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Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease characterized by severe muscle weakness mainly due to degeneration and death of motor neurons. A peculiarity of the neurodegenerative processes is the variable susceptibility among distinct neuronal populations, exemplified by the contrasting resilience of motor neurons innervating the ocular motor system and the more vulnerable facial and hypoglossal motor neurons. The crucial role of vascular endothelial growth factor (VEGF) as a neuroprotective factor in the nervous system is wellestablished since a deficit of VEGF has been related to motoneuronal degeneration. In this study, we investigated the survival of ocular, facial, and hypoglossal motor neurons utilizing the murine SOD1G93A ALS model at various stages of the disease. Our primary objective was to determine whether the survival of the different brainstem motor neurons was linked to disparate VEGF expression levels in resilient and susceptible motor neurons throughout neurodegeneration. Our findings revealed a selective loss of motor neurons exclusively within the vulnerable nuclei. Furthermore, a significantly higher level of VEGF was detected in the more resistant motor neurons, the extraocular ones. We also examined whether TDP-43 dynamics in the brainstem motor neuron of SOD mice was altered. Our data suggests that the increased VEGF levels observed in extraocular motor neurons may potentially underlie their resistance during the neurodegenerative processes in ALS in a TDP-43-independent manner. Our work might help to better understand the underlying mechanisms of selective vulnerability of motor neurons in ALS.

The incorporation of novel, functional, and sustainable foods in human diets is increasing because of their beneficial effects and environmental-friendly nature. Chia (Salvia hispanica L.) has proved to be a suitable source of bioactive peptides via enzymatic hydrolysis. These peptides could be responsible for modulating several physiological processes if able to reach the target organ. The bioavailable peptides contained in a hydrolysate obtained with Alcalase, as functional foods, were identified using a transwell system with Caco-2 cell culture as the absorption model. Furthermore, 20 unique peptides with a molecular weight lower than 1000 Da and the higher statistical significance of the peptide-precursor spectrum match (−10 log P) were assessed by in silico tools to suggest which peptides could be those exerting the demonstrated bioactivity. From the characterized peptides, considering the molecular features and the results obtained, the peptides AGDAHWTY, VDAHPIKAM, PNYHPNPR, and ALPPGAVHW are anticipated to be contributing to the antioxidant and/or ACE inhibitor activity of the chia protein hydrolysates.

Dendritic cells (DCs) serve as professional antigen-presenting cells (APC) bridging innate and adaptive immunity, playing an essential role in triggering specific cellular and humoral responses against tumor and infectious antigens. Consequently, various DC-based antitumor therapeutic strategies have been developed, particularly vaccines, and have been intensively investigated specifically in the context of acute myeloid leukemia (AML). This hematological malignancy mainly affects the elderly population (those aged over 65), which usually presents a high rate of therapeutic failure and an unfavorable prognosis. In this review, we examine the current state of development and progress of vaccines in AML. The findings evidence the possible administration of DC-based vaccines as an adjuvant treatment in AML following initial therapy. Furthermore, the therapy demonstrates promising outcomes in preventing or delaying tumor relapse and exhibits synergistic effects when combined with other treatments during relapses or disease progression. On the other hand, the remarkable success observed with RNA vaccines for COVID-19, delivered in lipid nanoparticles, has revealed the efficacy and effectiveness of these types of vectors, prompting further exploration and their potential application in AML, as well as other neoplasms, loading them with tumor RNA.

La enfermedad de Behçet (BD) es una vasculitis sistémica recurrente, inmunomediada y de origen multifactorial. El factor genético mejor conocido es un gen HLA de clase-I, HLAB51, siendo las causas de esta asociación aún desconocidas. Las moléculas HLA-I modulan la actividad de células T-CD8 y NK a través de su función como ligandos de KIR, y como reguladoras de la expresión y afinidad de HLA-E por receptores NKG2/CD94 a través de la presentación de nonapéptidos derivados de su péptido señal. Este sistema tiene una gran complejidad condicionada por el elevado grado de polimorfismo. El objetivo fue analizar la implicación de las células NK en BD a través del estudio de las moléculas HLA-I como ligandos de KIR y como moduladores de HLA-E; analizar la dotación de genes KIR; y examinar polimorfismos funcionales en KIR3DL1/S1, KIRDS4, y en HLA-E. Para ello, se realizó un estudio de casos y controles con estrategia de genes candidatos que incluyó 466 pacientes procedentes de 17 hospitales españoles, y 444 controles. En el análisis de los cuatro epítopos HLA-I ligandos de KIR, se encontró que sólo A3/11 estaba asociado como factor de protección independiente de HLA-B*51. El estudio de nonapéptidos que presenta HLA-E reveló que las moléculas HLA-A con VMAPRTLLL se comportarían como factores de protección y VMAPRTLVL como factores de riesgo. No se observaron diferencias en la distribución de genes KIR, aunque nuestros resultados sugieren asociación protectora del grupo de alelos 3DL1*004. Por último, nuestros resultados no sugieren relevancia del polimorfismo HLA-E. Así, nuestros resultados sugieren que la predisposición a BD por moléculas HLA-I puede estar relacionada con su función como moduladoras de NK, operando mecanismos con mayor peso de las interacciones HLA-KIR en individuos con moléculas HLA de riesgo, y de las interacciones HLAE-NKG2/CD94 en individuos sin moléculas de riesgo.

La esclerosis múltiple (EM) es una enfermedad inflamatoria, desmielinizante y neurodegenerativa del sistema nervioso central. El curso clínico de la enfermedad se clasifica en varios subtipos. El 85% de los pacientes presentan un curso clínico conocido como forma remitente-recurrente o remitente-recidivante, caracterizado por la aparición de episodios o brotes de disfunción neurológica más o menos reversibles, que se repiten cada cierto tiempo. Tras un periodo variable de tiempo de unos 10 años, casi un 50% de los pacientes pasan del curso en brotes a un curso progresivo, denominado forma secundaria progresiva. Por otra parte, alrededor de un 15% de los pacientes desarrollan un fenotipo que se caracteriza por una progresión constante desde el inicio de la enfermedad, conocida como forma progresiva primaria. El diagnóstico clínico se realiza considerando criterios de diseminación espacial y de dispersión temporal, valorados mediante resonancia magnética nuclear (criterios de McDonald 2017), además de otras pruebas complementarias, como el estudio del líquido cefalorraquídeo. Sin embargo, las diferentes pruebas diagnósticas presentan limitaciones para predecir de forma precisa el curso clínico de la enfermedad. El diagnóstico temprano de las formas progresivas de la enfermedad es un tema de gran interés, ya que permitiría acortar los tiempos de tratamiento. Para ello, es indispensable disponer de biomarcadores que sean altamente específicos y sensibles. El objetivo principal de la presente tesis ha sido evaluar la utilidad del índice kappa como indicador biológico de las formas progresivas de EM, y su relación con otras variables, con el fin de establecer un algoritmo pronóstico de progresión. Según nuestros resultados, los valores del índice de IgG e índice kappa presentaron niveles moderados en los fenotipos progresivos con respecto al fenotipo remitente-recurrente. El punto de corte calculado para la estratificación entre subtipos progresivos y subtipos remitentes

