Role of miRNAs in the enterocolitis syndrome due to food proteins and their potential as diagnostic and predictive targets.
Authorship
A.A.M.
Master in Biomedical Research
A.A.M.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Food protein-induced enterocolitis syndrome (FPIES) is a potentially severe non-IgE-mediated food allergy whose pathophysiology is still poorly understood, mainly affecting young children. Symptoms may be mistaken for sepsis or acute gastroenteritis, which may lead to ineffective, costly or even unnecessary invasive interventions. Expression profiles of miRNAs could be useful in identifying biomarkers associated with this disease. In this study, blood samples were taken from 29 patients with suspected FPIES who had a moderate or severe reaction during the trigger food challenge test. Expression profiles of miRNAs were analysed at three time points: before the challenge test (TP1), during the reaction (TP2) and four hours later (TP3) using an nCounter NanoString miRNA panel. Longitudinal analysis revealed a heterogeneous response at baseline that evolved into a more consistent pattern at TP3, indicating that it is dynamic and evolves over time. A total of 11 miRNAs (9 up-regulated and 2 down-regulated) were identified as showing the greatest changes in expression. The study of the molecular pathways involved revealed that these miRNAs play an important role in the TGF-beta signalling pathway and in the differentiation of T lymphocytes during the allergic reaction to FPIES. This work has allowed us to identify miRNAs that undergo significant changes in their expression throughout the reaction, with the potential to be used as biomarkers to help differentiate FPIES from other pathologies. Furthermore, the analysis of the pathways involved offers new opportunities to improve the diagnosis and treatment of this disease.
Food protein-induced enterocolitis syndrome (FPIES) is a potentially severe non-IgE-mediated food allergy whose pathophysiology is still poorly understood, mainly affecting young children. Symptoms may be mistaken for sepsis or acute gastroenteritis, which may lead to ineffective, costly or even unnecessary invasive interventions. Expression profiles of miRNAs could be useful in identifying biomarkers associated with this disease. In this study, blood samples were taken from 29 patients with suspected FPIES who had a moderate or severe reaction during the trigger food challenge test. Expression profiles of miRNAs were analysed at three time points: before the challenge test (TP1), during the reaction (TP2) and four hours later (TP3) using an nCounter NanoString miRNA panel. Longitudinal analysis revealed a heterogeneous response at baseline that evolved into a more consistent pattern at TP3, indicating that it is dynamic and evolves over time. A total of 11 miRNAs (9 up-regulated and 2 down-regulated) were identified as showing the greatest changes in expression. The study of the molecular pathways involved revealed that these miRNAs play an important role in the TGF-beta signalling pathway and in the differentiation of T lymphocytes during the allergic reaction to FPIES. This work has allowed us to identify miRNAs that undergo significant changes in their expression throughout the reaction, with the potential to be used as biomarkers to help differentiate FPIES from other pathologies. Furthermore, the analysis of the pathways involved offers new opportunities to improve the diagnosis and treatment of this disease.
Direction
SALAS ELLACURIAGA, ANTONIO (Tutorships)
GOMEZ CARBALLA, ALBERTO (Co-tutorships)
SALAS ELLACURIAGA, ANTONIO (Tutorships)
GOMEZ CARBALLA, ALBERTO (Co-tutorships)
Court
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
Monoclonal antibody of pTau as a therapy in Alzheimer’s disease.
Authorship
A.A.T.
Master in Biomedical Research
A.A.T.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Alzheimer’s disease is a neurodegenerative disorder that affects millions of people worldwide. Moreover, the clinical consequences of this condition represent one of the leading causes of mortality and disability in developed countries. It is important to highlight that Alzheimer’s disease is characterized by the abnormal accumulation of two key proteins that trigger brain damage and progressive cognitive decline: Bamyloid peptide (AB) and Tau protein. Both proteins are known to form toxic aggregates that initiate a cascade of severe molecular and cellular alterations. At the cellular level, dysfunction is observed in the endocytic and autophagic pathways, along with increased levels of reactive oxygen species (ROS), plasma membrane alterations, dysregulation of membrane potential, and damage to various organelles such as mitochondria and the endoplasmic reticulum. On the other hand, at the extracellular level, there is an exacerbated activation of the inflammatory response and disturbances in the concentration of several neurotransmitters, as a result of damage to multiple brain regions. Tau protein also exhibits complex physiological functions: it interacts with microtubule-associated proteins, synaptic elements, as well as DNA and RNA. These interactions are modulated by post-translational modifications, which are crucial both for its normal function and its dysfunction in the pathological context. Additionally, Tau displays prion-like properties, allowing it to propagate pathologically between neurons and thereby contribute to disease progression. Currently, the treatments available for Alzheimer’s disease are purely symptomatic, based on acetylcholinesterase (AChE) inhibitors or NmethylDaspartate (NMDA) receptor antagonists. However, in recent years, new therapeutic strategies based on monoclonal antibodies have begun to emerge, offering a promising alternative. In this context, the NEURAL group at IDIS, as part of the development of a European project coordinated by Dr. Tomás Sobrino, has developed the B6 monoclonal antibody, specifically targeting three phosphorylation sites of the Tau protein. This antibody has been evaluated in murine models of Alzheimer’s disease, demonstrating its clinical potential. To this end, various biomarkers of damage and neurodegeneration were analysed using advanced proteomic and analytical techniques, with the aim of characterizing the molecular and functional therapeutic effects of B6.
Alzheimer’s disease is a neurodegenerative disorder that affects millions of people worldwide. Moreover, the clinical consequences of this condition represent one of the leading causes of mortality and disability in developed countries. It is important to highlight that Alzheimer’s disease is characterized by the abnormal accumulation of two key proteins that trigger brain damage and progressive cognitive decline: Bamyloid peptide (AB) and Tau protein. Both proteins are known to form toxic aggregates that initiate a cascade of severe molecular and cellular alterations. At the cellular level, dysfunction is observed in the endocytic and autophagic pathways, along with increased levels of reactive oxygen species (ROS), plasma membrane alterations, dysregulation of membrane potential, and damage to various organelles such as mitochondria and the endoplasmic reticulum. On the other hand, at the extracellular level, there is an exacerbated activation of the inflammatory response and disturbances in the concentration of several neurotransmitters, as a result of damage to multiple brain regions. Tau protein also exhibits complex physiological functions: it interacts with microtubule-associated proteins, synaptic elements, as well as DNA and RNA. These interactions are modulated by post-translational modifications, which are crucial both for its normal function and its dysfunction in the pathological context. Additionally, Tau displays prion-like properties, allowing it to propagate pathologically between neurons and thereby contribute to disease progression. Currently, the treatments available for Alzheimer’s disease are purely symptomatic, based on acetylcholinesterase (AChE) inhibitors or NmethylDaspartate (NMDA) receptor antagonists. However, in recent years, new therapeutic strategies based on monoclonal antibodies have begun to emerge, offering a promising alternative. In this context, the NEURAL group at IDIS, as part of the development of a European project coordinated by Dr. Tomás Sobrino, has developed the B6 monoclonal antibody, specifically targeting three phosphorylation sites of the Tau protein. This antibody has been evaluated in murine models of Alzheimer’s disease, demonstrating its clinical potential. To this end, various biomarkers of damage and neurodegeneration were analysed using advanced proteomic and analytical techniques, with the aim of characterizing the molecular and functional therapeutic effects of B6.
Direction
MARTIN CORA, FRANCISCO JAVIER (Tutorships)
Sobrino Moreiras, Tomás (Co-tutorships)
Ouro Villasante, Alberto (Co-tutorships)
MARTIN CORA, FRANCISCO JAVIER (Tutorships)
Sobrino Moreiras, Tomás (Co-tutorships)
Ouro Villasante, Alberto (Co-tutorships)
Court
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
The role of ATF4 and other stress response regulators in mitochondrial disease
Authorship
I.B.F.
Master in Biomedical Research
I.B.F.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Mitochondrial diseases (MDs) are metabolic disorders that affect 1 in 5000 adults and can be caused by both defects in mitochondrial and nuclear DNA. A single cell can harbour several copies of mitochondrial DNA (mtDNA) leading to a coexistence of mutant and wild-type molecules, a phenomenon known as heteroplasmy. Although different factors, including nutrient deprivation, have been proposed to modulate mutant load, the molecular mechanisms underlying their effect remain poorly understood. Moreover, as the Integrated Stress Response (ISR) is commonly activated in MD models and under nutrient-restricted conditions, its main effector, the activator factor 4 (ATF4), was proposed as a potential modulator. Here, by using human cell lines carrying the m.3243AG and m.8344AG mtDNA mutations in heteroplasmy, we found that glucose and glutamine restriction modulate heteroplasmy in a mutation-specific manner. These changes were accompanied by a shift from fragmented to fused mitochondrial morphology together with a partial rescue of the mitochondrial protein levels. Despite these findings, pharmacological and genetic manipulation of ATF4 did not significantly alter mutant load, suggesting that ATF4 is not a central regulator of heteroplasmy, or the mitochondrial network and/or protein levels under these conditions and other processes like the mitochondrial network dynamics itself might be playing a key role. Even further analysis is needed to fully understand the mechanisms underlying the partial recovery, altogether, our findings reveal a complex relationship between nutrient availability, mitochondrial dynamics, and genotype-specific responses, and suggest new avenues for metabolic interventions in mitochondrial diseases that might fall beyond the activation of ATF4 and the ISR.
