Artículos (Bioquímica Médica y Biología Molecular e Inmunología)

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Systemic Inflammation and Malnutrition Define a High-Risk Phenotype in Chronic Limb-Threatening Ischemia
(MDPI, 2026) Luque Linero, Paula; Salamanca Bautista, María del Prado; Carmona Nimo, Eduardo; Arrobas Velilla, Teresa; Rivera de los Santos, Francisco José; Rico Corral, Miguel Ángel; Psicología Experimental; Medicina; Bioquímica Médica y Biología Molecular e Inmunología
Objective: This study aimed to evaluate the prognostic value of inflammatory biomarkers and their interaction with nutritional status for risk stratification in patients with chronic limb-threatening ischemia (CTLI). Material and Methods: This was a prospective, single-center observational cohort study including adult patients admitted with CTLI. Clinical outcomes included major amputation, major vascular events (MACE), and all-cause mortality. Multivariate logistic regression analyses were performed using two separate models, one including IL-6 and another including hsCRP, to avoid potential collinearity between biomarkers. Model discrimination was assessed using ROC curves, and Kaplan–Meier survival analyses were performed. Results: A total of 170 patients were included (mean age 72 ± 12 years; 74% male), with high cardiovascular risk and frequent malnutrition and sarcopenia. At 6 months, major amputations occurred in 35.3% of patients, MACE in 35%, and all-cause mortality in 32%. In multivariable analyses, malnutrition was the strongest independent predictor of the composite endpoint. IL-6 (OR 2.90, 95% CI 1.45–5.81; p = 0.003) and hsCRP values above the median (OR 4.22, 95% CI 2.04–8.72; p < 0.001) remained independently associated with adverse outcomes, together with age > 72 years. The hsCRP-based model showed slightly higher discriminative performance than the IL-6 model (AUC = 0.77 VS AUC = 0.75). Kaplan–Meier analyses demonstrated significantly reduced event-free survival in patients with elevated inflammatory biomarkers. Conclusions: In CTLI, systemic inflammation and nutritional status jointly identify patients at extremely high risk of adverse outcomes. hsCRP, given its availability, may be a practical tool for clinical risk stratification.
The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease
(BioMed Central, 2011-05-31) Antunez, Carmen; Boada, Mercè; González Pérez, Antonio; Gayán, Javier; Ramírez Lorca, Reposo; Marín, Juan; Sáez Ortega, María Loreto; Real Navarrete, Luis Miguel; Ruiz, Agustín; Fisiología Médica y Biofísica; Cirugía; Bioquímica Médica y Biología Molecular e Inmunología; Agencia IDEA; Alzheimer\'s Disease Neuroimaging Initiative (ADNI); CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM); Corporacion Tecnologica de Andalucia; Dana Foundation; Division of Neuroscience, NIA; Fundación Alzheimur; Genetic Consortium for Late Onset Alzheimer\'s Disease includes a GWAS as part of the Division of Neuroscience, NIA; Gobierno de España; CTS517: Fisiología Molecular
Background: In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population. Methods: We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings. Results: Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genome-wide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls). Conclusions: Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases.
The high-density lipoprotein lipidome in metabolic syndrome: A systematic review
(Wiley, 2026) Grao Cruces, Elena; García‐Jiménez, Gabriel; Martín Rubio, María Esther; Mocciaro, Gabriele; Osto, Elena; Montserrat de la Paz, Sergio; Varela Pérez, Lourdes María; Biología Celular; Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Consejo Superior de Investigaciones Científicas (CSIC)
Background: Metabolic syndrome (MetS) is a cluster of cardiovascular risk fac-tors, including low high-density lipoprotein cholesterol (HDL-C) levels. AlthoughHDL-C is an established cardiovascular biomarker, in MetS this marker capturesonly a fraction of the profound alterations occurring within HDL particles. Thecardiometabolic role of HDLs in MetS remains insufficiently understood be-cause the functional properties and molecular components of HDLs, rather thanHDL-C alone, are likely key determinants of cardiovascular risk. Since the early2000s, research has revealed that HDL particles comprise over 280 proteins andmore than 300 lipid species, underscoring their biological complexity. Moreover,HDL composition and function are extensively remodelled in MetS, highlightingthe importance of characterising the differences in HDL composition betweenhealth and disease. In this systematic review, we aimed to examine differences inthe HDL lipidome between MetS patients and healthy controls.Methods: A comprehensive literature