Melatonin is the major product both synthesized and secreted by the pineal gland during the night period and it is the principal chronobiotic hormone that regulates the circadian rhythms and seasonal changes in vertebrate biology. Moreover, melatonin shows both a broad distribution along the phylogenetically distant organisms and a high functional versatility. At the present time, a significant amount of experimental evidence has been reported in scientific literature and has clearly shown a functional relationship between the endocrine, nervous, and immune systems. The biochemistry basis of the functional communication between these systems is the utilization of a common chemicals signals. In this framework, at present melatonin is considered to be a relevant member of the so-called neuro-endocrine-immunological network. Thus, both in vivo and in vitro investigations conducted in both experimental animals and humans, have clearly documented that melatonin has an important immunomodulatory role. However, most of the published results refer to information on T lymphocytes, i.e., cellmediated immunity. On the contrary, fewer studies have been carried out on B lymphocytes, the cells responsible for the so-called humoral immunity. In this review, we have focused on the biological role of melatonin in the humoral immunity. More precisely, we report the actions of melatonin on B lymphocytes biology and on the production of different types of antibodies.

Over the past 15 years, the field of immunometabolism has seen significant advancements, delving into the complex interactions between the immune system and metabolic processes to modulate immune function. This rapidly expanding field has depicted how metabolic pathways influence different immune cell subsets in both health and disease as well as how genes, transcripts, and proteins interact with these pathways.

La Tesis Doctoral tiene como principal objetivo estudiar y evaluar los distintos enfoques quirúrgicos disponibles actualmente en la corrección del astigmatismo leve en la cirugía implantorrefractivo a través de lente fáquica ICL. En ella se discuten y se enfrentan el manejo incisional, a través de incisiones corneales periféricas relajantes realizadas en el meridiano curvo topográfico, y el implante de lentes tóricas. A su vez, los objetivos secundarios persiguen responder a la pregunta principal de investigación con un mayor rigor científico, dando soporte técnico sobre el análisis vectorial en el reporte de datos de astigmatismo y ahondar en aspectos hasta ahora no tratados en la bibliografía científica en relación al manejo incisional del astigmatismo. En concreto se estudia la arquitectura incisional de la herida corneal provocada por incisiones astigmáticas frente a la incisión quirúrgica principal, así como el efecto astigmáticos de incisiones realizadas con láser de femtosegundo frente a la técnica manual. Las conclusiones generales de la Tesis se pueden resumir en que el manejo de los astigmatismos leves es más eficaz con el implante de lentes tóricas en detrimento del enfoque incisional. Estos resultados están determinados en su mayor parte por la baja reproducibilidad del efecto astigmático generado por las incisiones corneales relajantes.

Background & aims: It has been reported that specific killer-cell immunoglobulin-like receptors (KIRs) and HLA genotype combinations, such as KIR2DS4/HLA-C1 with presence of KIRDL2 or KIRDL3, homozygous KIRDL3/ HLA-C1 and KIR3DL1/≥2HLA-Bw4, are strongly associated with the lack of active infection and seroconversion after exposition to hepatitis C virus (HCV). Objective: To determine whether these KIR-HLA combinations are relevant factors involved in that phenotype. Patients and methods: In this retrospective case-control study, genotype data from a genome-wide association study previously performed on low susceptibility to HCV-infection carried out on 27 high-risk HCV-eronegative (HRSN) individuals and 743 chronically infected (CI) subjects were used. HLA alleles were imputed using R package HIBAG v1.2223 and KIR genotypes were imputed using the online resource KIR*IMP v1.2.0. Results: It was possible to successfully impute at least one KIR-HLA genotype combination previously associated with the lack of infection and seroconversion after exposition to HCV in a total of 23 (85.2%) HRSN individuals and in 650 (87.5%) CI subjects. No KIR-HLA genotype combination analyzed was related to the HRSN condition. Conclusions: Our results suggest that those KIR-HLA genotype combinations are not relevant factors involved in the lack of infection and seroconversion after exposition to HCV. More studies will be needed to completely understand this phenotype.

La encefalomielitis autoinmune experimental (EAE), el modelo preclínico de esclerosis múltiple, se desencadena por células T efectoras específicas de mielina que se activan en la periferia y migran al sistema nervioso central (SNC), donde se reactivan e inducen la infiltración masiva de linfocitos T CD4+ y CD8+, células B, macrófagos y células dendríticas cuyos mediadores solubles, como las citoquinas proinflamatorias, dañan la mielina y provocan daño axonal. La forma clínica más común de EM es la remitente-recurrente (RR), caracterizada por episodios neuroinflamatorios seguidos de recuperación parcial o total del déficit neurológico. El tratamiento de primera línea para las recaídas de la EMRR consiste en una dosis alta de glucocorticoides, especialmente metilprednisolona, durante 3-5 días consecutivos. A pesar de que la melatonina mejora la gravedad de la EAE al modular las respuestas encefalitogénicas y supresoras de las células T, su mecanismo de acción aún no se ha dilucidado en detalle. Por lo tanto, los objetivos de este estudio fueron analizar los efectos de la melatonina en el primado periférico de las células T, su migración al SNC y su posterior reactivación, así como evaluar el efecto del tratamiento combinado con melatonina y metilprednisolona sobre la respuesta neuroinflamatoria asociada al desarrollo de EAE. Para ello, se indujo EAE en ratones hembras para analizar la frecuencia y/o expresión de moléculas coestimuladoras/coinhibidoras implicadas en la sinapsis inmune, moléculas de adhesión y ligandos/receptores de quimioquinas en las diferentes poblaciones inmunes involucradas en la inmunopatología de la EAE, tanto en los ganglios linfáticos inguinales y periaórticos, como en el SNC a lo largo de la enfermedad, además de analizar la integridad de la barrera hematoencefálica (BHE), los niveles de expresión de BDNF y de GFAP. Adicionalmente, se cuantificó el perfil efector/regulador de las poblaciones infiltrantes en el SNC tras el tratamiento combinado

