Artículos (Bioquímica Médica y Biología Molecular e Inmunología)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/10990

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Prospective, randomized, double-blind parallel group nutritional study to evaluate the effects of routine intake of fresh vs. Pasteurized yogurt on the immune system in healthy adults
(Mdpi, 2024-06-20) Rivero-Pino, Fernando; Casquete, Mar; Castro, Maria Jose; Redondo del Rio, Paz; Gutierrez, Eloina; Mayo-Iscar, Agustin; Nocito, Mercedes; Corell-Almuzara, Alfredo; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. CTS 1074: InmunoNutrición e InmunoMetabolismo.
The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit healthy populations by delaying or preventing the emergence of immune-mediated chronic illnesses. In this study, the purpose was to describe and compare the modulator effects on the immune system of the routine ingestion of fresh vs. pasteurized yogurt. A unicentral, prospective, randomized, double-blind, parallel group 8-week nutritional study was carried out comparing the ingestion of 125 g of the products in healthy adults three times a day. A complete battery of in vitro tests on the activity of the immune system, processes and phenomena was performed. Exclusive immune-modulatory effects of fresh yogurt with respect to base line werefoundintermsofincreasedsystemicIgM(primaryimmune responses), increased synthesis of IFN-gamma uponstimulation (Th1) andincreasedperipheral Tcells (mainly “naive” CD4s). In the three interventions, we observed an increased phagocytic activity and burst test in granulocytes, together with increased secretion of IL-6, IL-1 β and IL-8 (pro-inflammatory) and increased CD16 expression (FcR favoring phagocytosis) in granulocytes. Overall, it is concluded that regardless of bacteria being alive or thermally inactivated, yogurt has common effects on the innate system, but the presence of live bacteria is necessary to achieve a potentiating effect on the specific immune response.
Mediterranean diet combined with regular aerobic exercise and hempprotein supplementation modulates plasma circulating amino acids and improves the health status of overweight individuals
(Mdpi, 2024-05-23) Miguel Albarreal, Antonio de; Rivero-Pino, Fernando; Márquez Parada, Elvira; Grao Cruces, Elena; González de la Rosa, Teresa; Montserrat de la Paz, Sergio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Junta de Andalucía; Gobierno de España; Universidad de Sevilla. CTS 1074: InmunoNutrición e InmunoMetabolismo.
Plant protein is considered a sustainable health-promoting strategy to prevent metabolic syndrome. Lifestyle changes (including dietary patterns and exercise) have been demonstrated to exert an effect on human health by modulating the biochemical status in humans. The objective of this study was to assess whether supplementation with hemp protein within a Mediterranean diet context together with exercise could help to ameliorate the metabolic statuses of patients prone to developing metabolic syndrome. For this study, 23 patients followed with Mediterranean diet and engaged in aerobic exercise according to the WHO’s recommendations, while also being supplemented with hemp protein, for 12 weeks. A comparison of anthropometric, biochemical, and mineral data as well as amino acid values was made between the start and the end of the study, with the subjects acting as their own control group. Statistical analyses included a paired t-test, Wilcoxon paired test, Pearson correlation coefficient, and Sparse Partial Least Squares Discriminant Analysis to evaluate significant differences and correlations among parameters. There were statistically significant changes in total cholesterol, HDL-C (+52.3%), LDL-C (−54.0%), and TAG levels (−49.8%), but not in glucose plasma levels. Following the intervention, plasma concentrations of some amino acids, including α-aminoadipic acid, phosphoethanolamine, and 1-metylhistidine, increased, whereas those of asparagine and alanine declined. Different correlations between amino acids and the other parameters evaluated were reported and discussed. A Mediterranean diet combined with regular aerobic exercise, together with protein supplementation, can highly improve the metabolic parameters and anthropometric parameters of subjects with obesity and impaired glucose levels, ameliorating their health status and likely delaying the development of metabolic syndrome
Vedolizumab and ART in recent HIV-1 infection unveil the role of α4β7 in reservoir size