search was conducted in MEDLINE,Cochrane Library, and Web of Science. The PRISMA guidelines for systematicreviews were followed, and four records met the eligibility criteria.Results: Overall, the HDL lipidome was markedly different in MetS comparedwith healthy individuals. MetS was consistently associated with higher levels of triacylglycerides (TAGs) and phosphatidylinositol, alongside lower levels of sev-eral key lipid families, indicating a broad remodelling of HDL composition.Conclusions: These findings indicate that the HDL lipidome is substantiallyaltered in MetS, with potential consequences for HDL functionality. Althoughthe mechanistic implications remain to be fully elucidated, TAG enrichmentmay contribute to lower HDL levels and changes in HDL surface lipids may im-pair essential functions such as cholesterol efflux. Further studies are neededto validate these patterns and determine their impact on HDL function andcardiometabolic risk
Autophagy in obesity and type 2 diabetes: beyond the protective paradigm
(Springer Science and Business Media LLC, 2026-05-08) Angarita-Plánchez, M. Elena; Sánchez-Rodríguez, Paula; Múnera-Rodríguez, Ana M.; Leiva-Castro, Camila; Benítez-Márquez, Juan Manuel; Reina-Pérez, Icíar; Palomares Jerez, María Francisca; López Enríquez, Soledad; Fisiología Médica y Biofísica; Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla/CBUA; Instituto de Salud Carlos III(ISCIII); Unión Europea(programa Ramón y Cajal); Ministerio de Ciencia e Innovación; CTS1100: Inmunometabolismo e Inflamación
Purpose of Review This review examines the current evidence on autophagy dysregulation in obesity and type 2 diabetes mellitus (T2DM), with particular emphasis on its tissue-specific nature and implications for clinical translation. Recent Findings Recent human and preclinical evidence indicates that autophagic alterations in metabolic disease are not uniformly suppressed but vary according to tissue type and disease stage. In adipose tissue, liver, skeletal muscle, pancreatic β cells, and immune cells, dysregulated mTORC1-AMPK signaling, defective mitophagy, and impaired lysosomal function contribute to insulin resistance, ectopic lipid accumulation, and metaflammation. However, most human studies rely on static markers such as LC3, p62, and Beclin-1, which do not reliably reflect dynamic autophagic flux. Recent advances, including organelle-specific biomarkers, ex vivo functional assays, and circulating exosomal cargo, offer new translational opportuni- ties, although standardization remains limited. Summary Autophagy in metabolic disease represents a context-dependent maladaptation rather than a uniformly protectivepathway. Future progress will depend on harmonized biomarker panels, functional assessment of autophagic flux in humans, and integration with metabolic phenotyping to enable precision-based therapeutic strategies.
Low rate of vaccination and risk of incident hepatitis A among HIV-infected men who have sex with men in Seville, Southern Spain
(Elsevier, 2024-05) Fernández-Fuertes, Marta; Macías Sánchez, Juan; Corma-Gómez, Anaïs; Salazar-González, Adolfo; González-Serna Martín, Manuel Alejandro; Rincón, Pilar; Arriaza-Estévez, María J.; Fuentes-López, Ana; Real Navarrete, Luis Miguel; Pineda Vergara, Juan Antonio; Medicina; Fisiología; Bioquímica Médica y Biología Molecular e Inmunología; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Background Periodic outbreaks of hepatitis A (HAV) infection in men who have sex with men (MSM) have been reported. Low vaccination uptake in HIV-infected individuals could drive new outbreaks. We aimed at evaluating the incidence of and risk factors for HAV infection in people living with HIV (PLWH) in our area. We also assessed the rates of HAV vaccination. Methods This was a prospective cohort study. 915 patients were included, 272 (30%) of them were anti-HAV seronegative at baseline. Results Twenty-six (9.6%) susceptible individuals became infected. Incident cases peaked in 2009–2010 and 2017–2018. Incident HAV infection was independently associated with MSM [adjusted odds ratio (95% confidence ratio): 4.39 (1.35–14.27), p = 0.014]. One hundred and five (38.6%) HAV seronegative patients were vaccinated, 21 (20%) of them did not respond, and one (1%) patient lost immunity against HAV. Four (29%) non-responders to vaccination showed incident HAV 5–9 years afterwards. Conclusions The incidence of HAV infection in a cohort of well-controlled PLWH remains low and stable, with intermittent outbreaks involving mainly non-immunized MSM. A significant proportion of PLWH remain susceptible to HAV infection due to insufficient vaccine uptake and limited response to vaccination. Importantly, patients not responding to HAV vaccination continue at risk of infection.