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of unknown etiology characterized by infiltration of encephalitogenic cells in the central nervous system (CNS) resulting in the presence of multifocal areas of demyelination leading to neurodegeneration. The infiltrated immune cells population is composed mainly of effector CD4+ and CD8+ T lymphocytes, B cells, macrophages, and dendritic cells that secrete pro-inflammatory factors that eventually damage myelin leading to axonal damage. The most common clinical form of MS is relapsing-remitting (RR), characterized by neuroinflammatory episodes followed by partial or total recovery of neurological deficits. The first-line treatment for RRMS relapses is a high dose of glucocorticoids, especially methylprednisolone, for three to five consecutive days. Several studies have reported the beneficial effects of melatonin in the context of neuroinflammation associated with MS or experimental autoimmune encephalomyelitis (EAE), the preclinical model for MS. Therefore, the objective of this study was to evaluate the effect of the combined treatment of melatonin and methylprednisolone on the neuroinflammatory response associated with the EAE development. This study shows for the first time the protective synergistic effect of co-treatment with melatonin and methylprednisolone on reducing the severity of EAE by decreasing CD4 lymphocytes, B cells, macrophages and dendritic cells in the CNS, as well as modulating the population of infiltrated T and B cells toward regulatory phenotypes to the detriment of pro-inflammatory effector functions. In addition to the potentiation of the protective role of methylprednisolone, treatment with melatonin from the clinical onset of EAE improves the natural course of the EAE and the response to a subsequent treatment with methylprednisolone in a later relapse of the disease, pointing melatonin as potential therapeutic tool in combination with methylprednisolone for the treatment

The prevalence of obesity is increasingly widespread, resembling a global epidemic. Lifestyle changes, such as consumption of high-energy-dense diets and physical inactivity, are major contributors to obesity. Common features of this metabolic pathology involve an imbalance in lipid and glucose homeostasis including dyslipidemia, insulin resistance and adipose tissue dysfunction. Moreover, the importance of the gut microbiota in the development and susceptibility to obesity has recently been highlighted. In recent years, new strategies based on the use of functional foods, in particular bioactive peptides, have been proposed to counteract obesity outcomes. In this context, the present study examines the effects of a lupin protein hydrolysate (LPH) on obesity, dyslipidemia and gut dysbiosis in mice fed a high-fat diet (HFD). After 12 weeks of LPH treatment, mice gained less weight and showed decreased adipose dysfunction compared to the HFD-fed group. HFD-induced dyslipidemia (increased triglycerides, cholesterol and LDL concentration) and insulin resistance were both counteracted by LPH consumption. Discriminant analysis differentially distributed LPH-treated mice compared to non-treated mice. HFD reduced gut ecological parameters, promoted the blooming of deleterious taxa and reduced the abundance of commensal members. Some of these changes were corrected in the LPH group. Finally, correlation analysis suggested that changes in this microbial population could be responsible for the improvement in obesity outcomes. In conclusion, this is the first study to show the effect of LPH on improving weight gain, adiposopathy and gut dysbiosis in the context of diet-induced obesity, pointing to the therapeutic potential of bioactive peptides in metabolic diseases.

Tissue engineering (TE) demands scaffolds that have the necessary resistance to withstand the mechanical stresses once implanted in our body, as well as excellent biocompatibility. Hydrogels are postulated as interesting materials for this purpose, especially those made from biopolymers. In this study, the microstructure and rheological performance, as well as functional and biological properties of chitosan and collagen hydrogels (CH/CG) crosslinked with different coupling agents, both natural such as d-Fructose (F), genipin (G) and transglutaminase (T) and synthetic, using a combination of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with N-hydroxysuccinimide (EDC/NHS) will be assessed. FTIR tests were carried out to determine if the proposed crosslinking reactions for each crosslinking agent occurred as expected, obtaining positive results in this aspect. Regarding the characterization of the properties of each system, two main trends were observed, from which it could be established that crosslinking with G and EDC-NHS turned out to be more effective and beneficial than with the other two crosslinking agents, producing significant improvements with respect to the base CH/CG hydrogel. In addition, in vitro tests demonstrated the potential application in TE of these systems, especially for those crosslinked with G, T and EDC-NHS.

Malnutrition refers to a person’s status as under- or overnourished, and it is usually associated with an inflammation status, which can subsequently imply a different health status, as the risk of infection is increased, along with a deterioration of the immune system. Children’s immune systems are generally more susceptible to problems than adults. In the situation of malnutrition, because malnourished children’s immune systems are compromised, they are more likely to die. However, little is known about the underlying mechanism of altered immune functioning and how it relates to starvation. Nutritional interventions have been reported as cost-effective strategies to prevent or treat the development of malnourishment, considering the link between food intake and health, especially in children, and also the susceptibility of this population to diseases and how their health status during childhood might affect their long-term physiological growth. The ingestion of specific nutrients (e.g., vitamins or oligoelements) has been reported to contribute to the proper functioning of children’s immune systems. In this review, we aim to describe the basis of malnutrition and how this is linked to the immune system, considering the role of nutrients in the modulation of the immune system and the risk of infection that can occur in these situations in children, as well as to identify nutritional interventions to improve their health.

Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD). In line with those notions, different therapeutic approaches have been tested to enhance or impair the concentration and role of the different DC subsets. The blockade of inhibitory pathways to promote DCs or DC-based vaccines have been successfully assessed in cancer, whereas the targeting of DCs to inhibit their functionality has proved to be favorable in IBD. In this review, we (a) described the general role of DCs, (b) explained the DC subsets and their role in immunogenicity, (c) analyzed the role of DCs in cancer and therapeutic approaches to promote immunogenic DCs and (d) analyzed the role of DCs in IBD and therapeutic approaches to reduced DC-induced inflammation. Therefore, we aimed to highlight the “yin-yang” role of DCs to improve the understand of this type of cells in disease progression.

In the month of March in the year 2020, an alarming pandemic triggered by the SARS CoV-2 virus, which leads to the development of the notorious COVID-19 disease, was officially declared. The consequences of this coronavirus have been utterly devastating, resulting in the unfortunate demise of countless individuals due to the severe deterioration experienced both in the pulmonary as well as systemic aspects of their health.

Cancer is a complex disease that, despite advances in treatment and the greater understanding of the tumor biology until today, continues to be a prevalent and lethal disease. Chemotherapy, radiotherapy, and surgery are the conventional treatments, which have increased the survival for cancer patients. However, the complexity of this disease together with the persistent problems due to tumor progression and recurrence, drug resistance, or side effects of therapy make it necessary to explore new strategies that address the challenges to obtain a positive response. One important point is that tumor cells can interact with the microenvironment, promoting proliferation, dissemination, and immune evasion. Therefore, immunotherapy has emerged as a novel therapy based on the modulation of the immune system for combating cancer, as reflected in the promising results both in preclinical studies and clinical trials obtained. In order to enhance the immune response, the combination of immunotherapy with nanoparticles has been conducted, improving the access of immune cells to the tumor, antigen presentation, as well as the induction of persistent immune responses. Therefore, nanomedicine holds an enormous potential to enhance the efficacy of cancer immunotherapy. Here, we review the most recent advances in specific molecular and cellular immunotherapy and in nano immunotherapy against cancer in the light of the latest published preclinical studies and clinical trials.