Mitochondrial diseases (MDs) are metabolic disorders that affect 1 in 5000 adults and can be caused by both defects in mitochondrial and nuclear DNA. A single cell can harbour several copies of mitochondrial DNA (mtDNA) leading to a coexistence of mutant and wild-type molecules, a phenomenon known as heteroplasmy. Although different factors, including nutrient deprivation, have been proposed to modulate mutant load, the molecular mechanisms underlying their effect remain poorly understood. Moreover, as the Integrated Stress Response (ISR) is commonly activated in MD models and under nutrient-restricted conditions, its main effector, the activator factor 4 (ATF4), was proposed as a potential modulator. Here, by using human cell lines carrying the m.3243AG and m.8344AG mtDNA mutations in heteroplasmy, we found that glucose and glutamine restriction modulate heteroplasmy in a mutation-specific manner. These changes were accompanied by a shift from fragmented to fused mitochondrial morphology together with a partial rescue of the mitochondrial protein levels. Despite these findings, pharmacological and genetic manipulation of ATF4 did not significantly alter mutant load, suggesting that ATF4 is not a central regulator of heteroplasmy, or the mitochondrial network and/or protein levels under these conditions and other processes like the mitochondrial network dynamics itself might be playing a key role. Even further analysis is needed to fully understand the mechanisms underlying the partial recovery, altogether, our findings reveal a complex relationship between nutrient availability, mitochondrial dynamics, and genotype-specific responses, and suggest new avenues for metabolic interventions in mitochondrial diseases that might fall beyond the activation of ATF4 and the ISR.
Direction
GOMEZ DURAN, AURORA (Tutorships)
GOMEZ DURAN, AURORA (Tutorships)
Court
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
Development of nanoencapsulated systems for its use in targeted cancer treatment
Authorship
A.C.C.
Master in Biomedical Research
A.C.C.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Cancer is considered a major societal and public health issue, accounting for about 9.7 million deaths worldwide in 2022. A key factor contributing to this high mortality rate is the late stage at which many cancers are diagnosed, often after metastasis to distinct organs has occurred. Conventional and combination treatments often have several side effects and a poor quality of life for patients. Photodynamic Therapy (PDT) using photosensitizer-loaded nanoemulsions (NEs) has emerged as an alternative approach for selectively targeting cancer cells while minimizing systemic toxicity. In this context, we propose the formulation of oil-in-water NEs using as hydrophobic photosensitizer verteporfin (VP), which is activated under near-infrared (NIR) light exposure, causing cell death, mainly due to the release of intracellular reactive oxygen species (ROS). Four different NEs were developed based on their fatty acid core composition: palmitoleic acid (POA), monounsaturated, and palmitic acid (PA), saturated; and on the presence of encapsulated PV. As a result, PA, VPA, POA and VPOA-NEs were generated. The VP was successfully encapsulated at various concentrations and the encapsulation efficiency, around 90%, was obtained through spectrophotometry. Physicochemical characterization was performed using: Transmission Electron Microscopy, Nanoparticle Tracking Analysis, and Dynamic Light Scattering, to evaluate particle concentration, size, polydispersity index, and surface charge. In vitro assays in SKOV-3 (ovarian) and A549 (lung) cancer cell lines showed efficient VP-NEs internalization and light-dependent cytotoxicity upon NIR activation, implying their high therapeutic potential.
Cancer is considered a major societal and public health issue, accounting for about 9.7 million deaths worldwide in 2022. A key factor contributing to this high mortality rate is the late stage at which many cancers are diagnosed, often after metastasis to distinct organs has occurred. Conventional and combination treatments often have several side effects and a poor quality of life for patients. Photodynamic Therapy (PDT) using photosensitizer-loaded nanoemulsions (NEs) has emerged as an alternative approach for selectively targeting cancer cells while minimizing systemic toxicity. In this context, we propose the formulation of oil-in-water NEs using as hydrophobic photosensitizer verteporfin (VP), which is activated under near-infrared (NIR) light exposure, causing cell death, mainly due to the release of intracellular reactive oxygen species (ROS). Four different NEs were developed based on their fatty acid core composition: palmitoleic acid (POA), monounsaturated, and palmitic acid (PA), saturated; and on the presence of encapsulated PV. As a result, PA, VPA, POA and VPOA-NEs were generated. The VP was successfully encapsulated at various concentrations and the encapsulation efficiency, around 90%, was obtained through spectrophotometry. Physicochemical characterization was performed using: Transmission Electron Microscopy, Nanoparticle Tracking Analysis, and Dynamic Light Scattering, to evaluate particle concentration, size, polydispersity index, and surface charge. In vitro assays in SKOV-3 (ovarian) and A549 (lung) cancer cell lines showed efficient VP-NEs internalization and light-dependent cytotoxicity upon NIR activation, implying their high therapeutic potential.
Direction
LOPEZ LOPEZ, RAFAEL (Tutorships)
DAVILA IBAÑEZ, ANA BELEN (Co-tutorships)
LOPEZ LOPEZ, RAFAEL (Tutorships)
DAVILA IBAÑEZ, ANA BELEN (Co-tutorships)
Court
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
Optimization of an Intein-Based Protein Purification System for the Production of Rad51 and Rad54
Authorship
A.C.A.
Master in Biomedical Research
A.C.A.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Affinity chromatography is a fundamental tool in protein purification due to its high specificity, efficiency, and ability to preserve biological activity. The IMPACT purification system (Intein Mediated Purification with an Affinity Chitin-binding Tag) based on inteins from New England Biolabs, using vectors such as pTXB1, takes advantage of the self-cleaving activity of inteins to separate the target protein from the affinity tag. This innovative system offers several significant advantages in the production and purification of recombinant proteins. Firstly, it eliminates the need for proteases to release the protein of interest, enabling purification through a single chromatographic step. Additionally, it allows the recovery of the target protein without the addition of extra amino acid residues from the expression vector. Finally, it offers flexibility to isolate proteins with or without an N-terminal methionine residue, depending on experimental or functional requirements. However, a potential drawback is the low binding capacity of chitin resins (approximately 2 mg/mL). In this work, we aimed to adapt these vectors to express polyhistidine tags so that proteins can be captured not only using chitin columns but also through an IMAC (Immobilized Metal Affinity Chromatography) system such as Ni-NTA (nickel bound to nitrilotriacetic acid). To achieve this, we modified the pTXB1 vector by adding histidine tags to enhance the initial capture of the protein of interest, leveraging the advantages provided by the intein-based system. From this point, it would be possible to perform the capture using Ni-NTA resin and compare the purification efficiency with existing protocols.
Affinity chromatography is a fundamental tool in protein purification due to its high specificity, efficiency, and ability to preserve biological activity. The IMPACT purification system (Intein Mediated Purification with an Affinity Chitin-binding Tag) based on inteins from New England Biolabs, using vectors such as pTXB1, takes advantage of the self-cleaving activity of inteins to separate the target protein from the affinity tag. This innovative system offers several significant advantages in the production and purification of recombinant proteins. Firstly, it eliminates the need for proteases to release the protein of interest, enabling purification through a single chromatographic step. Additionally, it allows the recovery of the target protein without the addition of extra amino acid residues from the expression vector. Finally, it offers flexibility to isolate proteins with or without an N-terminal methionine residue, depending on experimental or functional requirements. However, a potential drawback is the low binding capacity of chitin resins (approximately 2 mg/mL). In this work, we aimed to adapt these vectors to express polyhistidine tags so that proteins can be captured not only using chitin columns but also through an IMAC (Immobilized Metal Affinity Chromatography) system such as Ni-NTA (nickel bound to nitrilotriacetic acid). To achieve this, we modified the pTXB1 vector by adding histidine tags to enhance the initial capture of the protein of interest, leveraging the advantages provided by the intein-based system. From this point, it would be possible to perform the capture using Ni-NTA resin and compare the purification efficiency with existing protocols.
Direction
González Blanco, Miguel (Tutorships)
González Blanco, Miguel (Tutorships)
Court
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
LAREU HUIDOBRO, MARIA VICTORIA (Chairman)
ALVAREZ CASTRO, EZEQUIEL (Secretary)
GARCIA ALONSO, ANGEL (Member)
Characterization of the Role of PI3k Beta And Delta Isoforms in Platelet Activation
Authorship
F.A.C.N.
Master in Biomedical Research
F.A.C.N.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Platelet activation, essential for hemostasis and thrombosis, is regulated by several intracellular pathways, including phosphatidylinositol 3-kinase (PI3K). This study examined the differential role of PI3K beta and PI3K delta isoforms in platelet activation induced by the collagen receptor Glycoprotein VI (GPVI). A whole blood microfluidics model was used to evaluate the effect of specific inhibitors on activation and thrombus formation. A mechanistic western blot analysis of intracellular Akt/GSK3b/PTEN signaling after activation with collagen-related peptide (CRP) and inhibitors was performed. The results showed that all inhibitors tested by microfluidics were able to significantly decrease P-selectin expression, fibrinogen binding, and phosphatidylserine exposure, while an effect on thrombus formation was only evident against PI3K delta inhibition with idelalisib and GSK2636771 (GSK3b). On the other hand, the PI3K delta inhibitors, idelalisib and AMG-319, showed a consistent inhibition of Akt, and in the case of AMG-319 also of GSK3b, supporting its effect on the classical PI3K/Akt pathway. Regarding PI3K beta inhibitors, both TGX-221 and GSK2636771 managed to reduce GSK3b phosphorylation, although their effect on Akt was less uniform. PTEN phosphorylation levels were not affected by experimental conditions. These findings suggest that both PI3K beta and PI3K delta participate in platelet activation, with the role of the delta isoform being more relevant than described to date, and therefore could represent a more specific antithrombotic therapeutic strategy.