(American Society for Clinical Investigation, 2024-08-22) Jimenez-Leon, Maria Reyes; Gasca-Capote, Carmen; Roca-Oporto, Cristina; Espinosa, Nuria; Sobrino, Salvador; Fontillon-Alberdi, Maria; Cervera Barajas, Antonio; Bachiller, Sara; López Cortés, Luis Fernando; Ruiz-Mateos, Ezequiel; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. Departamento de Medicina; Bioquímica Médica y Biología Molecular e Inmunología; Conocimiento, Empresas y Universidad; Conserjeria de Economia; Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, "a way to make Europe,"; Junta de Andalucia; Red Tematica de Investigacion Cooperativa en SIDA; Spanish National Research Council
BACKGROUNDWe evaluated the safety and viral rebound, after analytical treatment interruption (ATI), of vedolizumab and ART in recent HIV-1 infection. We used this model to analyze the effect of α4β7 on the HIV-1 reservoir size.METHODSParticipants started ART with monthly vedolizumab infusions, and ATI was performed at week 24. Biopsies were obtained from ileum and cecum at baseline and week 24. Vedolizumab levels, HIV-1 reservoir, flow cytometry, and cell-sorting and antibody competition experiments were assayed.RESULTSVedolizumab was safe and well tolerated. No participant achieved undetectable viremia off ART 24 weeks after ATI. Only a modest effect on the time to achieve more than 1,000 HIV-1 RNA copies/mL and the proportion of participants off ART was observed, being higher in the vedolizumab group compared with historical controls. Just before ATI, α4β7 expression was associated with HIV-1 DNA and RNA in peripheral blood and with PD1 and TIGIT levels. Importantly, a complete blocking of α4β7 was observed on peripheral CD4+ T cells but not in gut (ileum and cecum), where α4β7 blockade and vedolizumab levels were inversely associated with HIV-1 DNA.CONCLUSIONOur findings support α4β7 as an important determinant in HIV-1 reservoir size, suggesting the complete α4β7 blockade in tissue as a promising tool for HIV-cure combination strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT03577782.FUNDINGThis work was supported by the Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, "a way to make Europe," research contracts FI17/00186 and FI19/00083 and research projects PI18/01532, PI19/01127, PI22/01796), Conserjería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (research projects P20/00906), the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020), and the Spanish National Research Council.
A second update on mapping the human genetic architecture of COVID-19
(Nature Research, 2023-09-06) Romero Gómez, Manuel; Horra Padilla, Carmen de la; Calderón Sandubete, Enrique José; Medrano Ortega, Francisco Javier; Ampuero Herrojo, Javier; Delgado de la Cuesta, Juan; Guerrero Montávez, Juan Miguel; Morilla Romero de la Osa, Rubén; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. Departamento de Medicina; NIA NIH HHS
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)
Melatonin synergistically potentiates the effect of methylprednisolone on reducing neuroinflammation in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis
(Elsevier, 2024) Álvarez López, Ana Isabel; Álvarez-Sánchez, Nuria; Cruz Chamorro, Iván; Santos-Sánchez, Guillermo; Ponce España, Eduardo; Bejarano, Ignacio; Lardone, Patricia Judith; Carrillo Vico, Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Andalusian Government Ministry of Health; PAIDI Program from the Andalusian Government; Progress and Health Foundation; Regional Ministry of Economy and Knowledge of Andalusia; Spanish Ministerio de Educacion, Cultura y Deporte; VI Program of Inner Initiative for Research and Transfer of the University of Seville [VI PPIT-US]
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 of relapses in MS.
Anti-obesogenic effect of lupin-derived protein hydrolysate through modulation of adiposopathy, insulin resistance and gut dysbiosis in a diet-induced obese mouse
(Elsevier, 2024) Ponce España, Eduardo; Cruz Chamorro, Iván; Santos Sánchez, Guillermo; Alvarez-Lopez, Ana Isabel; Fernández-Santos, José María; Pedroche, Justo; Millán-Linares, MC; Bejarano Hernando, Ignacio; Lardone, Patricia Judith; Carrillo Vico, Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica
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.
Immunoregulatory properties of melatonin in the humoral immune system: a narrative review
(Elsevier, 2024-07-18) Calvo Gutiérrez, Juan Ramón; Maldonado y Aibar, María Dolores; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. CTS 160: Neuroinmunoendocrinologia molecular
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.