La generalización del tratamiento antirretroviral (TAR) ha supuesto una importante disminución de la morbi-mortalidad de los pacientes con infección por el virus de la inmunodeficiencia humana (VIH). Con la cronificación de la enfermedad y disminución de eventos infecciosos oportunistas, han emergido las complicaciones cardiovasculares. Los hallazgos más frecuentes son la hipertensión arterial pulmonar (HTP), la disfunción sistólica y diastólica (DD) del ventrículo izquierdo (VI) pero los mecanismos no están del todo claros. Sin duda, el papel de la ecocardiografía en la detección de alteraciones estructurales es crucial. Además de la fracción de eyección de ventrículo izquierdo (FEVI), cada vez hay más evidencia del posible papel de los parámetros de deformación miocárdica (strain) en la detección precoz de la disfunción sistólica del VI y derecho (VD). Desafortunadamente, la mayoría de los estudios publicados utilizando este parámetro se focalizan en la comparación del strain entre pacientes con y sin VIH, pero son pocos los estudio que definen la disfunción sistólica con esta técnica utilizando claros puntos de corte y los factores relacionados con esta alteración subclínica. En la última década, son varias las publicaciones que comunican variaciones en distintos biomarcadores en la población VIH como el péptido natriurético cerebral (NT-proBNP) y la troponina T ultrasensible (TnTus). Por todo ello, nuestros objetivos son: 1) Conocer la prevalencia de disfunción sistólica, mediante FEVI y strain, y DD de VI en una cohorte de pacientes asintomáticos y sin cardiopatía conocida con infección por el VIH y los factores asociados a la misma. 2) Describir la prevalencia de HTP y otras alteraciones ecocardiográficas en nuestra muestra. 3) Relacionar estos datos ecocardiográficos con biomarcadores. MÉTODOS Se realiza un estudio transversal en el que se incluyen pacientes con VIH con las características descritas a los que se les realiza un ecocardiograma transtorácico par

Introducción: El melanoma cutáneo es un tumor maligno cuya incidencia se ha ido incrementando en las últimas décadas a lo largo de todo el mundo. Aproximadamente el 40% de los melanomas cutáneos se diagnostican en mayores de 65 años y mientas que en los pacientes menores de 65 la mortalidad por melanoma se ha ido reduciendo con el paso del tiempo, en los pacientes mayores ha sucedido lo contrario. Todo esto, asociado al aumento en la esperanza de vida que la población va a experimentar en las próximas décadas, va a hacer que esta patología se convierta en un problema importante de salud pública. Métodos: Estudio retrospectivo de casos incidentes de melanoma entre 2007-2022 en el área sur de Sevilla, España. Se establecieron dos grupos de pacientes según su edad: <65 y ?65 años. La recolección de datos se obtuvo a través de la historia clínica de los pacientes con el objetivo de identificar las características diferenciales clínicas, histológicas y pronósticas del melanoma cutáneo primario en los pacientes mayores de 65 años en comparación con los menores, con la finalidad de averiguar si existen variaciones relacionadas con la edad en cuanto al manejo quirúrgico y médico de estos pacientes que suelen asociar comorbilidades y fragilidad. Resultados: En el periodo de investigación del estudio el 33% de los pacientes con melanoma cutáneo primario fueron mayores de 65 años. La incidencia de este tumor en este subgrupo de edad ha ido aumentando desde un 15,38% en 2007 hasta un 34,78% en 2022. La población más joven presentó 2,96 veces (IC95% 1,86-4,73; p<0,05) más riesgo de quemadura solar en su infancia y 16,5 veces (IC95% 2,23-122,23; p<0,05) más riesgo de uso de cabinas UVA frente a la población más anciana. Los melanomas localizados en cabeza y cuello fueron más frecuentes en ?65 años (37,8% vs 14,9%; p<0,001). El subtipo histológico más frecuente en ambos grupos de edad fue el MES (43,4% en ?65 años y 74,7% en <65 años), pero su frecuencia descendió considerablement

Este capítulo de libro se basa en el uso del podcasting como herramienta de innovación docente, y la evaluación de los conocimientos adquiridos por el alumnado de la asignatura de Métodos Instrumentales Cuantitativos que se imparte en tercer curso del Grado en Bioquímica por la Universidad de Sevilla y la Universidad de Málaga. Los podcasts fueron almacenados y distribuidos a través de la plataforma Spotify for Podcasters, donde se puede reproducir, descargar y compartir los audios de todo el contenido digital multimedia generado en la asignatura. Posteriormente, el conocimiento adquirido por el alumnado fue evaluado a diferentes intervalos de tiempo mediante la realización de cuestionarios con Wooclap, una herramienta que permite la evaluación del aprendizaje de distinta forma (test, preguntas abiertas, encuesta, etc.). Se realizó también un análisis de los resultados obtenidos en función del sexo del alumnado como variable. Toda la metodología empleada en este trabajo se basa en el uso de las Tecnologías de la Información y la Comunicación (TIC) con el propósito de hacer el proceso de enseñanza más dinámico y pedagógico, aportando un enfoque innovador en la transferencia del conocimiento en la Universidad de Sevilla. Finalmente, se ha valorado el grado de satisfacción de la utilidad de los podcasts a través de un formulario de Google de carácter anónimo y voluntario. Los resultados obtenidos de la aplicación de esta metodología demuestran: i) un aumento del porcentaje de conocimientos adquiridos comparado con el modelo de enseñanza tradicional (% de conocimientos adquiridos vs % de conocimientos adquiridos con recursos TICs, p= 0,0497); ii) una mayor diferencia significativa en el caso de las mujeres entre el porcentaje de conocimientos que los estudiantes poseían en el cuestionario inicial y después de escuchar el podcast en el cuestionario final (n= 26, % de conocimientos iniciales vs % de conocimientos adquiridos con recursos TICs, p< 0,0001) con respecto a los

The HIV attacks the immune system provoking an infection that is considered a global health challenge. Despite antiretroviral treatments being effective in reducing the plasma viral load in the blood to undetectable levels in people living with HIV (PLWH), the disease is not cured and has become chronic. This happens because of the existence of anatomical and cellular viral reservoirs, mainly located in the lymph nodes and gastrointestinal tract, which are composed of infected CD4+ T cells with a resting memory phenotype and inaccessible to antiretroviral therapy. Herein, a new therapeutic strategy based on nanotechnology is presented. Different combinations of antiretroviral drugs (bictegravir/tenofovir/emtricitabine and nevirapine/tenofovir/emtricitabine) and toll-like receptor agonists were encapsulated into metal–organic frameworks (MOFs) PCN-224 and ZIF-8. The encapsulation efficiencies of all the drugs, as well as their release rate from the carriers, were measured. In vitro studies about the cell viability, the hemocompatibility, and the platelet aggregation of the MOFs were carried out. Epifluorescence microscopy assays confirmed the ability of ZIF-8 to target a carboxyfluorescein probe inside HeLa cell lines and PBMCs. These results pave the way for the use of these structures to eliminate latent HIV reservoirs from anatomical compartments through the activation of innate immune cells, and a higher efficacy of the triplet combinations of antiretroviral drugs.

