance with the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) statement. Cognitive status was assessed using the Mini-Mental State Examination (MMSE) in 80 patients attending the ADC of the "Leonese Association of Dementia Patients" (León, Spain), who had been evaluated with this instrument before the COVID-19 lockdown. Results: We observed a 0.4-point decrease in MMSE score/month (IQR = 1.4) during lockdown versus a 0.1-point decrease/month (IQR = 0.3) before this period (p = 0.038). Notably, this translated to >10-point decreases in MMSE score/year in 33.8% of participants during lockdown versus 5.5% earlier (p < 0.001). No statistically significant associations (p < 0.05) were found between the individual characteristics of the caregivers and the occurrence of the event. Conclusion: The reported declines in MMSE scores reveal a significant acceleration of cognitive decline during the period of inactivity. This could suggest that our NPIs, focused on slowing cognitive decline, are beneficial and, therefore, necessary in patients with dementia.

How hormones, vertical jump and perceived exertion change in clutch time. A season case study of an amateur basketball team

2026-04-06T08:44:24Z

Basketball clutch time is defined as minutes when the scoring margin is within 5 points with five or fewer minutes remaining in a game. Our aims were to explore the relations and to compare testosterone and cortisol behaviours, vertical jump (CMJ) and perceived exertion (RPE) between clutch time games (CT) and non-clutch time games (N-CT); during a season in an amateur male team (24.02 ± 3.36 years). Data was collected at 22 games considering CT (n = 8) or N-CT (n = 14) depending on the scoring margin with five or fewer minutes. A total of 120 player cases who participated in the last 5 min of each game (CT, n = 48; N-CT, n = 72) were analysed using a mixed linear model for repeated measures to compare the CT and N-CT variations. The main results were Cortisol, CMJ and RPE means turned out to be higher in CT, but relevant differences were only identified for RPE (ES = 0.69). Findings suggested that clutch performance was often viewed through players’ subjective parameters. Consequently, we recommend that both players and coaches consider it for CT performance. In addition, we extend current basketball CT indicator knowledge opening future research and applied practice.

Nutrition-related mobile apps in the Spanish app stores: quality and content analysis

2025-09-03T10:09:36Z

Background: Mobile apps represent accessible and cost-effective tools to improve nutrition and prevent chronic diseases. However, most of these apps have been characterized as having limited functionality, raising concerns about their effectiveness, acceptability, and efficacy. Objective: The aims of the study were to assess the quality of popular nutrition-related app platforms in Spain and to describe their characteristics and functionalities. Methods: We screened apps providing information on dietary advice, food advice, and nutritional content in the Apple App Store and Google Play Store in Spain from March 2 to March 16, 2024. Apps with a star rating of ≥4 (of 5 stars), those available in Spanish, those that were free of charge, those last updated after January 2022, those with >500 reviews, and those with >500,000 downloads were included. The quality of apps was assessed using the user version of the Mobile App Rating Scale (uMARS). General characteristics and nutritional, health, and market-related functionalities of the nutrition-related apps were described. Correlations among total and uMARS sections, star ratings, and number of reviews and downloads were evaluated. Results: Among the 1460 apps identified in the search, 42 apps met the criteria. The majority of these (n=20, 48%) aimed at recording and analyzing food intake, followed by those providing nutritional plans or diets (n=9, 21%), advising on healthy habits (n=7, 17%), and offering recipes (n=6, 14%). The most prevalent nutritional functionalities offered were recording and monitoring body measurements (n=30, 71%), food tracking (n=26, 62%), and dietary analysis (n=25, 60%), whereas nutrition education was less common (n=16, 38%). Among market-related functionalities, advertisements were the most common among the study apps (n=30, 71%), followed by the option of sharing on social media (n=29, 69%) and customizable reminders (n=26, 62%). Sharing the recorded information in the app with health professionals was infrequent (n=1, 2%). The mean (SD) total uMARS score (maximum 5 points) was 3.78 (0.35), while the mean (SD) uMARS scores for functionality, aesthetics, engagement, and information were 4.21 (0.38), 3.94 (0.54), 3.51 (0.46), and 3.48 (0.44), respectively. Lower mean scores were observed for the subjective quality (mean 2.65, SD 0.56) and perceived impact (mean 3.06, SD 0.67). Moderate to strong positive significant correlations were mostly observed between total uMARS and section-specific uMARS scores, while the correlations between the uMARS section scores were mostly moderate positive. Total uMARS scores were very weakly correlated with user rating, number of reviews, and number of downloads. Conclusions: The quality of popular nutrition-related app platforms in Spain was acceptable, with observed remarkable differences between sections. The majority of the apps were appealing due to their user-friendly interfaces. Only a few apps, however, provided dietary structure analysis or nutritional education. Further research is needed to assess the long-term impact of these apps on users.

Architectural Arrangement of Neurons as Part of the Functional Unit of the Central Nervous System

2025-01-14T20:04:03Z

La comprensión de las relaciones estructurales celulares en el tejido cerebral humano permitirá una mejor apreciación de la importancia funcional. Un modelo de la unidad funcional reúne los tipos de células importantes con una mejor visualización de las relaciones. Si bien muchas investigaciones evalúan las relaciones metabólicas de las células cerebrales, una visualización de las relaciones estructurales mejora nuestra comprensión de otras maneras que conducirán a futuros avances en el Alzheimer y otras enfermedades neurodegenerativas.