The Expression of Genes Related to Reverse Cholesterol Transport and Leptin Receptor Pathways in Peripheral Blood Mononuclear Cells Are Decreased in Morbid Obesity and Related to Liver Function
(MDPI, 2024) Jiménez-Cortegana, Carlos; López Enriquez, Soledad; Alba Jiménez, Gonzalo; Santa-María Pérez, Consuelo; Martín-Núñez, Gracia M.; Moreno-Ruiz, Francisco J.; Valdés, Sergio; García-Serrano, Sara; Sánchez Margalet, Víctor; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
Obesity is frequently accompanied by non-alcoholic fatty liver disease (NAFLD). These two diseases are associated with altered lipid metabolism, in which reverse cholesterol transport (LXRα/ABCA1/ABCG1) and leptin response (leptin receptor (Ob-Rb)/Sam68) are involved. The two pathways were evaluated in peripheral blood mononuclear cells (PBMCs) from 86 patients with morbid obesity (MO) before and six months after Roux-en-Y gastric bypass (RYGB) and 38 non-obese subjects. In the LXRα pathway, LXRα, ABCA1, and ABCG1 mRNA expressions were decreased in MO compared to non-obese subjects (p < 0.001, respectively). Ob-Rb was decreased (p < 0.001), whereas Sam68 was increased (p < 0.001) in MO. RYGB did not change mRNA gene expressions. In the MO group, the LXRα pathway (LXRα/ABCA1/ABCG1) negatively correlated with obesity-related variables (weight, body mass index, and hip), inflammation (C-reactive protein), and liver function (alanine-aminotransferase, alkaline phosphatase, and fatty liver index), and positively with serum albumin. In the Ob-R pathway, Ob-Rb and Sam68 negatively correlated with alanine-aminotransferase and positively with albumin. The alteration of LXRα and Ob-R pathways may play an important role in NAFLD development in MO. It is possible that MO patients may require more than 6 months following RYBGB to normalize gene expression related to reverse cholesterol transport or leptin responsiveness.
Editorial: Immunometabolism: bridging the gap between immunology and nutrition
(Frontiers Media S.A., 2024-06-12) Basso, P.J.; Gauthier, T.; Palomares, Francisca; López Enriquez, Soledad; Tsai, S.; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
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.
Sulforaphane-mediated immune regulation through inhibition of NF-kB and MAPK signaling pathways in human dendritic cells
(Elsevier, 2024-06) Múnera-Rodríguez, Ana M.; Leiva-Castro, Camila; Sobrino, Francisco; López Enriquez, Soledad; Palomares, Francisca; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
Inflammation and immune responses are intricately intertwined processes crucial for maintaining homeostasis and combating against pathogens. These processes involve complex signaling pathways, notably the Nuclear Factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) pathways, which play crucial roles. Sulforaphane (SFN), a nutraceutic, has emerged as a potential regulator of NF-κB and MAPK signaling pathways, exhibiting anti-inflammatory properties. However, limited knowledge exists regarding SFN’s effects on immune cell modulation. This study aimed to assess the immunomodulatory capacity of SFN pretreatment in human dendritic cells (DCs), followed by exposure to a chronic inflammatory environment induced by lipopolysaccharide. SFN pretreatment was found to inhibit the NF-κB and MAPK signaling pathways, resulting in phenotypic changes in DCs characterized by a slight reduction in the expression of surface markers, as well as a decrease of TNF-α/IL-10 ratio. Additionally, SFN pretreatment enhanced the proliferation of Treg-cells and promoted the production of IL-10 by B-cells before exposure to the chronic inflammatory environment. Furthermore, these changes in DCs were found to be influenced by the inhibition of NF-κB and MAPK pathways (specifically p38 MAPK and JNK), suggesting that these pathways may play a role in the regulation of the differentiation of adaptive immune responses (proliferation of T- and IL-10-producing regulatory-cells), prior to SFN pretreatment. Our findings suggest that SFN pretreatment may induce a regulatory response by inhibiting NF-κB and MAPK signaling pathways in an inflammatory environment. SFN could be considered a promising strategy for utilizing functional foods to protect against inflammation and develop immunoregulatory interventions.