Oxidative stress plays a crucial role in neurodegenerative diseases like Parkinson's and Alzheimer's. Studies indicate the relationship between oxidative stress and the brain damage caused by a high-fat diet. It is previously found that a lupin protein hydrolysate (LPH) has antioxidant effects on human leukocytes, as well as on the plasma and liver of Western diet (WD)-fed ApoE-/- mice. Additionally, LPH shows anxiolytic effects in these mice. Given the connection between oxidative stress and anxiety, this study aimed to investigate the antioxidant effects of LPH on the brain of WD-fed ApoE-/- mice. LPH (100 mg kg-1) or a vehicle is administered daily for 12 weeks. Peptide analysis of LPH identified 101 amino acid sequences (36.33%) with antioxidant motifs. Treatment with LPH palliated the decrease in total antioxidant activity caused by WD ingestion and regulated the nitric oxide synthesis pathway in the brain of the animals. Furthermore, LPH increased cerebral glutathione levels and the activity of catalase and glutathione reductase antioxidant enzymes and reduced the 8-hydroxy-2'-deoxyguanosine levels, a DNA damage marker. These findings, for the first time, highlight the antioxidant activity of LPH in the brain. This hydrolysate could potentially be used in future nutraceutical therapies for neurodegenerative diseases.

La esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa actualmente incurable que, en el momento del diagnóstico, establece una esperanza de vida de entre 3 y 5 años. Con la evolución de la enfermedad, las motoneuronas terminan degenerando y provocando síntomas severos de debilidad muscular característicos de esta neuropatía que finalmente termina extendiéndose a los músculos de control involuntario. Entre los mecanismos moleculares alterados y las características patológicas observadas en la enfermedad se encuentran descritas vías de estrés oxidativo y de excitotoxicidad, metabolismo de ARN, disfunción mitocondrial o proteasomal, agregación citoplásmica de TDP-43, autofagia o neuroinflamación crónica mediada por microglía. Conforme afloran los hallazgos acerca de esta neuropatología, se hace patente la idea de que pueda estar provocada por un solo mecanismo desencadenante. En este contexto, la neuroinflamación, a pesar de haber tomado creciente interés en los últimos años en enfermedades neurodegenerativas, aún no está presente como diana en las estrategias de intervención sobre la ELA. En este contexto inflamatorio, la célula inmune residente del sistema nervioso central (SNC), la microglía, juega un papel relevante en la modulación y desarrollo de la neuroinflamación. Estas células protagonizan las acciones del sistema inmune en el SNC, conduciendo las reacciones de inflamación cuando ocurre un daño, con el objetivo final de volver a un estado de homeostasis. Desafortunadamente, cuando esta comunicación molecular se ve impedida, prolongada en el tiempo o es errática, la microglía puede adoptar funciones neurotóxicas, con un significativo impacto en la fisiología del resto de células del SNC. Numerosas vías de señalización, donde generalmente participan proteínas quinasas, surgen como dianas interesantes de este escenario. MAPK/MAK/MRK overlapping kinase (MOK) es una serina/treonina quinasa poco estudiada que recientemente ha despertado interés

Breast cancer (BC) continues to be the most diagnosed tumor in women and a very heterogeneous disease both inter- and intratumoral, mainly given by the variety of molecular profiles with different biological and clinical characteristics. Despite the advancements in early detection and therapeutic strategies, the survival rate is low in patients who develop metastatic disease. Therefore, it is mandatory to explore new approaches to achieve better responses. In this regard, immunotherapy arose as a promising alternative to conventional treatments due to its ability to modulate the immune system, which may play a dual role in this disease since the relationship between the immune system and BC cells depends on several factors: the tumor histology and size, as well as the involvement of lymph nodes, immune cells, and molecules that are part of the tumor microenvironment. Particularly, myeloid-derived suppressor cell (MDSC) expansion is one of the major immunosuppressive mechanisms used by breast tumors since it has been associated with worse clinical stage, metastatic burden, and poor efficacy of immunotherapies. This review focuses on the new immunotherapies in BC in the last five years. Additionally, the role of MDSC as a therapeutic target in breast cancer will be described.