Platelet activation, essential for hemostasis and thrombosis, is regulated by several intracellular pathways, including phosphatidylinositol 3-kinase (PI3K). This study examined the differential role of PI3K beta and PI3K delta isoforms in platelet activation induced by the collagen receptor Glycoprotein VI (GPVI). A whole blood microfluidics model was used to evaluate the effect of specific inhibitors on activation and thrombus formation. A mechanistic western blot analysis of intracellular Akt/GSK3b/PTEN signaling after activation with collagen-related peptide (CRP) and inhibitors was performed. The results showed that all inhibitors tested by microfluidics were able to significantly decrease P-selectin expression, fibrinogen binding, and phosphatidylserine exposure, while an effect on thrombus formation was only evident against PI3K delta inhibition with idelalisib and GSK2636771 (GSK3b). On the other hand, the PI3K delta inhibitors, idelalisib and AMG-319, showed a consistent inhibition of Akt, and in the case of AMG-319 also of GSK3b, supporting its effect on the classical PI3K/Akt pathway. Regarding PI3K beta inhibitors, both TGX-221 and GSK2636771 managed to reduce GSK3b phosphorylation, although their effect on Akt was less uniform. PTEN phosphorylation levels were not affected by experimental conditions. These findings suggest that both PI3K beta and PI3K delta participate in platelet activation, with the role of the delta isoform being more relevant than described to date, and therefore could represent a more specific antithrombotic therapeutic strategy.
Direction
GARCIA ALONSO, ANGEL (Tutorships)
GARCIA ALONSO, ANGEL (Tutorships)
Court
VIDAL FIGUEROA, ANXO (Chairman)
TOVAR CARRO, SULAY AMPARO (Secretary)
MARTIN CORA, FRANCISCO JAVIER (Member)
VIDAL FIGUEROA, ANXO (Chairman)
TOVAR CARRO, SULAY AMPARO (Secretary)
MARTIN CORA, FRANCISCO JAVIER (Member)
Inflammation and cardiac pathology in Duchenne muscular dystrophy: effect of the peptide obestatin
Authorship
L.D.C.
Master in Biomedical Research
L.D.C.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Duchenne muscular dystrophy (DMD) is an X-linked, recessively inherited, neuromuscular disease affecting 1 in 5000 male births. It is a lethal disease, currently incurable and caused by a mutation in the DMD gene, which triggers the absence of the dystrophin protein. The disappearance of this protein, which is essential for the stability of muscle cells, leads to progressive muscle weakness. One of the signs of the disease is dilated cardiomyopathy, which is present in almost all elderly patients and is now the leading cause of premature death. It is characterised by inflammation of the heart muscle, dilatation and thinning of the wall, impaired homeostasis and cell death, chronic fibrosis and loss of contractile capacity. A multidisciplinary approach is essential for treatment and symptom reduction. The obestatin/GPR39 system has shown positive effects on skeletal muscle, such as increased muscle strength, reduced fibrosis and overall improved phenotype in animal models of DMD. The main objective of this work is to elucidate the molecular and inflammatory mechanisms underlying the cardiac pathology associated with DMD at late ages, in order to evaluate the possible effect of obestatin peptide administration on late dystrophic cardiac muscle. Immunoblot and quantitative RT-PCR results revealed alterations in anabolic and catabolic pathways as well as in mitochondrial homeostasis and inflammatory processes in the heart muscle of the mdx animal model. Obestatin treatment restored anabolic pathways and exerted a protective role against fibrosis and cell death. Microarray analysis of the inflammatory profile reveals an anti-inflammatory environment in the late heart muscle of mdx animals, reversed by obestatin treatment, which positively modulates different pro-inflammatory markers.
Duchenne muscular dystrophy (DMD) is an X-linked, recessively inherited, neuromuscular disease affecting 1 in 5000 male births. It is a lethal disease, currently incurable and caused by a mutation in the DMD gene, which triggers the absence of the dystrophin protein. The disappearance of this protein, which is essential for the stability of muscle cells, leads to progressive muscle weakness. One of the signs of the disease is dilated cardiomyopathy, which is present in almost all elderly patients and is now the leading cause of premature death. It is characterised by inflammation of the heart muscle, dilatation and thinning of the wall, impaired homeostasis and cell death, chronic fibrosis and loss of contractile capacity. A multidisciplinary approach is essential for treatment and symptom reduction. The obestatin/GPR39 system has shown positive effects on skeletal muscle, such as increased muscle strength, reduced fibrosis and overall improved phenotype in animal models of DMD. The main objective of this work is to elucidate the molecular and inflammatory mechanisms underlying the cardiac pathology associated with DMD at late ages, in order to evaluate the possible effect of obestatin peptide administration on late dystrophic cardiac muscle. Immunoblot and quantitative RT-PCR results revealed alterations in anabolic and catabolic pathways as well as in mitochondrial homeostasis and inflammatory processes in the heart muscle of the mdx animal model. Obestatin treatment restored anabolic pathways and exerted a protective role against fibrosis and cell death. Microarray analysis of the inflammatory profile reveals an anti-inflammatory environment in the late heart muscle of mdx animals, reversed by obestatin treatment, which positively modulates different pro-inflammatory markers.
Direction
CASABIELL PINTOS, JESÚS ANTONIO (Tutorships)
Santos Zas, Icía (Co-tutorships)
CASABIELL PINTOS, JESÚS ANTONIO (Tutorships)
Santos Zas, Icía (Co-tutorships)
Court
VIDAL FIGUEROA, ANXO (Chairman)
TOVAR CARRO, SULAY AMPARO (Secretary)
MARTIN CORA, FRANCISCO JAVIER (Member)
VIDAL FIGUEROA, ANXO (Chairman)
TOVAR CARRO, SULAY AMPARO (Secretary)
MARTIN CORA, FRANCISCO JAVIER (Member)
Influence of the production system on the quality and nutritional composition of cow's milk
Authorship
R.D.M.
Master in Genetic, Nutritional and Environmental Determinants concerning Growth and Development-NUTRENVIGEN G+D Factors
R.D.M.
Master in Genetic, Nutritional and Environmental Determinants concerning Growth and Development-NUTRENVIGEN G+D Factors
Defense date
07.17.2025 09:00
07.17.2025 09:00
Summary
Milk has a high nutritional value in the human diet, determined by its varied chemical composition, and is especially essential for children nutrition. Several factors can modify its composition and quality, potentially affecting human health. The main objective of this study was to analyze the quality and nutritional composition of raw cow’s milk according to the production system. To this end, samples from four different production types were collected and analyzed for their fatty acids, minerals and microbiological composition. The data were subjected to statistical analysis using Prism software. The results showed a higher presence of essential polyunsaturated fatty acids in organic milk, suggesting a more favorable nutritional profile for children diets. Intensively produced milk presented higher amounts of calcium and iodine, key minerals for child development, while organic milk had a higher sodium concentration, the intake of which should be limited during childhood. From a microbiological perspective, aerobic bacteria and enterococci were found in greater amounts in pasture-based milk. These findings highlight the influence of production systems on the quality and nutritional composition of raw cow’s milk.
Milk has a high nutritional value in the human diet, determined by its varied chemical composition, and is especially essential for children nutrition. Several factors can modify its composition and quality, potentially affecting human health. The main objective of this study was to analyze the quality and nutritional composition of raw cow’s milk according to the production system. To this end, samples from four different production types were collected and analyzed for their fatty acids, minerals and microbiological composition. The data were subjected to statistical analysis using Prism software. The results showed a higher presence of essential polyunsaturated fatty acids in organic milk, suggesting a more favorable nutritional profile for children diets. Intensively produced milk presented higher amounts of calcium and iodine, key minerals for child development, while organic milk had a higher sodium concentration, the intake of which should be limited during childhood. From a microbiological perspective, aerobic bacteria and enterococci were found in greater amounts in pasture-based milk. These findings highlight the influence of production systems on the quality and nutritional composition of raw cow’s milk.
Direction
Cepeda Sáez, Alberto (Tutorships)
LAMAS FREIRE, ALEXANDRE (Co-tutorships)
Cepeda Sáez, Alberto (Tutorships)
LAMAS FREIRE, ALEXANDRE (Co-tutorships)
Court
Leis Trabazo, María Rosaura (Coordinator)
Leis Trabazo, María Rosaura (Chairman)
MARTINON TORRES, FEDERICO (Secretary)
Concheiro Guisán, Ana (Member)
Leis Trabazo, María Rosaura (Coordinator)
Leis Trabazo, María Rosaura (Chairman)
MARTINON TORRES, FEDERICO (Secretary)
Concheiro Guisán, Ana (Member)
New metabolic pathways regulated by neddylation: possible implication in glycogen synthesis
Authorship
A.D.C.
Master in Biomedical Research
A.D.C.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Hepatic glycogen metabolism plays an essential role in mainteining glucose homeostasis. This is because glycogen serves as an important glucose reservoir or source depending on the nutritional status. Particularly, the key enzymes for the control of glycogen deposition are glycogen synthase, which elongates the chain, and glycogen phosphorylase, which shortens it. Additionally, the post-translational modification neddylation is the attachment of the small protein NEDD8 to target proteins through a three-step enzymatic cascade. Primarily, neddylation research has focused on its pathological role. However, little is known about its physiological function, especially that concerning glucose metabolism. Interestingly, a previous study suggests that liver glycogen synthase is a target protein for NEDD8. Furthermore, during nutrient deprivation conditions its presence bound to NEDD8 increases. Hence, the purpose of this Master’s dissertation is to study how nutritional status and neddylation influence liver glycogen synthase levels in vivo. To achieve this, different animal models of nutrient deprivation were used: 60% caloric restriction and different durations of fasting with or without refeeding. In addition, to inhibit neddylation the compound MLN4924 was used. Afterwards, liver expression and liver protein levels were analyzed by qPCR and Western Blot, respectively. After results analysis, higher levels of liver glycogen synthase were observed in the mouse models for nutrient deprivation. Furthermore, neddylation inhibition attenuated the increase of the enzyme’s levels in mice which followed caloric restriction. Taken together, the results of this study suggest that liver glycogen synthase levels are regulated by both nutritional state and by neddylation in vivo.