Biomarcadores de laboratorio en la enfermedad de Alzheimer: avances recientes e implantación en un hospital de tercer nivel
(Permanyer, 2025-11-18) Menéndez Valladares, Paloma; Sánchez Fernández, Félix; Olivas-Martínez, Israel; Ortega Ortega, Fernando-Francisco; Pérez-Noguera, Rafael; López-Domínguez, José M.; León Justel, Antonio; Viñuela Fernández, Félix; Bioquímica Médica y Biología Molecular e Inmunología; Medicina
La enfermedad de Alzheimer (EA) es una enfermedad neurodegenerativa crónica que se caracteriza por la acumulación excesiva de proteína beta-amiloide y de proteína Tau fosforilada. Es una enfermedad multifactorial asociada con múltiples factores de riesgo, incluyendo el envejecimiento. Presenta varias etapas: fase preclínica asintomática, deterioro cognitivo leve y demencia. Actualmente se emplean para el diagnóstico biomarcadores en líquido cefalorraquídeo (LCR): proteína amiloide Aβ42, ratio Aβ42/Aβ40, proteína Tau total (t-Tau), y proteína Tau fosforilada (p-Tau181). El diagnóstico se basa en la clasificación biológica de la enfermedad, mediante el sistema AT(N)I: A, depósitos de Aβ-Aβ (PET amiloide, proteínas en LCR [Aβ42 y ratio Aβ42/Aβ40]); T, Tau PET y LCR p-Tau; N, pruebas de imagen y LCR t-Tau, neurofilamentos de cadena ligera (NfL); I, inflamación, proteína ácida fibrilar glial (GFAP). La proteína p-Tau217 en plasma es uno de los biomarcadores emergentes más prometedores en la EA. La variante plasmática de p-Tau es la que mejor concordancia presenta entre plataformas. En la actualidad, la EA no tiene cura. La FDA ha aprobado recientemente dos fármacos, donanemab y lecanemab, que han demostrado su eficacia en la eliminación de la placa Aβ y en la ralentización del deterioro cognitivo, pero no están exentos de efectos secundarios.
In silico prediction and structural characterization of multifunctional bioactive peptides released from olive proteins
(WILEY, 2026-04-08) González de la Rosa, Teresa; Barrera Chamorro, Luna; Fernandez-Prior, Africa; Márquez Parada, Elvira; Torrecillas López, María; Rivero-Pino, Fernando; Montserrat de la Paz, Sergio; Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); CTS1074: Inmunonutrición e Inmunometabolismo
Background: Olive (Olea europaea L.) byproducts, such as seeds and leaves, are abundant agro-industrial residues and represent underexplored protein sources with potential health relevance. However, the repertoire of bioactive peptides that may be released from olive proteins during gastrointestinal digestion remains poorly characterized. This study aimed to perform a comprehensive in silico screening to identify and characterize multifunctional bioactive peptides potentially released from olive proteins during gastrointestinal digestion. Methods: Five UniProt-reviewed Olea europaea L. proteins (annotation score 5/5) were selected as curated reference sequences and subjected to simulated gastrointestinal digestion using pepsin, trypsin, and chymotrypsin. The resulting peptides were filtered and evaluated using a battery of in silico tools to predict physicochemical properties, bioactivity, and bioavailability-related features. Molecular docking analyses were conducted to explore peptide-target interaction patterns. Results: Simulated digestion generated a diverse peptide pool, from which a reduced set of high-ranking candidates was prioritized based on predicted bioactivity. Correlation analyses suggested that structural features such as amphipathicity and steric accessibility were associated with stronger predicted activities. Molecular docking analyses indicated stable and target-specific interaction patterns with proteins involved in cardiometabolic and inflammatory pathways, supporting the prioritization of selected peptide candidates interacting with angiotensin-converting enzyme, dipeptidyl peptidase IV, and the TLR4/MD2 complex. Conclusion: This study provides an integrated in silico screening and prioritization framework to identify olive-derived peptide candidates with predicted multifunctional bioactivity. The findings offer a rational basis to guide future experimental validation and support the valorization of olive byproducts as sources of functional food ingredients. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
El reconocimiento jurídico y social de las prácticas clínicas universitarias: hacia una redefinición de los límites entre formación y trabajo
(Universidad de Sevilla, 2025-12-27) Capitan-Morales, Luis-Cristobal; Capitán Pacheco, Carolina; Calderón Sandubete, Enrique José; López-Campos Bodineau, José Luis; Alba Jiménez, Gonzalo; Cirugía; Medicina; Bioquímica Médica y Biología Molecular e Inmunología; BIO206: BioQuímica de Sistemas Inmunológicos
La aprobación del Real Decreto-ley 2/2023 y su desarrollo mediante la Orden ISM/386/2024 han supuesto un cambio sustancial en el reconocimiento jurídico de las prácticas formativas externas en España, al establecer la obligación generalizada de alta en la Seguridad Social para todo el estudiantado en prácticas, sean o no remuneradas. Esta reforma modifica de manera relevante el estatuto del alumnado y las responsabilidades de universidades y centros sanitarios. El impacto es especialmente significativo en las titulaciones sanitarias, donde las prácticas clínicas constituyen un eje estructural del proceso formativo. En grados como Medicina, Enfermería, Odontología o Fisioterapia, el estudiantado desarrolla una actividad práctica extensa en entornos asistenciales reales, con contacto directo con pacientes, integración en equipos clínicos y participación en procedimientos complejos bajo supervisión. Estas prácticas superan con frecuencia la mera observación, situándose en un espacio intermedio entre formación académica y desempeño clínico tutelado. El nuevo marco normativo reabre el debate sobre la naturaleza jurídica de las prácticas clínicas y sus consecuencias institucionales. Este artículo ofrece una revisión crítica de la evolución legislativa y defiende la necesidad de un marco específico que reconozca su singularidad, garantice la protección social del estudiantado y preserve su esencia académica.