El agua es un elemento básico en la fisiología de los seres vivos. A escala celular, su transporte se encuentra facilitado por las acuaporinas (AQPs), una familia de proteínas integrales de membrana ubicuamente distribuidas por los distintos sistemas del organismo. En el Sistema Nervioso Central (SNC), acuaporina-4 (AQP4) es la AQP más ampliamente expresada y juega un papel clave en la homeostasis de los distintos líquidos que fluyen en el sistema. No obstante, pocos estudios han abordado el papel de esta proteína durante el desarrollo. En este trabajo, hemos caracterizado el curso de aparición de la proteína AQP4 durante el desarrollo postnatal del SNC, destacando dos regiones que manifestaron perfiles de expresión singulares: el acueducto cerebral y el cuerpo calloso. Profundizando en el sentido fisiológico de estas observaciones, utilizamos el ratón transgénico con deleción de AQP4 (AQP4-KO) y evaluamos parámetros relacionados con el neurodesarrollo postnatal en ambas regiones. Mediante varias aproximaciones, determinamos la existencia de defectos asociados a la diferenciación y desarrollo de estructuras ciliares en las células ependimarias del acueducto cerebral del ratón AQP4-KO. Asimismo, en el cuerpo calloso de este animal, identificamos déficits en la abundancia y maduración de oligodendrocitos, así como en la formación de mielina. Interesantemente, el análisis de ambas regiones nos hizo hallar un subtipo microglial CD11c+ que, con una huella transcripcional asociada al neurodesarrollo, mostró una presencia exclusiva en el animal AQP4- KO durante el estadio postnatal estudiado. Por último, para analizar la posible influencia de esta población microglial, evaluamos el efecto que su depleción (realizada por vía farmacológica con el compuesto PLX5622) generó en las regiones de interés, indicando un papel relevante en el desarrollo del tejido ependimario. En conclusión, este trabajo apoya la importancia de la expresión de AQP4 en el desarrollo temprano del SNC, Water transport facilitated by aquaporins (AQPs) is an indispensable mechanism to achieve fluid homeostasis in the different compartments of the organism. In the central nervous system (CNS), aquaporin-4 (AQP4) is the most abundantly expressed AQP and, given its localised pattern in the border regions, it is considered a determining element in the aqueous exchange between the different fluids of the system. In recent years, this property has been especially reinforced by the proposal of the existence of the glymphatic system, which highlights AQP4 as a key component in the establishment of a convective flow linked to the clearance of compounds in the brain parenchyma. This new scenario has prompted numerous studies focused on understanding how brain clearance of substances occurs and developing new clinical strategies to eliminate neurotoxic protein accumulations, a plausible therapy against neurodegenerative diseases such as Alzheimer's disease. A major role in these approaches has been played by the characterisation of the AQP4 knockout mouse (AQP4-KO), a model that, in addition to presenting a greater susceptibility to develop symptoms compatible with Alzheimer's disease, has been associated with a predisposition to suffer pathologies associated with early CNS development, such as congenital hydrocephalus. Postnatal CNS development is one of the major phases of activation of processes such as proliferation, differentiation and changes in cellular and molecular components of the parenchyma. These involve significant water movement and osmotic imbalances in which the role of AQP4 has not been studied in detail. In this work, we provide a better understanding of the distribution of AQP4 during postnatal murine CNS development and its contribution to the development of different periventricular neural tissues. To this end, we first sought to characterise when and where AQP4 expression arises in the CNS, assessing the levels and distribution of its gene expression. Fr

Según la Organización Mundial de la Salud (WHO) las enfermedades crónicas no transmisibles (ECNT) como las enfermedades cardiovasculares, cáncer, obesidad, enfermedades respiratorias crónicas, diabetes e hipertensión, se cobran la vida de 41 millones de personas todos los años, por lo que se hace necesaria la búsqueda de nuevos compuestos bioactivos alimentarios como alternativa eficaz al tratamiento farmacológico, pudiendo actuar como inmunomodulador de las enfermedades relacionadas con estados crónicos oxidativos e inflamatorios. En este trabajo se ha obtenido un hidrolizado proteico a partir de semillas de chía (Salvia hispanica L.), considerada hoy en día un superalimento, y de la que existen múltiples evidencias científicas sobre sus propiedades nutricionales y funcionales, así como que, la hidrólisis enzimática de sus proteínas genera péptidos bioactivos con efectos positivos en la salud. En este trabajo, se han demostrado las propiedades tecnofuncionales de un hidrolizado de chía obtenido con la enzima Alcalase, interesantes para su incorporación en diferentes matrices y productos de la industria alimentaria. Por otra parte, se ha secuenciado, identificado y estudiado su biodisponibilidad en un sistema de absorción intestinal tipo transwell utilizando la línea celular Caco-2, mediante el estudio del peptidoma de los hidrolizados proteicos de chía original y tras la absorción intestinal, así como el estudio in silico de su potencial bioactivo para la selección de los péptidos responsables de dicha actividad. Por último, y mediante ensayos in vitro en monocitos humanos primarios, se ha demostrado que el hidrolizado proteico de chía, disminuyó el estrés oxidativo, la expresión génica y liberación de citoquinas proinflamatorias, aumentó la expresión génica y liberación de marcadores antiinflamatorios favoreciendo la polarización de los macrófagos derivados de monocitos hacia el fenotipo antiinflamatorio M2, pudiendo ser considerado por tanto, un candidato potenci

Introducción: La EM se trata de una enfermedad inmunológica, inflamatoria desmielinizante y degenerativa del SNC, caracterizada por etiología multifactorial y compleja. En ella se produce una inflamación y desmielinización del SNC, a consecuencia de una respuesta equivocada de tipo inmune y atípica. Esta enfermedad ocasiona en un primer momento desmielinización, así como, en un grado variable, un daño axonal, pero lo más probable es que se produzca un trastorno neurológico, que afecta solo al SNC. Esto ocasiona que se produzcan los déficits neurológicos de tipo permanente, que están asociados a la EM. La melatonina está relacionada con la inducción y el mantenimiento del sueño. En los pacientes con EM se ha visto que, cerca de la mitad de ellos, sufre anomalías del sueño. Objetivos: Nuestro objetivo es estudiar la relación que existe entre la calidad del sueño de pacientes afectados con EM y la producción de melatonina, y correlacionar los indicadores clínicos generales de estos pacientes, especialmente los relacionados con la fatiga, estado de ánimo y función cognitiva con la calidad del sueño y los niveles de melatonina. Método: Nuestro estudio está diseñado utilizando el método es prospectivo, de centro único, abierto, observacional, de cohortes en pacientes que están diagnosticados de EM antes de iniciar terapia con inmunomoduladores. Se han incluido 30 pacientes con EM diagnosticado según criterios de McDonald 2017 y sin tratamiento inmunomodulador, 15 pacientes con trastornos del sueño y 15 pacientes sin trastornos de sueño. Además, se incluyó un grupo control constituido por 30 sujetos sanos, los cuales estaban pareados por sexo y edad con los pacientes. Se valoraron otras escalas de discapacidad (9HPT, EuroQol 5-D y EQ-5D). Posteriormente, se procedió a recoger las muestras de orina de los pacientes y los controles. Una vez reunidas todas las orinas, se trasladaron al Laboratorio de NeuroInmuno Endocrinología Molecular del IBiS en un contenedor que preservar

Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development1,2. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release2. The increased number of candidate genes at the identified loci helped to map three major biological pathways that are involved in susceptibility and severity: viral entry, airway defence in mucus and type I interferon. (extract)

Background: Sulforaphane (SFN) is an isothiocyanate of vegetable origin with potent antioxidant and immunomodulatory properties. The characterization of its pleiotropic activity in human dendritic cells (DCs) is poorly summarized. The aim of this work was to study the immunomodulatory power of SFN in response to an inflammatory microenvironment on human monocyte-derived DCs (moDCs). Methods: We studied the immunological response induced by SFN. Apoptosis and autophagy assays were performed using flow cytometry on moDCs and a cancer cell line (THP-1). These included moDC maturation, lymphocyte proliferation and cytokine production under different experimental conditions. We investigated whether these results were associated with an inflammatory microenvironment induced by lipopolysaccharides (LPSs). Results: Our results demonstrated that SFN could interact with moDCs, significantly reducing the autophagy process and enhancing apoptosis similarly to cancer cell line THP-1 cells in a chronic inflammatory microenvironment. Under chronic inflammation, SFN modulated the phenotypical characteristics of moDCs, reducing the expression of all markers (CD80, CD83, CD86, HLA-DR and PD-L1). SFN significantly reduced the Th2 proliferative response, with a decrease in the IL-9 and IL-13 levels. Although we did not observe any changes in the regulatory proliferative response, we noted an increase in the IL-10 levels. Conclusions: These findings demonstrate that SFN exerts protective effects against LPS-induced inflammation via the modulation of moDCs/T cells towards a regulatory profile. SFN may be a potential candidate for the treatment of pathologies with an inflammatory profile.