Hepatic glycogen metabolism plays an essential role in mainteining glucose homeostasis. This is because glycogen serves as an important glucose reservoir or source depending on the nutritional status. Particularly, the key enzymes for the control of glycogen deposition are glycogen synthase, which elongates the chain, and glycogen phosphorylase, which shortens it. Additionally, the post-translational modification neddylation is the attachment of the small protein NEDD8 to target proteins through a three-step enzymatic cascade. Primarily, neddylation research has focused on its pathological role. However, little is known about its physiological function, especially that concerning glucose metabolism. Interestingly, a previous study suggests that liver glycogen synthase is a target protein for NEDD8. Furthermore, during nutrient deprivation conditions its presence bound to NEDD8 increases. Hence, the purpose of this Master’s dissertation is to study how nutritional status and neddylation influence liver glycogen synthase levels in vivo. To achieve this, different animal models of nutrient deprivation were used: 60% caloric restriction and different durations of fasting with or without refeeding. In addition, to inhibit neddylation the compound MLN4924 was used. Afterwards, liver expression and liver protein levels were analyzed by qPCR and Western Blot, respectively. After results analysis, higher levels of liver glycogen synthase were observed in the mouse models for nutrient deprivation. Furthermore, neddylation inhibition attenuated the increase of the enzyme’s levels in mice which followed caloric restriction. Taken together, the results of this study suggest that liver glycogen synthase levels are regulated by both nutritional state and by neddylation in vivo.
Direction
NOGUEIRAS POZO, RUBEN (Tutorships)
Parracho Martínez, Tamara (Co-tutorships)
NOGUEIRAS POZO, RUBEN (Tutorships)
Parracho Martínez, Tamara (Co-tutorships)
Court
VIDAL FIGUEROA, ANXO (Chairman)
TOVAR CARRO, SULAY AMPARO (Secretary)
MARTIN CORA, FRANCISCO JAVIER (Member)
VIDAL FIGUEROA, ANXO (Chairman)
TOVAR CARRO, SULAY AMPARO (Secretary)
MARTIN CORA, FRANCISCO JAVIER (Member)
Evaluation of the performance of preliminary tests for fluid identification in routine forensic testing
Authorship
R.D.D.
Master in Biomedical Research
R.D.D.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Preliminary tests are presumptive tests widely used in forensic routine for the identification of biological fluids. However, despite having good sensitivity, their specificity is not as high as it should be, and false positives and negatives can be observed. Therefore, the main objective of the present work is to evaluate these aspects of the RSIDTM preliminary tests, designed for the detection of blood, semen or saliva. First, the detection limit of each of the tests was determined. Subsequently, their specificity was analyzed with different sample types and in the presence of non-target fluids, as well as under different experimental conditions. In addition, the effect of sample incubation time and sample age on the sensitivity and specificity of the kits was studied. Finally, the effect of subjectivity on the reading of the results was evaluated using RSIDTM Reader, a device designed to read the cassettes and record the results in an automated way. The results obtained help to optimize the use of these kits, both in relation to the technical aspects in the laboratory and in the interpretation of the results in forensic cases.
Preliminary tests are presumptive tests widely used in forensic routine for the identification of biological fluids. However, despite having good sensitivity, their specificity is not as high as it should be, and false positives and negatives can be observed. Therefore, the main objective of the present work is to evaluate these aspects of the RSIDTM preliminary tests, designed for the detection of blood, semen or saliva. First, the detection limit of each of the tests was determined. Subsequently, their specificity was analyzed with different sample types and in the presence of non-target fluids, as well as under different experimental conditions. In addition, the effect of sample incubation time and sample age on the sensitivity and specificity of the kits was studied. Finally, the effect of subjectivity on the reading of the results was evaluated using RSIDTM Reader, a device designed to read the cassettes and record the results in an automated way. The results obtained help to optimize the use of these kits, both in relation to the technical aspects in the laboratory and in the interpretation of the results in forensic cases.
Direction
LAREU HUIDOBRO, MARIA VICTORIA (Tutorships)
MOSQUERA MIGUEL, ANA (Co-tutorships)
LAREU HUIDOBRO, MARIA VICTORIA (Tutorships)
MOSQUERA MIGUEL, ANA (Co-tutorships)
Court
VIDAL FIGUEROA, ANXO (Chairman)
TOVAR CARRO, SULAY AMPARO (Secretary)
MARTIN CORA, FRANCISCO JAVIER (Member)
VIDAL FIGUEROA, ANXO (Chairman)
TOVAR CARRO, SULAY AMPARO (Secretary)
MARTIN CORA, FRANCISCO JAVIER (Member)
CCR9 as therapeutic target in lung cancer
Authorship
L.F.V.
Master in Biomedical Research
L.F.V.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Lung cancer is the type of cancer that causes the most deaths worldwide. It’s high mortality may be due to the diagnosis in late stages and to the development of chemoresistance and subsequent relapse. CCR9 is a chemokine receptor that is involved in cell behaviours associated with a higher aggressiveness, such as chemoresistance, invasion and metastasis, in different cancer types, including lung cancer. Due to its role in this pathology, in this work, the potential of CCR9 as a therapeutic target has been studied. For it, some phenotypic features associated with a higher aggressiveness, such as migration, chemoresistnce and proliferation, were compared between two lung adenocarcinoma cell lines, A549 WT, the parental one, and A549 CCR9 KO, in which this receptor was genetically inactivated. In this work, it has been observed that CCR9 knockout cells migrate significantly less and are significantly more sensitive to cisplatin than the WT cells. The conclusion of this work is that CCR9 has potential as a therapeutic target in lung cancer given that it promotes cell migration and chemoresistance in the context of this pathology.
Lung cancer is the type of cancer that causes the most deaths worldwide. It’s high mortality may be due to the diagnosis in late stages and to the development of chemoresistance and subsequent relapse. CCR9 is a chemokine receptor that is involved in cell behaviours associated with a higher aggressiveness, such as chemoresistance, invasion and metastasis, in different cancer types, including lung cancer. Due to its role in this pathology, in this work, the potential of CCR9 as a therapeutic target has been studied. For it, some phenotypic features associated with a higher aggressiveness, such as migration, chemoresistnce and proliferation, were compared between two lung adenocarcinoma cell lines, A549 WT, the parental one, and A549 CCR9 KO, in which this receptor was genetically inactivated. In this work, it has been observed that CCR9 knockout cells migrate significantly less and are significantly more sensitive to cisplatin than the WT cells. The conclusion of this work is that CCR9 has potential as a therapeutic target in lung cancer given that it promotes cell migration and chemoresistance in the context of this pathology.
Direction
VIDAL FIGUEROA, ANXO (Tutorships)
CARNEIRO FREIRE, CARMEN (Co-tutorships)
VIDAL FIGUEROA, ANXO (Tutorships)
CARNEIRO FREIRE, CARMEN (Co-tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
Search of ferroptosis biomarkers in metabolic diseases
Authorship
L.G.A.
Master in Biomedical Research
L.G.A.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Ferroptosis is a form of iron-dependent, regulated cell death characterized by the accumulation of lipid peroxides. It's implicated in multiple biological contexts such as aging, immunity, and cancer. However, although ferroptosis has been widely studied in other biological and pathological contexts, its specific role in metabolism and its functionality in adipose tissue remain unclear. In this context, there is a need to study the relationship between the different mechanisms involved in ferroptosis and obesity. This work focused on the analysis of gene expression variations of glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase family member 4 (ACSL4), dipeptidyl peptidase 4 (DPP4), ferroptosis suppressor protein 1 (FSP1), solute carrier family 7 member 11 (SLC7A11), and nuclear receptor coactivator 4 (NCOA4) in abdominal subcutaneous adipose tissue (SAT) of obese patients compared to control patients and patients after bariatric surgery (BS)-induced body weight normalization. The results indicate a possible greater vulnerability of SAT to oxidative stress and ferroptosis. Further studies are needed to determine whether the observed effects reflect a crucial role of ferroptosis in adipose tissue dysfunction in obesity and whether its modulation could represent a therapeutic strategy after CB-induced weight loss.
Ferroptosis is a form of iron-dependent, regulated cell death characterized by the accumulation of lipid peroxides. It's implicated in multiple biological contexts such as aging, immunity, and cancer. However, although ferroptosis has been widely studied in other biological and pathological contexts, its specific role in metabolism and its functionality in adipose tissue remain unclear. In this context, there is a need to study the relationship between the different mechanisms involved in ferroptosis and obesity. This work focused on the analysis of gene expression variations of glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase family member 4 (ACSL4), dipeptidyl peptidase 4 (DPP4), ferroptosis suppressor protein 1 (FSP1), solute carrier family 7 member 11 (SLC7A11), and nuclear receptor coactivator 4 (NCOA4) in abdominal subcutaneous adipose tissue (SAT) of obese patients compared to control patients and patients after bariatric surgery (BS)-induced body weight normalization. The results indicate a possible greater vulnerability of SAT to oxidative stress and ferroptosis. Further studies are needed to determine whether the observed effects reflect a crucial role of ferroptosis in adipose tissue dysfunction in obesity and whether its modulation could represent a therapeutic strategy after CB-induced weight loss.