La Tríada Perfecta: enseñar, aprender y divulgar desde la radio universitaria
(Editorial Universidad de Sevilla, 2025-12-27) Lardone, Patricia Judith; Bioquímica Médica y Biología Molecular e Inmunología; CTS160: Neuroinmunoendocrinología Molecular
PSMA-targeted delivery of docetaxel in prostate cancer using small-sized PDA-based micellar nanovectors
(Elsevier, 2025-01-30) Rosales Barrios, Cristian; González Sánchez, Zaira; Zuliani, Alessio; Jiménez Vacas, Juan M.; Luque, Raul M.; Pozo Pérez, David; Khiar, Noureddine; Química Inorgánica; Bioquímica Médica y Biología Molecular e Inmunología; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; Junta de Andalucía; European Union (UE)
In this study, we present the first comparative analysis of active and passive drug delivery systems for docetaxel (DTX) in prostate cancer using supramolecular self-assembled micellar nanovectors. Specifically, we developed two novel micelles based on polydiacetylenic amphiphiles (PDA) for passive and active targeting. The active targeting micelles were designed with a prostate-specific membrane antigen (PSMA) ligand, ACUPA, to facilitate recognition by PSMA-positive cancer cells. These PDA-based micelles feature a well-defined structure with a hydrophobic PDA core and a surface functionalized with PEG, and for active targeting, ACUPA. Our micelles demonstrated excellent encapsulation capacity, significantly improving DTX solubility in water, a crucial factor for clinical drug use. In vitro studies confirmed the safety and cytotoxic profiles of both systems, with ACUPA-functionalized micelles showing notable internalization into PSMA-positive LNCaP cells, mediated through the PSMA-ACUPA interaction. In vivo imaging revealed preferential accumulation of ACUPA-functionalized nanomicelles in LNCaP xenograft tumors, suggesting enhanced retention via specific ACUPA-PSMA interactions and active uptake by LNCaP cells. Notably, Balb/c-Foxn1nu/nu early in vivo studies showed a marked reduction in tumor volume and tumor expression levels of proliferation, cell cycle progression, cell survival and anti-apoptotic markers with DTX-loaded micelles functionalized with ACUPA compared to those without ACUPA. Overall, our studies collect initial evidence regarding the feasibility of supramolecular self-assembly of ACUPA-PDA-based nanomicelles for PSMA-targeted drug chemotherapy delivery developments.
Cell-free DNA levels during the first hours after liver transplantation: a key biomarker for patient survival and outcomes
(MDPI, 2025-11-27) Macher, Hada C.; Rubio-Prieto, José L; García-Fernández, Noelia; Molinero Hueso, Patrocinio; Gómez Bravo, Miguel Ángel; Guerrero Montávez, Juan Miguel; Suárez Artacho, Gonzalo; Rubio Calvo, Amalia Macarena; Cirugía; Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Consejera de Salud de la Junta de Andaluca; CTS664: Cirugía Avanzada y Trasplantes. Terapia Celular y Bioingeniería Aplicada a la Cirugía; CTS160: Neuroinmunoendocrinología Molecular
Background: We propose that cfDNA levels may serve as a valuable biomarker for monitoring the progress of liver transplant recipients, reflecting the quality of the donated organ, and predicting patient prognosis and survival. Thus, we analyzed the relationship between total cfDNA levels during the first 48 h post-transplantation, ischemia-reperfusion injury, and patient outcomes. Methods: cfDNA quantification was applied to 115 liver transplant patients using real-time quantitative PCR at the time of transplantation (during reperfusion) and throughout the first month post-transplantation. Results: Significantly higher early cfDNA levels were observed in patients who suffered liver damage or post-transplantation complications during the first month. High cfDNA levels were also associated with prolonged ICU stays and reduced survival. Kaplan-Meier analysis revealed a significantly lower survival rate in patients with elevated cfDNA. CRP levels were elevated and significantly correlated with cfDNA values. Regarding organ preservation prior to transplantation, prolonged cold and warm ischemia times were significantly associated with high cfDNA levels in the early hours post-transplantation. Conclusions: Elevated cfDNA levels in the early hours following liver transplantation are associated with poorer patient outcomes. Therefore, determining total cfDNA levels post-transplantation may be a valuable tool for patient management and early intervention.