Dipeptidyl peptidase IV (DPP-IV) is considered a key target for the diabetes treatment, since it is involved in glucose metabolism. Although lupin protein consumption shown hypoglycemic activity, there is no evidence of its effect on DPP-IV activity. This study demonstrates that a lupin protein hydrolysate (LPH), obtained by hydrolysis with Alcalase, exerts anti-diabetic activity by modulating DPP-IV activity. In fact, LPH decreased DPP-IV activity in a cell-free and cell-based system. Contextually, Caco-2 cells were employed to identify LPH peptides that can be intestinally trans-epithelial transported. Notably, 141 different intestinally transported LPH sequences were identified using nano- and ultra-chromatography coupled to mass spectrometry. Hence, it was demonstrated that LPH modulated the glycemic response and the glucose concentration in mice, by inhibiting the DPP-IV. Finally, a beverage containing 1 g of LPH decreased DPP-IV activity and glucose levels in humans.

Background: New challenges in our society are appearing following the emergence of antibiotic-resistant mi- croorganisms and the concerns about the use of antibiotics. Furthermore, food spoilage due to microorganisms leads to food waste of around 1.3 billion tons each year. Bioactive peptides obtained from food proteins, released by enzymatic hydrolysis or fermentation, can be employed as a natural alternative to antibiotics and as pre- servative agents, due to their ability to inhibit the growth of several microorganisms. Plant protein use in the food industry is increasing over animal protein, due to the environmental and animal welfare concerns of the population. Considering the concerns about the use antibiotics, their exploitation as a source of antimicrobial peptides is gaining interest in recent years. Scope and approach: This review aims to summarize the published literature on protein hydrolysates as a source of antimicrobial peptides, obtained by enzymatic hydrolysis or fermentation of plants, their mechanisms, and the use in the food industry by producing fortified products or edible coatings. Key findings and conclusions: Antibacterial and antifungal plant peptides obtained by enzymatic hydrolysis are studied to a larger extent that antiviral peptides but further research concerning identification and applicability must be done. The results published show promising uses in the food industry in many areas such as fortification of foods or active packaging with dual bioactivity, related to the antimicrobial activity – avoiding food spoilage and antimicrobial resistance.

Hemp is the term commonly used to refer to the variety of Cannabis sativa L. cultivated for industrial purposes. The seeds have gained interest in recent years as functional foods due to their nutritional composition and high content of protein and bioactive compounds. In this study, ten hemp protein hydrolysates (HPHs) were obtained by enzymatic hydrolysis with Alcalase and Flavourzyme from hemp protein isolate (HPI) and their antioxidant properties (DPPH radical scavenging activity, beta-carotene activity and ferric ion reducing antioxidant power (FRAP)) were evaluated. Shorter peptide sequences, mainly obtained with Flavourzyme, were found to react with free radicals more easily. The peptidome of all the hydrolysates was characterized, identifying, and quantifying the peptides. Furthermore, 19 unique peptides were assessed by in silico tools to hypothesize those that could be responsible of the bioactivity reported for the hydrolysates. From the identified peptides, based on the molecular features and the predictions, the peptides KNAIYTPH, EERPGHF, and KNGMMAPH, among others, are proposed to be highly contributing to the antioxidant activity of the hydrolysates.

Some HIV controllers experience immunologic progression with CD4+ T cell decline. We aimed to identify genetic factors associated with CD4+ T cell lost in HIV controllers. A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No SNP or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual GWAS or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p = 0.005; OR = 1.70], rs59440261 [p = 0.003; OR = 1.78]), MICA (rs112243036 [p = 0.011; OR = 1.45]), and PSORS1C1 loci (rs3815087 [p = 0.017; OR = 1.39]) showed nominal association with this phenotype. Genetic factors associated with the long-term HIV controllers without risk of immunologic progression are those previously related to the overall HIV controller phenotype.

The Mediterranean diet (MD) has beneficial effects on human health, which is evidenced by the observation of lower incidence rates of chronic diseases in Mediterranean countries. The MD dietary pattern is rich in antioxidants, such as melatonin, which is a hormone produced mainly by the pineal gland and controls several circadian rhythms. Additionally, melatonin is found in foods, such as fruit and vegetables. The purpose of this systematic review was to assess the melatonin content in Mediterranean foods and to evaluate the influence of the MD on melatonin levels in both humans and model organisms. A comprehensive search was conducted in four databases (PubMed, Scopus, Cochrane Library and Web of Science) and data were extracted. A total of 31 records were chosen. MD-related foods, such as tomatoes, olive oil, red wine, beer, nuts, and vegetables, showed high melatonin contents. The consumption of specific MD foods increases melatonin levels and improves the antioxidant status in plasma.

Aims: Microglia survey the brain environment by sensing alarm signals to provide the first line of defense against injury or infection after which they acquire an activated phenotype, but they also respond to chemical signals sent from brain mast cells, sentinels of the immune system, when these are degranulated in response to noxious agents. Nevertheless, excessive microglia activation damages the surrounding healthy neural tissue causing progressive loss of neurons and inducing chronic inflammation. Thus, it would be of intense interest the development and application of agents which prevent mast cell mediator release and inhibit the actions of such mediators once released on microglia. Main methods: Fluorescence measurements of fura-2 and quinacrine were used to measure intracellular Ca2+ signaling and exocytotic vesicle fusion in resting and activated microglia. Key findings: We show that treatment of microglia with a cocktail of mast cell mediators induces microglia activation, phagocytosis, and exocytosis, and reveal by the first-time microglia undergo a phase of vesicular acidification just before the exocytotic fusion occurs. This acidification is an important process for vesicular maturation and contributes with ~25 % to the content that the vesicle can store and later release by exocytosis. Pre-incubation with ketotifen, a mast cell stabilizer and H1R antagonist completely abolished histaminemediated calcium signaling and acidification of microglial organelles, and concomitantly reduced the discharge of vesicle contents. Significance: These results highlight a key role for vesicle acidification in microglial physiology and provide a potential therapeutic target for diseases related to mast cell and microglia-mediated neuroinflammation.