Direction
TOVAR CARRO, SULAY AMPARO (Tutorships)
Fafián Labora, Juan Antonio (Co-tutorships)
Sangiao Albarellos, Susana (Co-tutorships)
TOVAR CARRO, SULAY AMPARO (Tutorships)
Fafián Labora, Juan Antonio (Co-tutorships)
Sangiao Albarellos, Susana (Co-tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
Metabolic role of insuline signaling in astrocytes.
Authorship
R.G.V.
Master in Biomedical Research
R.G.V.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
The Central Nervous System plays a fundamental role in the integration and coordination of metabolic and endocrine signals. The hypothalamus is the main region responsible for controlling metabolic homeostasis and generates responses to peripheral signals such as hormones, including insulin. This hormone is involved in glucose metabolism. It exerts its function through binding to its receptor, but it also acts by binding to the Insulin-like Growth Factor 1 (IGF-1) receptor (a receptor with a structure very similar to the insulin receptor) and to hybrid receptors composed of both types, thereby allowing activation of the same signaling pathways. In the Central Nervous System, insulin regulates glucose entrance into the brain. Moreover, its elimination in both the Central Nervous System and specifically in the hypothalamus causes alterations in glucose and lipid metabolism. This signaling in the brain is essential for the regulation of hepatic glucose and lipid metabolism. In addition to neurons, glial cells also possess this type of receptor. This study investigates both the individual role of the insulin receptor and its synergistic function with the Insulin-like Growth Factor 1 receptor in hypothalamic astrocytes, as well as the potential metabolic alterations in the liver. This process was carried out using two animal models. In one, insulin receptor ablation was induced, and in the other, a double ablation of the insulin receptor and the Insulin-like Growth Factor 1 receptor, both in the hypothalamic astrocytes of male mice. Through molecular and histological techniques, the results show that the combined action of both receptors in hypothalamic astrocytes is necessary to maintain hepatic glucose and lipid metabolism.
The Central Nervous System plays a fundamental role in the integration and coordination of metabolic and endocrine signals. The hypothalamus is the main region responsible for controlling metabolic homeostasis and generates responses to peripheral signals such as hormones, including insulin. This hormone is involved in glucose metabolism. It exerts its function through binding to its receptor, but it also acts by binding to the Insulin-like Growth Factor 1 (IGF-1) receptor (a receptor with a structure very similar to the insulin receptor) and to hybrid receptors composed of both types, thereby allowing activation of the same signaling pathways. In the Central Nervous System, insulin regulates glucose entrance into the brain. Moreover, its elimination in both the Central Nervous System and specifically in the hypothalamus causes alterations in glucose and lipid metabolism. This signaling in the brain is essential for the regulation of hepatic glucose and lipid metabolism. In addition to neurons, glial cells also possess this type of receptor. This study investigates both the individual role of the insulin receptor and its synergistic function with the Insulin-like Growth Factor 1 receptor in hypothalamic astrocytes, as well as the potential metabolic alterations in the liver. This process was carried out using two animal models. In one, insulin receptor ablation was induced, and in the other, a double ablation of the insulin receptor and the Insulin-like Growth Factor 1 receptor, both in the hypothalamic astrocytes of male mice. Through molecular and histological techniques, the results show that the combined action of both receptors in hypothalamic astrocytes is necessary to maintain hepatic glucose and lipid metabolism.
Direction
GONZALEZ GARCIA, ISMAEL (Tutorships)
GONZALEZ GARCIA, ISMAEL (Tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
Tanycytes and Aging: Validation of an In Vitro Model and Study of Potentially Involved Genes
Authorship
J.L.P.
Master in Biomedical Research
J.L.P.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
In recent years, a large part of scientific effort has focused on understanding the mechanisms of aging. To this end, this study focuses on tanycytes, some of the most affected cells by the aging process in the central nervous system, acting as a gateway for multiple metabolites into the hypothalamus. This work will validate the use of primary cultures for the in vitro study of the aging process in tanycytes and, if validated, the possible effects of the target Desmoglein 2 on this process will be studied. The results of this study validate the in vitro model for the study of aging and position Dsg2 as a promising target due to its effects on cell proliferation.
In recent years, a large part of scientific effort has focused on understanding the mechanisms of aging. To this end, this study focuses on tanycytes, some of the most affected cells by the aging process in the central nervous system, acting as a gateway for multiple metabolites into the hypothalamus. This work will validate the use of primary cultures for the in vitro study of the aging process in tanycytes and, if validated, the possible effects of the target Desmoglein 2 on this process will be studied. The results of this study validate the in vitro model for the study of aging and position Dsg2 as a promising target due to its effects on cell proliferation.
Direction
NOGUEIRAS POZO, RUBEN (Tutorships)
NOGUEIRAS POZO, RUBEN (Tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
Role of the PCK1 protein in the development of liver fibrosis
Authorship
B.L.P.
Master in Biomedical Research
B.L.P.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Phosphoenolpyruvate carboxykinase (PCK1) is a gluconeogenic enzyme involved in the energy homeostasis of hepatic glucose. Its deficiency in hepatocytes is known to be associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD); however, its role in hepatic stellate cells (HSCs), the main fibrogenic cells in the liver, remains unknown. HSCs are not traditionally considered gluconeogenic cells. However, during their activation, they undergo metabolic reprogramming characterized by a marked increase in glycolysis to meet the high energy and biosynthetic demands required for the acquisition of a profibrogenic phenotype. Based on this, the present study aimed to investigate whether PCK1, by regulating glucose metabolism in HSCs, could play a relevant role in this process and, therefore, in the development of hepatic fibrosis. To this end, the gene expression of PCK1 was analyzed both in in vitro human models of activated HSCs and in primary HSCs from mice with liver fibrosis, confirming a reduction in its expression levels. The decrease in PCK1 was also studied as a potential causal mechanism in fibrosis development. It was observed that both in in vitro human HSC models and in in vivo conditional knockdown models, fibrosis levels worsened and glycolytic capacity increased. Taken together, these results suggest a possible role for PCK1 downregulation in the development of fibrosis in the context of MASLD, by enhancing the glycolytic capacity of activated HSCs and thereby promoting their fibrogenic metabolism.
Phosphoenolpyruvate carboxykinase (PCK1) is a gluconeogenic enzyme involved in the energy homeostasis of hepatic glucose. Its deficiency in hepatocytes is known to be associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD); however, its role in hepatic stellate cells (HSCs), the main fibrogenic cells in the liver, remains unknown. HSCs are not traditionally considered gluconeogenic cells. However, during their activation, they undergo metabolic reprogramming characterized by a marked increase in glycolysis to meet the high energy and biosynthetic demands required for the acquisition of a profibrogenic phenotype. Based on this, the present study aimed to investigate whether PCK1, by regulating glucose metabolism in HSCs, could play a relevant role in this process and, therefore, in the development of hepatic fibrosis. To this end, the gene expression of PCK1 was analyzed both in in vitro human models of activated HSCs and in primary HSCs from mice with liver fibrosis, confirming a reduction in its expression levels. The decrease in PCK1 was also studied as a potential causal mechanism in fibrosis development. It was observed that both in in vitro human HSC models and in in vivo conditional knockdown models, fibrosis levels worsened and glycolytic capacity increased. Taken together, these results suggest a possible role for PCK1 downregulation in the development of fibrosis in the context of MASLD, by enhancing the glycolytic capacity of activated HSCs and thereby promoting their fibrogenic metabolism.
Direction
NOGUEIRAS POZO, RUBEN (Tutorships)
Nóvoa Deaño, Eva María (Co-tutorships)
NOGUEIRAS POZO, RUBEN (Tutorships)
Nóvoa Deaño, Eva María (Co-tutorships)
Court
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
DOMINGUEZ PUENTE, FERNANDO (Chairman)
CASTRO TUBIO, JOSE MANUEL (Secretary)
CASTRO PEREZ, MARIA DE LOS ANGELES (Member)
Biological Effects of AG5 on Cancer Cells at the Endoplasmic Reticulum Level
Authorship
O.L.V.
Master in Biomedical Research
O.L.V.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Cancer is a complex disease and one of the leading causes of death worldwide, characterised by metabolic alterations and therapeutic resistance. In this paper, the therapeutic potential of five-atom quantum atomic clusters (AQCs-Ag5) has been evaluated in two cell lines, focusing on their effect on endoplasmic reticulum stress and calcium signalling. AQCs-Ag5 treatment induces the accumulation of misfolded proteins in the endoplasmic reticulum, promoting the dissociation of BiP from the PERK sensor and its subsequent phosphorylation, which triggers eIF2 alpha phosphorylation, reduces global translation, and promotes the expression of ATF4 and CHOP - factors associated with apoptosis. The results suggest that these clusters induce calcium-related alterations affecting the morphology of both the endoplasmic reticulum and mitochondria, in addition to activating the unfolded protein response (UPR) pathway, with differences observed among the studied cell lines. These findings highlight the specificity of clusters as a promising therapeutic strategy against cancer.