Resin-modified calcium silicate-based materials versus conventional formulations in primary teeth: a systematic review and meta-analysis of clinical and radiographic outcomes of vital pulp therapy procedures in pediatric dentistry
(MDPI, 2026-03-17) Cabrera Fernández, Alberto; Dominguez-Dominguez, Laura; Pérez Pérez, Antonio; Santos, João Miguel Marques dos; Díaz-Cuenca, Aránzazu; Sánchez Margalet, Víctor; Sequeira, Diana B.; Segura Egea, Juan José; Martín González, Jenifer; Estomatología; Bioquímica Médica y Biología Molecular e Inmunología; CTS941: Patología Dentaria, Operatoria Dental y Endodoncia; CTS151: Bioquímica Medica
Vital pulp therapy comprises a group of procedures whose use in the primary dentition is increasingly supported in pediatric dentistry. The clinical management of pediatric patients requires biomaterials that provide precision, ease of handling, and reduced chairside time; in this context, resin-modified calcium silicate-based materials (RM-CSCs) have been introduced as an alternative to conventional calcium silicate formulations. This systematic review and meta-analysis aimed to evaluate the clinical effectiveness of RM-CSCs compared with non-resin calcium silicate-based materials in vital pulp therapy performed in primary teeth. A systematic search was conducted in MEDLINE, Scopus, Embase, and Web of Science in accordance with PRISMA guidelines. Randomized clinical trials were included, the risk of bias was assessed using the RoB 2 tool, and the certainty of evidence was evaluated using the GRADE approach. Of the 605 records initially identified, nine randomized clinical trials were ultimately included, all of which evaluated TheraCal LC as the RM-CSC. Meta-analyses were performed for vital pulp therapy overall and for procedure-specific subanalyses, including indirect pulp capping and pulpotomy. None of the meta-analyses demonstrated statistically significant differences between RM-CSCs and non-resin calcium silicate-based materials in terms of clinical or radiographic success. Therefore, the available evidence supports the use of TheraCal LC as an effective option for indirect pulp capping in primary teeth; however, its use in pulpotomy should be interpreted with caution until further randomized clinical trials become available.
Fatty acid composition of isoenergetic meals drives distinct postprandial immunometabolic responses in healthy adults: A randomized crossover pilot study
(Elsevier, 2026-04) Márquez Parada, Elvira; Torrecillas López, María; Corell Almuraza, Alfredo; González de la Rosa, Teresa; Barrera Chamorro, Luna; Bermúdez Pulgarín, Beatriz; Claro Cala, Carmen María; Montserrat de la Paz, Sergio; Bioquímica Médica y Biología Molecular e Inmunología; Biología Celular; Farmacología, Pediatría y Radiología; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
The postprandial period represents a critical and dynamic phase during which dietary components can acutely influence metabolic and immune functions. While the chronic effects of dietary fat quality are well characterized, their immediate postprandial immunometabolic impact remains poorly understood. To investigate the acute effects of energy-matched test meals enriched in saturated (SFA), monounsaturated (MUFA), or omega-3 long-chain polyunsaturated fatty acids (ω3-LCPUFA), compared to a fat-free control, on systemic metabolic and immune parameters in healthy adults. In this randomized, crossover pilot study, ten healthy participants consumed four test meals separated by 2-week washouts. Blood samples were collected at fasting, 2–3 h (peak), and 5–6 h (late phase) postprandially. Biochemical and immunological biomarkers were assessed. Statistical analyses included two-way repeated-measures ANOVA, linear mixed models, and area under the curve (AUC/iAUC) calculations. MUFA- and ω3-LCPUFA-enriched meals induced significantly greater postprandial changes in glucose, triacylglycerides, LDL-C, and C-peptide compared to the SFA and fat-free meals, particularly at the late postprandial phase. These effects were confirmed by AUC and iAUC analyses. In contrast, although transient changes in immune cell counts and humoral markers were observed over time, no significant differences between fat types were detected in postprandial immune responses. In healthy adults, the fatty acid composition of energy-matched meals acutely modulates key metabolic pathways in a fat-type-specific manner, whereas systemic immune parameters remain largely unchanged. These preliminary findings suggest a functional dissociation between postprandial metabolic and immune response and underscore the need to more sensitive or compartment-specific immune readouts in future nutritional research.
Niveles séricos de vitaminas en pacientes críticos y su relación con el pronóstico
(Aula medica ediciones; Aran ediciones, S L, 2025-10-31) Garnacho Montero, José; María Ascensión González-García; Fernández Castillo, Rafael Jesús; González-Caro, M.D.; Gutiérrez‐Pizarraya, Antonio; Arrobas Velilla, Teresa; Sánchez Margalet, Víctor; Enfermería; Bioquímica Médica y Biología Molecular e Inmunología; CTS1141: Investigación Clínica Aplicada a los Cuidados y Nuevos Paradigmas Asistenciales; CTS151: Bioquímica Medica
Objetivos: conocer los niveles séricos de vitaminas (A, D, E, K, B1, B6 y B12) en pacientes críticos, sus cambios y su impacto en la mortalidad en la unidad de cuidados intensivos. Métodos: estudio prospectivo. Se midieron los niveles séricos de vitaminas A, D, E, K, B1, B6 y B12 basalmente, en día 7 y día 14, así como las diferencias en los mismos según si el paciente recibía o no NP con un complejo multivitamínico que no contiene vitamina K. Se realizó análisis multivariante para estudiar factores relacionados con mortalidad. Resultados: se analizaron 99 pacientes. La edad mediana fue 59 años y el 35,4 % (n = 35) mujeres. Los niveles de vitamina A, K y D estaban bajos al ingreso; aumentaron en los días 7 y 14 alcanzando valores normales en el primer caso, no así para la K y D. Los valores de las vitaminas B1 y E se encuentran dentro de la normalidad y elevados los niveles de las vitaminas B6 y B12. Valores más altos de NUTRIC score (OR: 1,38, IC 95 %: 1,07-1,77) y de vitamina E al ingreso se relacionaron independientemente con un peor y mejor pronóstico, respectivamente. En los pacientes con NP los niveles de vitamina A y E suben significativamente a los 7 y 14 días respecto al basal sin cambios significativos en el resto de las vitaminas estudiadas. Conclusiones: en este grupo heterogéneo de pacientes críticos, los niveles de las vitaminas A, D y K se encuentran disminuidos, normales los de las vitaminas B1 y E y elevados los de las vitaminas B6 y B12. La nutrición parenteral con suplementación vitamínica, pero sin vitamina K, mantiene adecuados niveles séricos de la vitamina K. Solo hemos identificado como factor asociado al pronóstico que el nivel basal de vitamina E es factor protector de mortalidad.