A gelatin-based hydrogel was infiltrated and degraded-released in two different titanium foams with porosities of 30 and 60 vol.% (Ti30 and Ti60 foams) and fabricated by the space holder technique to evaluate its potential to act as an innovative, alternative, and localised method to introduce both active pharmaceutical ingredients, such as antibiotics and non-steroidal anti-inflammatory drugs, and growth factors, such as morphogens, required after bone-tissue replacement surgeries. In addition, the kinetic behaviour was studied for both infiltration and degradation-release processes. A higher infiltration rate was observed in the Ti60 foam. The maximum infiltration hydrogel was achieved for the Ti30 and Ti60 foams after 120 min and 75 min, respectively. Further, both processes followed a Lucas-Washburn theoretical behaviour, typical for the infiltration of a fluid by capillarity in porous channels. Regarding the subsequent degradation-release process, both systems showed similar exponential degradation performance, with the full release from Ti60 foam (80 min), versus 45 min for Ti30, due to the greater interconnected porosity open to the surface of the Ti60 foam in comparison with the Ti30 foam. In addition, the optimal biocompatibility of the hydrogel was confirmed, with the total absence of cytotoxicity and the promotion of cell growth in the fibroblast cells evaluated.

Alzheimer’s disease (AD) is the most common form of dementia. The physiopathology of AD is well described by the presence of two neuropathological features: amyloid plaques and tau neurofibrillary tangles. In the last decade, neuroinflammation and cellular stress have gained importance as key factors in the development and pathology of AD. Chronic cellular stress occurs in degenerating neurons. Stress Granules (SGs) are nonmembranous organelles formed as a response to stress, with a protective role; however, SGs have been noted to turn into pathological and neurotoxic features when stress is chronic, and they are related to an increased tau aggregation. On the other hand, correct lipid metabolism is essential to good function of the brain; apolipoproteins are highly associated with risk of AD, and impaired cholesterol efflux and lipid transport are associated with an increased risk of AD. In this review, we provide an insight into the relationship between cellular stress, SGs, protein aggregation, and lipid metabolism in AD.

The aim of this study was to analyze the possible nephroprotective effect of 3’,4’-dihydroxy phenylglycol (DHPG), a polyphenolic compound of extra virgin olive oil (EVOO), on renal lesions in an experimental model of type 1 diabetes. Rats were distributed as follows: healthy normoglycemic rats (NDR), diabetic rats treated with saline (DR), and DR treated with 0.5 mg/kg/day or 1 mg/kg/day of DHPG. DR showed a significantly higher serum and renal oxidative and nitrosative stress profile than NDR, as well as reduced prostacyclin production and renal damage (defined as urinary protein excretion, reduced creatinine clearance, increased glomerular volume, and increased glomerulosclerosis index). DHPG reduced the oxidative and nitrosative stress and increased prostacyclin production (a 59.2% reduction in DR and 34.7–7.8% reduction in DHPG-treated rats), as well as 38–56% reduction in urinary protein excretion and 22–46% reduction in glomerular morphological parameters (after the treatment with 0.5 or 1 mg/kg/day, respectively). Conclusions: DHPG administration to type 1-like diabetic rats exerts a nephroprotective effect probably due to the sum of its antioxidant (Pearson’s coefficient 0.68–0.74), antinitrosative (Pearson’s coefficient 0.83), and prostacyclin production regulator (Pearson’s coefficient 0.75) effects.

Background: Over the last two decades, the demand for meat-free food has increased for health, environmental, and animal welfare reasons. Thus, research on the value of vegetable compounds as beneficial agents for human health has gained much attention. In particular, great interest has been shown in protein hydrolysation since this food technology facilitates the release of encrypted peptides with biological activities. In this sense, during the last 10 years, the biological activities of Lupinus spp. protein hydrolysates (LPHs) have been extensively studied. Scope and approach: The aim of this review is to address all studies (in silico, in vitro, and in vivo) in which the biological activities (antioxidant, anti-inflammatory, etc.) of LPHs were described, both the whole hydrolysate and the derived peptides. Moreover, the physicochemical characteristics of LPH peptides are evaluated, and challenges and future perspectives for their fast application have been discussed. Key findings and conclusions: LPHs exert many important biological effects in both the in vitro and in vivo systems. The main activities of LPHs described are antioxidant, immunomodulatory, hypotensive, hypoglycemic, and hypolipidemic. These findings point to LPHs as a possible new nutraceutical for human health, capable of preventing or treating some chronic diseases such as diabetes, dyslipidemia, and atherosclerosis. Finally, the development of a new generation of nanonutraceuticals to improve the metabolic stability and bioactivity of LPHs has been discussed.

Nutraceuticals act as cellular and functional modulators, contributing to the homeostasis of physiological processes. In an inflammatory microenvironment, these functional foods can interact with the immune system by modulating or balancing the exacerbated proinflammatory response. In this process, immune cells, such as antigen-presenting cells (APCs), identify danger signals and, after interacting with T lymphocytes, induce a specific effector response. Moreover, this conditions their change of state with phenotypical and functional modifications from the resting state to the activated and effector state, supposing an increase in their energy requirements that affect their intracellular metabolism, with each immune cell showing a unique metabolic signature. Thus, nutraceuticals, such as polyphenols, vitamins, fatty acids, and sulforaphane, represent an active option to use therapeutically for health or the prevention of different pathologies, including obesity, metabolic syndrome, and diabetes. To regulate the inflammation associated with these pathologies, intervention in metabolic pathways through the modulation of metabolic energy with nutraceuticals is an attractive strategy that allows inducing important changes in cellular properties. Thus, we provide an overview of the link between metabolism, immune function, and nutraceuticals in chronic inflammatory processes associated with obesity and diabetes, paying particular attention to nutritional effects on APC and T cell immunometabolism, as well as the mechanisms required in the change in energetic pathways involved after their activation.

The immune-inflammatory, glucose homeostasis, and antioxidant response have a crucial role in the prevention of non-communicable chronic diseases, according to the World Health Organization (WHO). As people live longer in society, the lifestyle of human changes and the prevalence of age-related degenerative diseases and obesity is likewise rising quickly. One of the subfields of nutritional sciences, which covers the study of nutrients and other food ingredients with an emphasis on how they affect mammalian physiology, health, and behaviour, is nutritional biochemistry. Immunonutrition is a new and interdisciplinary field within Nutritional Biochemistry since it encompasses many elements of nutrition, immunity, inflammation, oxidation, and illnesses with an immunometabolic basis. One of the promising ingredients that are currently being assessed by scientists in terms of immunonutrition is food extracts.