Cancer is a complex disease and one of the leading causes of death worldwide, characterised by metabolic alterations and therapeutic resistance. In this paper, the therapeutic potential of five-atom quantum atomic clusters (AQCs-Ag5) has been evaluated in two cell lines, focusing on their effect on endoplasmic reticulum stress and calcium signalling. AQCs-Ag5 treatment induces the accumulation of misfolded proteins in the endoplasmic reticulum, promoting the dissociation of BiP from the PERK sensor and its subsequent phosphorylation, which triggers eIF2 alpha phosphorylation, reduces global translation, and promotes the expression of ATF4 and CHOP - factors associated with apoptosis. The results suggest that these clusters induce calcium-related alterations affecting the morphology of both the endoplasmic reticulum and mitochondria, in addition to activating the unfolded protein response (UPR) pathway, with differences observed among the studied cell lines. These findings highlight the specificity of clusters as a promising therapeutic strategy against cancer.
Direction
DOMINGUEZ PUENTE, FERNANDO (Tutorships)
PORTO GONZALEZ, VANESA (Co-tutorships)
DOMINGUEZ PUENTE, FERNANDO (Tutorships)
PORTO GONZALEZ, VANESA (Co-tutorships)
Court
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
Study of the functionality of the rare natural variant A55T of fractalkine receptor CX3CR1 in cell lines
Authorship
L.M.T.
Master in Biomedical Research
L.M.T.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Recent research in the field of Central Nervous System disease pharmacology links the fractalkine receptor CX3CR1, particularly its rare native variant CX3CR1-A55T, to neuropsychiatric disease phenotypes such as schizophrenia and autism. Interaction studies with beta-arrestins showed a decreased ability of the mutant receptor to promote translocation of these proteins to the plasma membrane compared to the native variant in response to fractalkine ligand. It has been suggested that the A55T variant is deficient in G protein interaction, but the kinetics of G protein dissociation in response to fractalkine have not been properly studied. The aim of this work was to evaluate the functionality of the rare A55T variant of the fractalkine receptor CX3CR1 in stable cell lines. The determination of the G protein activation kinetics of CX3CR1 and the CX3CR1-A55T mutant was performed using the Transduction Pathways assay platform, employing the Bioluminescence Resonance Energy Transfer technique, contemplating a previous step of optimization of the assay conditions in relation to the CX3CR1 native receptor. Complementary intracellular calcium assays in response to fractalkine were performed for both receptor types. The efficiency of G protein interaction with the receptor in response to fractalkine, as well as the potency with which fractalkine promotes such interaction, were not affected in the CX3CR1-A55T variant with respect to the native CX3CR1 receptor. Intracellular calcium signaling assays showed transient increases of this ion in a concentration-dependent manner in response to increasing concentrations of fractalkine, both for the native receptor and for its mutated variant. The results obtained suggest that the G protein-dependent signaling pathway is functional for the CX3CR1-A55T mutant.
Recent research in the field of Central Nervous System disease pharmacology links the fractalkine receptor CX3CR1, particularly its rare native variant CX3CR1-A55T, to neuropsychiatric disease phenotypes such as schizophrenia and autism. Interaction studies with beta-arrestins showed a decreased ability of the mutant receptor to promote translocation of these proteins to the plasma membrane compared to the native variant in response to fractalkine ligand. It has been suggested that the A55T variant is deficient in G protein interaction, but the kinetics of G protein dissociation in response to fractalkine have not been properly studied. The aim of this work was to evaluate the functionality of the rare A55T variant of the fractalkine receptor CX3CR1 in stable cell lines. The determination of the G protein activation kinetics of CX3CR1 and the CX3CR1-A55T mutant was performed using the Transduction Pathways assay platform, employing the Bioluminescence Resonance Energy Transfer technique, contemplating a previous step of optimization of the assay conditions in relation to the CX3CR1 native receptor. Complementary intracellular calcium assays in response to fractalkine were performed for both receptor types. The efficiency of G protein interaction with the receptor in response to fractalkine, as well as the potency with which fractalkine promotes such interaction, were not affected in the CX3CR1-A55T variant with respect to the native CX3CR1 receptor. Intracellular calcium signaling assays showed transient increases of this ion in a concentration-dependent manner in response to increasing concentrations of fractalkine, both for the native receptor and for its mutated variant. The results obtained suggest that the G protein-dependent signaling pathway is functional for the CX3CR1-A55T mutant.
Direction
CASTRO PEREZ, MARIA DE LOS ANGELES (Tutorships)
CASTRO PEREZ, MARIA DE LOS ANGELES (Tutorships)
Court
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
Systematic review on the relationship between zinc supplementation and metabolic hormone levels: ghrelin, leptin, thyroid hormone, insulin, adiponectin, and body composition in pediatric patients with overweight and obesity
Authorship
D.D.M.C.
Master in Genetic, Nutritional and Environmental Determinants concerning Growth and Development-NUTRENVIGEN G+D Factors
D.D.M.C.
Master in Genetic, Nutritional and Environmental Determinants concerning Growth and Development-NUTRENVIGEN G+D Factors
Defense date
07.17.2025 09:00
07.17.2025 09:00
Summary
Introduction: Childhood obesity is a growing public health concern, associated with hormonal disturbances that affect metabolism and body composition. Zinc supplementation has been proposed as a potential modulator of these alterations due to its involvement in several metabolic pathways. This systematic review aims to evaluate the available evidence on the effect of oral zinc on metabolic hormones and anthropometric parameters in overweight or obese children and adolescents. Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science 2005 - 2025, following PRISMA guidelines. Randomized controlled trials and quasiexperimental studies were included if they assessed the effect of zinc on at least one metabolic hormone: insulin, leptin, ghrelin, adiponectin, thyroid hormones and one body composition variable: BMI, fat mass, waist circumference in pediatric populations with excess weight. Study quality and risk of bias were assessed using the RoB 2.0 tools. Results: Out of 183 studies identified, 4 met the inclusion criteria. Three were randomized controlled trials and one was quasi-experimental. The total sample comprised 280 participants aged 6-15 years, including both boys and girls in prepubertal stages. Most studies reported significant improvements in insulin and leptin levels, as well as reductions in BMI and waist circumference after zinc supplementation. Conclusion: Evidence suggests that zinc may have beneficial effects on the hormonal profile and body composition of overweight or obese children. However, the limited number of studies and methodological heterogeneity restrict generalization. Further well-designed trials with long-term follow-up are needed to confirm these effects and guide clinical recommendations.
Introduction: Childhood obesity is a growing public health concern, associated with hormonal disturbances that affect metabolism and body composition. Zinc supplementation has been proposed as a potential modulator of these alterations due to its involvement in several metabolic pathways. This systematic review aims to evaluate the available evidence on the effect of oral zinc on metabolic hormones and anthropometric parameters in overweight or obese children and adolescents. Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science 2005 - 2025, following PRISMA guidelines. Randomized controlled trials and quasiexperimental studies were included if they assessed the effect of zinc on at least one metabolic hormone: insulin, leptin, ghrelin, adiponectin, thyroid hormones and one body composition variable: BMI, fat mass, waist circumference in pediatric populations with excess weight. Study quality and risk of bias were assessed using the RoB 2.0 tools. Results: Out of 183 studies identified, 4 met the inclusion criteria. Three were randomized controlled trials and one was quasi-experimental. The total sample comprised 280 participants aged 6-15 years, including both boys and girls in prepubertal stages. Most studies reported significant improvements in insulin and leptin levels, as well as reductions in BMI and waist circumference after zinc supplementation. Conclusion: Evidence suggests that zinc may have beneficial effects on the hormonal profile and body composition of overweight or obese children. However, the limited number of studies and methodological heterogeneity restrict generalization. Further well-designed trials with long-term follow-up are needed to confirm these effects and guide clinical recommendations.
Direction
Leis Trabazo, María Rosaura (Tutorships)
Leis Trabazo, María Rosaura (Tutorships)
Court
Leis Trabazo, María Rosaura (Coordinator)
COUCE PICO, MARIA DE LA LUZ (Chairman)
MARTINON TORRES, FEDERICO (Secretary)
Concheiro Guisán, Ana (Member)
Leis Trabazo, María Rosaura (Coordinator)
COUCE PICO, MARIA DE LA LUZ (Chairman)
MARTINON TORRES, FEDERICO (Secretary)
Concheiro Guisán, Ana (Member)
Study of the effect of the tumor microenvironment on red blood cells in the context of breast cancer
Authorship
M.M.V.