High leptin levels independent of body mass index are associated with inflammation and poorer treatment response in patients with diffuse large B-cell lymphoma
(Elsevier, 2026-02) Hontecillas-Prieto, Lourdes; García-Domínguez, Daniel J.; Jiménez Cortegana, Carlos; Nogales-Fernández, Esteban; Palazón-Carrión, Natalia; García Sancho, Alejandro Martín; Ríos Herranz, Eduardo; Cruz Merino, Luis de la; Sánchez Margalet, Víctor; Instituto de Biomedicina de Sevilla (IBIS); Medicina; Instituto de Biomedicina de Sevilla (IBIS); Clinical Trial Unit, Hospital Universitario Virgen del Rocío, Spanish Clinical Research and Clinical Trial Platform (CTU-HUVR); Biobank Nodo Hospital Virgen Macarena (Biobanco del Sistema Sanitario Público de Andalucía); Spanish National biobanks Networ; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); CTS151: Bioquímica Medica
Leptin, a protein hormone secreted mainly by adipocytes, plays a key role in modulating various physiological processes. Dysregulation of this hormone has been linked to numerous diseases, including the immunological system and cancer. In patients with diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma (NHL), elevated levels of leptin appear to contribute to the development and progression of lymphoma by modulating the immune system and creating a proinflammatory environment, where lymphoma patients have a lower survival rate compared to those with normal levels. It therefore appears that leptin plays a role in inflammation, the immune system and the development of lymphoma. However, there is a need to fully understand the mechanisms involved and to develop targeted therapies for lymphoma. Our results show that leptin levels are increased (independently of body mass index) in patients with DLBCL belonging to the R2-GDP-GOTEL phase II clinical trial, and these elevated levels are associated with a worse response to treatment and survival using lenalidomide as immunomodulator. Furthermore, a positive correlation between leptin and the inflammation marker C-reactive protein (CRP) is observed, and a multivariate analysis reveals a correlation between leptin, CRP and Monocytic Myeloid-derived suppressor cells (M-MDSC) levels in patients with worse response to treatment. Taken together, these data indicate that leptin could be a promising and predictive response biomarker of treatment efficacy in patients with lymphoma. Our findings on leptin in patients with R/R DLBCL could also arouse great interest given its potential applications as a target of treatment.
Integratomic investigation to assess the liver lipidomic and antiinflammatory activity of lupin protein hydrolysate
(Nature Research, 2025-07-28) Casati, Sara; Dei Cas, Michele; d'Adduzio, Lorenza; Cruz Chamorro, Iván; Santos Sánchez, Guillermo; Bollati, Carlotta; Fanzaga, Melissa; Pedroche, Justo; Millán Linares, María del Carmen; Roda, Gabriella; Carrillo Vico, Antonio; Lammi, Carmen; Bioquímica Médica y Biología Molecular e Inmunología; Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España; Ministero dell’Università e della Ricerca (Italia); Università degli Studi di Milano; European Union (UE); CTS160: Neuroinmunoendocrinología Molecular
Chronic inflammation plays a significant role in the development and progression of metabolic dysfunction-related diseases. This study investigating a protein hydrolysate from Lupinus angustifolius (LPH) in mice model on a western diet (WD) aimed to elucidate its potential beneficial role in improving the lipidomic and anti-inflammatory profile. To achieve this objective, a lipidomic approach in combination with the evaluation of protein level modulation of selected key enzymes that are pivotal involved in the bioactive lipid pathway synthesis/regulation was performed on liver homogenates. Specifically, LPH positively impacted DHCer, SM, LacCer, Sph 1, DHSph 1, and S1P 1 concentrations, and restored the basal conditions of ASAH1 and ASM, proteins involved in sphingolipid metabolism. LPH also reduced the FASN and PPARγ levels and eicosanoids, with positive modulation of the COX-2 and ALOX5. Additionally, LPH reduced the WB-induced AEA and 2AG concentrations.
Melatonin controls experimental autoimmune encephalomyelitis by altering the T effector/regulatory balance
(Elsevier, 2015-06-26) Álvarez Sánchez, Nuria; Cruz Chamorro, Iván; López González, Antonio; Utrilla Alcolea, José Carmelo; Fernández-Santos, José María; Martínez López, Alicia; Lardone, Patricia Judith; Guerrero Montávez, Juan Miguel; Carrillo Vico, Antonio; Bioquímica Médica y Biología Molecular e Inmunología; Citología e Histología Normal y Patológica; Bioquímica y Biología Molecular; Instituto de Salud Carlos III; Gobierno de España; Junta de Andalucía; CTS439: Sistema Neuroendocrino Difuso; CTS160: NeuroInmunoEndocrinología Molecular
Experimental autoimmune encephalomyelitis (EAE), the experimental model for multiple sclerosis (MS), is triggered by myelin-specific Th1 and Th17 cells. The immunomodulatory activities of melatonin have been shown to be beneficial under several conditions in which the immune system is exacerbated. Here, we sought to elucidate the basis of the melatonin protective effect on EAE by characterizing the T effector/regulatory responses, particularly those of the memory cell subsets. Melatonin was tested for its effect on Th1, Th17 and T regulatory (Treg) cells in the lymph nodes and CNS of immunodominant peptide of myelin oligodendrocyte glycoprotein (pMOG)-immunized and EAE mice, respectively. The capacity of melatonin to ameliorate EAE as well as modifying both T cell response and effector/regulatory balance was surveyed. T cell memory subsets and CD44, a key activation marker involved in the EAE pathogenesis, were also examined. Melatonin protected from EAE by decreasing peripheral and central Th1/Th17 responses and enhancing both the Treg frequency and IL-10 synthesis in the CNS. Melatonin reduced the T effector memory population and its pro-inflammatory response and regulated CD44 expression, which was decreased in T effector cells and increased in Tregs. The alterations in the T cell subpopulations were associated with a reduced mononuclear infiltration (CD4 and CD11b cells) of the melatonin-treated mice CNS. For the first time, we report that melatonin protects against EAE by controlling peripheral and central T effector/regulatory responses, effects that might be partially mediated by CD44. This immunomodulatory effect on EAE suggests that melatonin may represent an effective treatment option for MS.
Melatonin reduces inflammatory response in peripheral T helper lymphocytes from relapsing-remitting multiple sclerosis patients
(WILEY, 2017-08-09) Álvarez-Sánchez, Nuria; Cruz Chamorro, Ivan; Díaz-Sánchez, María; Sarmiento-Soto, Helia; Medrano-Campillo, Pablo; Martínez-López, Alicia; Lardone, Patricia Judith; Guerrero Montávez, Juan Miguel; Carrillo Vico, Antonio; Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); CTS160: Neuroinmunoendocrinología Molecular
Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system in which the immune system plays a central role. In particular, effector populations such as T helper (Th) 1, Th9, Th17, and Th22 cells are involved in disease development, whereas T regulatory cells (Tregs) are associated with the resolution of the disease. Melatonin levels are impaired in patients with MS, and exogenous melatonin ameliorates the disease in MS animal models by modulating the Th1/Th17/Treg responses and also improves quality of life and several symptoms in patients with MS. However, no study has examined melatonin's effect on T cells from relapsing-remitting MS (RR-MS) patients. Therefore, the objectives of the present study were to evaluate the effects of the in vitro administration of melatonin to peripheral blood mononuclear cells (PBMCs) from 64 RR-MS patients and 64 sex- and age-matched healthy subjects on Th1, Th9, Th17, Th22, and Treg responses and to analyze the expression of the melatonin effector/receptor system in these cells. Melatonin decreased Th1 and Th22 responses in patients, whereas it did not affect the Th17 and Treg subsets. Melatonin also promoted skewing toward a more protective cytokine microenvironment, as shown by an increased anti-inflammatory/Th1 ratio. Furthermore, for the first time, we describe the overexpression of the melatonin effector/receptor system in PBMCs from patients with MS; this alteration might be relevant to the disease because acetylserotonin O-methyltransferase expression significantly correlates with disease progression and T effector/regulatory responses in patients. Therefore, our data suggest that melatonin may be an effective treatment for MS.