Master in Biomedical Research
M.M.V.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
This work explores the impact of the tumor microenvironment on red blood cells and how this can influence breast cancer progression, especially in its metastatic form. Red blood cells have been shown to play an active role in adhering to tumor cells and modulating their behavior, despite being little studied in the tumor context. Using in vitro experimental models that simulate inflammatory conditions of the tumor microenvironment (such as exposure to IL-6, hypoxia, or media conditioned by tumor cells), the ability of red blood cells to adhere to MDA-MB-231 tumor cells was evaluated. Additionally, changes in the expression of genes related to tumor progression (VIM and PAK4) were analyzed in the tumor cells, as well as the expression of the CD275/ICOSL protein after contact with red blood cells. The results show that red blood cells from patients with metastatic breast cancer exhibit a greater adhesion capacity, and “simulated patient” models were developed that partially replicate this effect in the laboratory. This validates their experimental utility and reduces the interindividual variability of biological samples. Furthermore, it is also demonstrated that red blood cells are capable of inducing molecular changes in tumor cells, including an increase in CD275 expression. This study suggests that red blood cells could act as active components and/or mediators of the tumor microenvironment, participating in mechanisms of metastatic dissemination, immune modulation, and tumor progression. These findings open new lines of research aimed at characterizing the factors involved, especially the tumor secretome and extracellular vesicles, and propose the development of more complex co-culture models that integrate immune cells
This work explores the impact of the tumor microenvironment on red blood cells and how this can influence breast cancer progression, especially in its metastatic form. Red blood cells have been shown to play an active role in adhering to tumor cells and modulating their behavior, despite being little studied in the tumor context. Using in vitro experimental models that simulate inflammatory conditions of the tumor microenvironment (such as exposure to IL-6, hypoxia, or media conditioned by tumor cells), the ability of red blood cells to adhere to MDA-MB-231 tumor cells was evaluated. Additionally, changes in the expression of genes related to tumor progression (VIM and PAK4) were analyzed in the tumor cells, as well as the expression of the CD275/ICOSL protein after contact with red blood cells. The results show that red blood cells from patients with metastatic breast cancer exhibit a greater adhesion capacity, and “simulated patient” models were developed that partially replicate this effect in the laboratory. This validates their experimental utility and reduces the interindividual variability of biological samples. Furthermore, it is also demonstrated that red blood cells are capable of inducing molecular changes in tumor cells, including an increase in CD275 expression. This study suggests that red blood cells could act as active components and/or mediators of the tumor microenvironment, participating in mechanisms of metastatic dissemination, immune modulation, and tumor progression. These findings open new lines of research aimed at characterizing the factors involved, especially the tumor secretome and extracellular vesicles, and propose the development of more complex co-culture models that integrate immune cells
Direction
LOPEZ LOPEZ, RAFAEL (Tutorships)
Costa Nogueira, Clotilde (Co-tutorships)
LOPEZ LOPEZ, RAFAEL (Tutorships)
Costa Nogueira, Clotilde (Co-tutorships)
Court
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
Role of SPARC in exosome-mediated communication of Circulating Tumor Cells (CTCs) in breast cancer
Authorship
E.P.H.
Master in Biomedical Research
E.P.H.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Circulating tumor cells (CTCs) and CTC clusters (cCTCs) are considered key elements in the development of metastasis in breast cancer. Recently, their metastatic potential has been associated with an overexpression of the SPARC protein. This work addresses the possible secretion of SPARC by these cells through exosomes and the implication that this mechanism could have in tumor dissemination and progression. To this end, both the mCTC cell line, a cellular model derived from a mouse xenograft resembling cCTCs, and its parental line MDA-MB-231 were used. As part of an initial characterization, an intracellular SPARC staining was optimized for analysis by flow cytometry. Subsequently, an exosome extraction method based on ultracentrifugation was developed, followed by the evaluation of SPARC presence in the exosomes and the study of its role in cell migration through functional assays. Firstly, intracellular SPARC staining validated its overexpression in mCTCs compared to MDA-MB-231. On the other hand, exosome extraction through cell culture in the absence of FBS and serial ultracentrifugations of the medium constituted a good initial approach, although further validation is still required. Likewise, exosomal lysates from the mCTC line showed a higher amount of SPARC than those from MDA-MB-231, suggesting greater incorporation of the protein into the exosomes. However, it remains necessary to confirm that the analyzed amount of these vesicles is equivalent in both lines. Finally, SPARC’s action in cell migration appears to depend both on its concentration and on interaction with other factors present in the medium. Due to limitations in time, cells, and material resources, the described results do not reach statistical robustness. Nevertheless, they provide a solid basis to continue deepening this line of research, potentially laying the groundwork to clarify how exosomal conditioning influences the tumor nesting profile.
Circulating tumor cells (CTCs) and CTC clusters (cCTCs) are considered key elements in the development of metastasis in breast cancer. Recently, their metastatic potential has been associated with an overexpression of the SPARC protein. This work addresses the possible secretion of SPARC by these cells through exosomes and the implication that this mechanism could have in tumor dissemination and progression. To this end, both the mCTC cell line, a cellular model derived from a mouse xenograft resembling cCTCs, and its parental line MDA-MB-231 were used. As part of an initial characterization, an intracellular SPARC staining was optimized for analysis by flow cytometry. Subsequently, an exosome extraction method based on ultracentrifugation was developed, followed by the evaluation of SPARC presence in the exosomes and the study of its role in cell migration through functional assays. Firstly, intracellular SPARC staining validated its overexpression in mCTCs compared to MDA-MB-231. On the other hand, exosome extraction through cell culture in the absence of FBS and serial ultracentrifugations of the medium constituted a good initial approach, although further validation is still required. Likewise, exosomal lysates from the mCTC line showed a higher amount of SPARC than those from MDA-MB-231, suggesting greater incorporation of the protein into the exosomes. However, it remains necessary to confirm that the analyzed amount of these vesicles is equivalent in both lines. Finally, SPARC’s action in cell migration appears to depend both on its concentration and on interaction with other factors present in the medium. Due to limitations in time, cells, and material resources, the described results do not reach statistical robustness. Nevertheless, they provide a solid basis to continue deepening this line of research, potentially laying the groundwork to clarify how exosomal conditioning influences the tumor nesting profile.
Direction
LOPEZ LOPEZ, RAFAEL (Tutorships)
Piñeiro Cid, Roberto (Co-tutorships)
LOPEZ LOPEZ, RAFAEL (Tutorships)
Piñeiro Cid, Roberto (Co-tutorships)
Court
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
Study of genomic instability induced by LINE-1 retrotransposition.
Authorship
U.P.M.
Master in Biomedical Research
U.P.M.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
Nearly half of the human genome is composed of mobile elements, repetitive sequences with the potential to transpose to other locations within the genome. Among these, LINE-1 stands out: as an active retrotransposon, L1 contributes to genomic variation and has been implicated in a wide range of human diseases. Many aspects of this mobile element and its transposition cycle remain unknown, which could be adressed through studies in established cell lines. This work aims to carry out the initial steps of a protocol for inserting an exogenous L1 into both tumour and non-tumour cells. To this end, HeLa and RPE-1 cells were transfected with plasmid vectors encoding L1 elements, and both transfection efficiency and the activity of these elements were analyzed. Prior to this, the plasmids were amplified and evaluated. The protocol was successfully implemented in both cell lines and shows high applicability in HeLa cells, although the results suggest further optimization of the assay conditions for RPE-1 cells.
Nearly half of the human genome is composed of mobile elements, repetitive sequences with the potential to transpose to other locations within the genome. Among these, LINE-1 stands out: as an active retrotransposon, L1 contributes to genomic variation and has been implicated in a wide range of human diseases. Many aspects of this mobile element and its transposition cycle remain unknown, which could be adressed through studies in established cell lines. This work aims to carry out the initial steps of a protocol for inserting an exogenous L1 into both tumour and non-tumour cells. To this end, HeLa and RPE-1 cells were transfected with plasmid vectors encoding L1 elements, and both transfection efficiency and the activity of these elements were analyzed. Prior to this, the plasmids were amplified and evaluated. The protocol was successfully implemented in both cell lines and shows high applicability in HeLa cells, although the results suggest further optimization of the assay conditions for RPE-1 cells.
Direction
CASTRO TUBIO, JOSE MANUEL (Tutorships)
Oitabén Fernández, Ana (Co-tutorships)
Sánchez Luque, Francisco José (Co-tutorships)
CASTRO TUBIO, JOSE MANUEL (Tutorships)
Oitabén Fernández, Ana (Co-tutorships)
Sánchez Luque, Francisco José (Co-tutorships)
Court
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
Advanced in vitro models of cerebral ischemia/reperfusion
Authorship
D.R.S.
Master in Biomedical Research
D.R.S.
Master in Biomedical Research
Defense date
07.17.2025 09:30
07.17.2025 09:30
Summary
In this Master's Thesis, a perfusable vessel-on-a-chip model was developed to study ischemia/reperfusion injury in human umbilical vein endothelial cells, within a biomimetic context of ischemic stroke. First, it was established that an OGD (oxygen and glucose deprivation) period of 1 hour was sufficient to maintain an adequate cell density for comparative morphological and expression analyses under different conditions in a functional endothelial monolayer. The study continued by validating a 3-hour reperfusion period as appropriate to ensure partial recovery of the monolayer, as assessed by nuclear size and cytoplasmic area per cell. Additionally, the expression of Fn14 (fibroblast growth factor-inducible 14) was examined under different experimental conditions of perfusion, ischemia, and reperfusion. Fn14 expression increased in both ischemic and reperfusion conditions, reaching a threefold increase over basal levels after 3 hours of reperfusion, with statistically significant differences in both reperfusion conditions. In parallel, the cytotoxicity of recombinant TWEAK (tumor necrosis factor-like weak inducer of apoptosis) was assessed in 2D cultures of endothelial cells at 1, 3, 24, and 48 hours of incubation, showing that TWEAK disrupts the monolayer through mechanisms other than loss of cell viability. Finally, the release of two inflammatory mediators- soluble E-selectin and MCP-1 (monocyte chemoattractant protein-1)- was evaluated. While MCP-1 was detectable only under basal perfusion conditions, soluble E-selectin was not detected in any of the conditions tested. In conclusion, this vessel-on-a-chip model enabled the study of ischemia/reperfusion damage after 1 hour of OGD, revealing a marked upregulation of Fn14 and morphological recovery after 3 hours of reperfusion. Moreover, TWEAK was shown not to impair endothelial viability under static conditions. Lastly, the release of soluble mediators after reperfusion was undetectable, indicating that the method is not optimized for this type of analysis.
In this Master's Thesis, a perfusable vessel-on-a-chip model was developed to study ischemia/reperfusion injury in human umbilical vein endothelial cells, within a biomimetic context of ischemic stroke. First, it was established that an OGD (oxygen and glucose deprivation) period of 1 hour was sufficient to maintain an adequate cell density for comparative morphological and expression analyses under different conditions in a functional endothelial monolayer. The study continued by validating a 3-hour reperfusion period as appropriate to ensure partial recovery of the monolayer, as assessed by nuclear size and cytoplasmic area per cell. Additionally, the expression of Fn14 (fibroblast growth factor-inducible 14) was examined under different experimental conditions of perfusion, ischemia, and reperfusion. Fn14 expression increased in both ischemic and reperfusion conditions, reaching a threefold increase over basal levels after 3 hours of reperfusion, with statistically significant differences in both reperfusion conditions. In parallel, the cytotoxicity of recombinant TWEAK (tumor necrosis factor-like weak inducer of apoptosis) was assessed in 2D cultures of endothelial cells at 1, 3, 24, and 48 hours of incubation, showing that TWEAK disrupts the monolayer through mechanisms other than loss of cell viability. Finally, the release of two inflammatory mediators- soluble E-selectin and MCP-1 (monocyte chemoattractant protein-1)- was evaluated. While MCP-1 was detectable only under basal perfusion conditions, soluble E-selectin was not detected in any of the conditions tested. In conclusion, this vessel-on-a-chip model enabled the study of ischemia/reperfusion damage after 1 hour of OGD, revealing a marked upregulation of Fn14 and morphological recovery after 3 hours of reperfusion. Moreover, TWEAK was shown not to impair endothelial viability under static conditions. Lastly, the release of soluble mediators after reperfusion was undetectable, indicating that the method is not optimized for this type of analysis.
Direction
ALVAREZ CASTRO, EZEQUIEL (Tutorships)
IGLESIAS REY, RAMON (Co-tutorships)
ALVAREZ CASTRO, EZEQUIEL (Tutorships)
IGLESIAS REY, RAMON (Co-tutorships)
Court
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
SALAS ELLACURIAGA, ANTONIO (Chairman)
GOMEZ DURAN, AURORA (Secretary)
González Blanco, Miguel (Member)
The Impact of Early Nutrition on Child Neurodevelopment
Authorship
A.S.P.
Master in Genetic, Nutritional and Environmental Determinants concerning Growth and Development-NUTRENVIGEN G+D Factors
A.S.P.
Master in Genetic, Nutritional and Environmental Determinants concerning Growth and Development-NUTRENVIGEN G+D Factors
Defense date
07.17.2025 09:00
07.17.2025 09:00
Summary
Introduction: Child neurodevelopment is a complex process that is highly sensitive to environmental influences, with nutrition playing a key role. During the first years of life, particularly within the first 1,000 days, the brain undergoes rapid growth that requires optimal nutrient intake to ensure proper functional and structural maturation. Objective: To analyze the relationship between dietary patterns in early childhood and the risk of developing neurodevelopmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Methodology: A qualitative systematic review of scientific literature published between 2017 and 2025 was conducted. Databases such as PubMed, Scopus, Web of Science, and Google Scholar were consulted, selecting observational studies, systematic reviews, and clinical trials involving children aged 0 to 12 years. Results: Evidence suggests that healthy dietary patterns, such as the Mediterranean diet, are associated with improved cognitive, emotional, and behavioral outcomes, and a lower incidence of ADHD and ASD. In contrast, diets high in ultra-processed foods, added sugars, trans fats, and low in essential micronutrients are linked to impairments in attention, language, and behavior. Additionally, mechanisms such as intestinal dysbiosis, low-grade systemic inflammation, and epigenetic changes help explain this relationship. Conclusions: The quality of early childhood nutrition is a key determinant in neurological development. Promoting adequate nutrition from the earliest stages of life can be an effective strategy for preventing neurodevelopmental disorders.
Introduction: Child neurodevelopment is a complex process that is highly sensitive to environmental influences, with nutrition playing a key role. During the first years of life, particularly within the first 1,000 days, the brain undergoes rapid growth that requires optimal nutrient intake to ensure proper functional and structural maturation. Objective: To analyze the relationship between dietary patterns in early childhood and the risk of developing neurodevelopmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Methodology: A qualitative systematic review of scientific literature published between 2017 and 2025 was conducted. Databases such as PubMed, Scopus, Web of Science, and Google Scholar were consulted, selecting observational studies, systematic reviews, and clinical trials involving children aged 0 to 12 years. Results: Evidence suggests that healthy dietary patterns, such as the Mediterranean diet, are associated with improved cognitive, emotional, and behavioral outcomes, and a lower incidence of ADHD and ASD. In contrast, diets high in ultra-processed foods, added sugars, trans fats, and low in essential micronutrients are linked to impairments in attention, language, and behavior. Additionally, mechanisms such as intestinal dysbiosis, low-grade systemic inflammation, and epigenetic changes help explain this relationship. Conclusions: The quality of early childhood nutrition is a key determinant in neurological development. Promoting adequate nutrition from the earliest stages of life can be an effective strategy for preventing neurodevelopmental disorders.
Direction
Leis Trabazo, María Rosaura (Tutorships)
Martínez Llorente, Antonia (Co-tutorships)
Leis Trabazo, María Rosaura (Tutorships)
Martínez Llorente, Antonia (Co-tutorships)
Court
Leis Trabazo, María Rosaura (Coordinator)
COUCE PICO, MARIA DE LA LUZ (Chairman)
MARTINON TORRES, FEDERICO (Secretary)
Concheiro Guisán, Ana (Member)
Leis Trabazo, María Rosaura (Coordinator)
COUCE PICO, MARIA DE LA LUZ (Chairman)
MARTINON TORRES, FEDERICO (Secretary)
Concheiro Guisán, Ana (Member)
Systematic review on the effect of diet on fetal neurodevelopment
Authorship
A.S.P.
Master in Genetic, Nutritional and Environmental Determinants concerning Growth and Development-NUTRENVIGEN G+D Factors
A.S.P.
Master in Genetic, Nutritional and Environmental Determinants concerning Growth and Development-NUTRENVIGEN G+D Factors
Defense date
07.17.2025 09:00
07.17.2025 09:00
Summary
Introduction and objectives: Fetal neurodevelopment is essential for establishing the structural and functional foundations of the nervous system, with critical implications for postnatal cognitive, emotional, and motor development. Maternal nutrition plays a key role in these processes. This systematic review aims to synthesize current evidence on the impact of maternal diet during pregnancy on fetal neurodevelopment, identifying specific dietary patterns and nutrients involved. Methods: A systematic review was conducted following PRISMA guidelines, using PubMed, Google Scholar, and Embase databases. Studies published between 2005 and 2025 in English or Spanish were included. Eligible designs comprised observational studies, prospective cohorts, randomized clinical trials, systematic reviews, meta-analyses, and narrative reviews. Results: A total of 28 relevant studies were identified, analyzing over 25,000 motherchild dyads through various methodological designs, with follow-ups ranging from birth to adolescence. The findings show that healthy dietary patterns, such as the Mediterranean diet, are consistently associated with better neurocognitive outcomes in children. Nutrients such as omega3 fatty acids, choline, vitamin B12, and zinc were found to be particularly beneficial. In contrast, diets high in ultra-processed foods or with an imbalanced omega6/omega3 ratio were linked to poorer outcomes. Maternal stress and socioeconomic context emerged as key modulators of these effects. Conclusions: Maternal nutrition has a significant impact on fetal neurodevelopment. Promoting balanced diets, nutritional education, and supplementation strategies during pregnancy may improve long-term child neurological health.
Introduction and objectives: Fetal neurodevelopment is essential for establishing the structural and functional foundations of the nervous system, with critical implications for postnatal cognitive, emotional, and motor development. Maternal nutrition plays a key role in these processes. This systematic review aims to synthesize current evidence on the impact of maternal diet during pregnancy on fetal neurodevelopment, identifying specific dietary patterns and nutrients involved. Methods: A systematic review was conducted following PRISMA guidelines, using PubMed, Google Scholar, and Embase databases. Studies published between 2005 and 2025 in English or Spanish were included. Eligible designs comprised observational studies, prospective cohorts, randomized clinical trials, systematic reviews, meta-analyses, and narrative reviews. Results: A total of 28 relevant studies were identified, analyzing over 25,000 motherchild dyads through various methodological designs, with follow-ups ranging from birth to adolescence. The findings show that healthy dietary patterns, such as the Mediterranean diet, are consistently associated with better neurocognitive outcomes in children. Nutrients such as omega3 fatty acids, choline, vitamin B12, and zinc were found to be particularly beneficial. In contrast, diets high in ultra-processed foods or with an imbalanced omega6/omega3 ratio were linked to poorer outcomes. Maternal stress and socioeconomic context emerged as key modulators of these effects. Conclusions: Maternal nutrition has a significant impact on fetal neurodevelopment. Promoting balanced diets, nutritional education, and supplementation strategies during pregnancy may improve long-term child neurological health.
Direction
Leis Trabazo, María Rosaura (Tutorships)
Leis Trabazo, María Rosaura (Tutorships)
Court
Leis Trabazo, María Rosaura (Coordinator)
COUCE PICO, MARIA DE LA LUZ (Chairman)
MARTINON TORRES, FEDERICO (Secretary)
Concheiro Guisán, Ana (Member)
Leis Trabazo, María Rosaura (Coordinator)
COUCE PICO, MARIA DE LA LUZ (Chairman)
MARTINON TORRES, FEDERICO (Secretary)
Concheiro Guisán, Ana (Member)