Challenges in accurate HDV RNA quantification: inter-assay variability and the impact of thermal shock
(Amer soc microbiology, 2025-12-31) Pérez-García, F; Virseda-Berdices, A; Pita-Martínez, C; Monte, MM; Sepúlveda-Crespo, D; Macías Sánchez, Juan; Real Navarrete, Luis Miguel; Resino, Sergio; Bioquímica Médica y Biología Molecular e Inmunología; Medicina; Instituto de Biomedicina de Sevilla (IBIS); Centro de Investigacin en Red en Enfermedades Infecciosas; Sociedad Europea de Microbiología Clínica y Enfermedades Infecciosas; Fundación para la Investigación Biomédica del Hospital Universitario Príncipe de Asturias; Instituto de Salud Carlos III
Quantitative RT-PCR (qRT-PCR) is essential for monitoring hepatitis delta virus (HDV) RNA, yet assays lack standardization. We aimed to evaluate the performance of three qRT-PCR assays and to assess the impact of a pre-analytical thermal shock procedure. We conducted a comparative study using 206 samples (106 with anti-HDV antibodies and 100 anti-HDV-negative as a control group), which were tested in parallel with three qRT-PCR assays: Vircell, Certest, and Altona. Performance was evaluated for inter-assay agreement (kappa index), quantitative correlation (R²), and bias (Bland-Altman). Altona detected 56 HDV-RNA positive samples, whereas Vircell and Certest detected 55 positive samples. Inter-assay agreement was perfect comparing Vircell vs Certest (agreement = 100%, к = 1.000) and almost perfect comparing Altona with both Vircell and Certest (agreement = 99.5%, к = 0.988). Quantitatively, Vircell and Certest assays showed relevant systematic biases compared to Altona, overestimating viral loads by approximately 0.24 log10 International Units (IU)/mL (Certest) and 0.33 log10 IU/mL (Vircell). The correlation with Altona was strong for Certest (R² = 0.864) and moderate for Vircell (R² = 0.793), while the correlation between Certest and Vircell was weaker (R² = 0.720). Thermal shock improved sensitivity in one case (Certest vs Vircell) but increased quantitative variability, worsening the inter-assay correlation (R² = 0.684). In conclusion, all three assays were highly concordant for the qualitative diagnosis of HDV infection, but their quantitative biases prevent their interchangeable use for treatment monitoring. Thermal shock is not recommended for routine monitoring, as a significant compromise in quantitative accuracy and precision outweighs any potential gains in sensitivity.IMPORTANCEThis study evaluates three hepatitis delta virus (HDV) RNA quantitative real-time PCR (qRT-PCR) assays, crucial for managing the HDV infection, particularly in the setting of new therapies like Bulevirtide, where assessing viral load reduction and accurate monitoring is paramount. We reveal significant quantitative biases among widely used assays, precluding their interchangeable use and risking misinterpretation of treatment response. Furthermore, our systematic assessment of the thermal shock pre-analytical procedure highlights its detrimental impact on quantitative precision, despite modest sensitivity gains. This work provides essential evidence for clinicians and laboratories, guiding assay selection and standardization efforts to optimize HDV diagnosis and patient monitoring.
First genome-wide association study reveals immune-mediated aetiopathology in idiopathic achalasia
(BMJ Publishing group, 2026) Grover, S; Gockel, I; Latiano, Anna; Mokrowiecka, Anna; Dasmeh, P; Wouters, MM; Real Navarrete, Luis Miguel; Schumacher, J; Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Asociación de Alzheimer; Programa Conjunto de la UE - Investigación sobre Enfermedades Neurodegenerativas; Fondo Social Europeo; Programa LABEX DISTALZ del gobierno francés (desarrollo de estrategias innovadoras para un enfoque transdisciplinario); Sociedad Francesa de Gastroenterología (SNFGE, Société Nationale Francaise de GastroEnterologie); Fundación Alemana de Investigación (DFG); INSERM; Instituto Pasteur de Lille, Lille Métropole Communaute Urbaine; Ministerio de Salud y Solidaridad Social (Grecia); Marco Estratégico Nacional de Referencia-programa de la UE
Background: Idiopathic achalasia (IA) is characterised by the degeneration of neurons in the myenteric plexus leading to an irreversible impaired oesophageal function. Although immune-mediated mechanisms have been proposed, the underlying aetiopathology of IA remains poorly understood. Objective: This study aimed to uncover the genetic risk architecture of IA. Design: We carried out the first genome-wide association study (GWAS) on 4602 European patients with IA and 10 766 ethnically-matched controls. Results: A single nucleotide polymorphism (SNP) in HLA-DQB1 leading to an 8-amino acid insertion on the protein level conferred strongest IA risk (PQGPPPAG: p=3.27×10-68, OR=2.45). Conditional analyses within the HLA locus revealed a complex genetic risk architecture. Three additional amino acid positions showed independent IA association (Omnibus p<5×10-8). These refer to positions 41 and 130 in HLA-DQα1, position 45 in HLA-DQβ1 and position 86 in HLA-DRβ1. Together, these findings highlight the pivotal role of class II HLA genetic variation in IA pathogenesis. Outside HLA, three independent variants showed IA association (p<5×10-8). One leads to an amino acid substitution with functional effect in PTPN22. Another risk variant leads to a downregulated expression of TNFSF8, TNFSF15 and TNC in immune cells. The third risk SNP is located near ZNF365, but the exact underlying cellular mechanism remains unknown. Beyond the single marker level, polygenic risk scores revealed that patients with IA can be stratified based on their genetic risk. In addition, IA shows a shared aetiopathology with Crohn's disease (rg=0.335). Integrating GWAS and single-cell RNA-sequencing data from the myenteric plexus showed that the memory T-cell type FOS+Tc4+CD8+ plays a central role in IA development (p=2.50×10-19). Conclusion: This GWAS led to the identification of SNPs, cellular mechanisms and cell types that are involved in IA aetiopathology.

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