Influence of Natural Crosslinkers on Chitosan Hydrogels for Potential Biomedical Applications
(Wiley, 2023-09) Sánchez Cid, Pablo; Gónzalez-Ulloa, Gabriel; Alonso González, María; Jiménez-Rosado, Mercedes; Rafii-El-Idrissi Benhnia, Mohammed; Romero García, Alberto; Ostos Marcos, Francisco José; Pérez-Puyana, Víctor Manuel; Universidad de Sevilla. Departamento de Ingeniería Química; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; European Commission. Fondo Social Europeo (FSO); Universidad de Sevilla. TEP229: Tecnología y Diseño de Productos Multicomponentes; Universidad de Sevilla. CTS590: Inmunovirología (Sistema Sanitario Público de Andalucía. Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI)); Universidad de Sevilla. FQM206: Grupo de Cinética del Profesor Rodríguez Velasco
Chitosan (CH) is a very well-known biopolymer that has been widely used for the development of biomaterials with a wide range of applications in the biomedical field, such as the preparation of hydrogels, owing to its outstanding anti-inflammatory, antibacterial and antifungal properties, biocompatibility and biodegradability, although they present limited mechanical properties. Chemical crosslinking is one of the most recurrent strategies for the reinforcement of these structures and, above all, crosslinking with natural-origin compounds that do not compromise their biocompatibility is considered a hot topic in this research field. D-fructose (F), obtained from the hydrolyzation and further isomerization of starch, an abundant raw material and genipin (G), which is extracted from the fruits of Gardenia jasminoides Ellis are used as natural crosslinkers. Chitosan-based hydrogels crosslinked with each crosslinking agent are prepared and characterized through Fourier transform infrared (FTIR) spectroscopy, crosslinking and swelling degree determination, rheological, microstructural, and biological studies. The results demonstrate that crosslinking with G is more beneficial for chitosan-based hydrogels since these samples showed more compact structures and better rheological performance. Additionally, excellent biological in vitro behavior due to the crosslinking with G, unlike that of F.
The absence of seroconversion after exposition to hepatitis C virus is not related to KIR-HLA genotype combinations (GEHEP-012 study)
(Elsevier, 2024) Martín Sierra, Carmen; José Bravo, María; Sáez, María E.; de Rojas, Itziar; Santos, Marta; Martín Carmona, Jesica; González-Serna Martín, Manuel Alejandro; Pineda Vergara, Juan Antonio; Macías Sánchez, Juan; Real Navarrete, Luis Miguel; Universidad de Sevilla. Departamento de Fisiología; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Medicina; Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica; Junta de Andalucía; CIBERINFEC; Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE)
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.
Hybrid polymeric Hydrogel-based biomaterials with potential applications in regenerative medicine
(Elsevier, 2023-08) González-Ulloa, Gabriel; Jiménez-Rosado, Mercedes; Rafii-El-Idrissi Benhnia, Mohammed; Romero García, Alberto; Ruiz-Mateos Carmona, Ezequiel; Ostos Marcos, Francisco José; Pérez-Puyana, Víctor Manuel; Universidad de Sevilla. Departamento de Ingeniería Química; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; European Commission. Fondo Social Europeo (FSO); Universidad de Sevilla. TEP229: Tecnología y Diseño de Productos Multicomponentes; Universidad de Sevilla. CTS590: Inmunovirología (Sistema Sanitario Público de Andalucía. Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI)); Universidad de Sevilla. FQM206: Grupo de Cinética del Profesor Rodríguez Velasco
In the field of regenerative medicine, the use of biomaterials as scaffolds that provide structural integrity is key for tissue regeneration. In this context, hydrogels are considered a great option, due to their elastic properties and capacity to absorb large amounts of water while preserving their structure. Notably, both collagen and gelatin are considered good candidates for use due to their high biocompatibility. In particular, gelatin is a collagen derivative that has better biological properties at the expense of poorer mechanical properties. Therefore, the main objective of this work was the development and characterization of polymeric hydrogels based on collagen and gelatin. In this sense, hydrogels with different collagen/gelatin ratios were elaborated using cooling as the gelation method. Subsequently, different studies were carried out in order to evaluate their mechanical, thermal and microstructural properties, as well as their biocompatibility. The results showed that hydrogels formed from the mixture of collagen and gelatin retain, to a large extent, the good viscoelastic properties of collagen, while showing low levels of cytotoxicity and hemocompatibility similar to those obtained for gelatin. However, owing to the nature of the materials used, the thermal characteristics are not ideal for use in biomedicine, thus further studies are required to overcome these drawbacks.
Effect of different crosslinking agents on hybrid chitosan/collagen hydrogels for potential tissue engineering applications
(Elsevier, 2024-04) Sánchez Cid, Pablo; Alonso González, María; Jiménez-Rosado, Mercedes; Rafii-El-Idrissi Benhnia, Mohammed; Ruiz-Mateos Carmona, Ezequiel; Ostos Marcos, Francisco José; Romero García, Alberto; Pérez-Puyana, Víctor Manuel; Universidad de Sevilla. Departamento de Ingeniería Química; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Consejo Superior de Investigaciones Científicas (CSIC); Universidad de Sevilla. TEP229: Tecnología y Diseño de Productos Multicomponentes; Universidad de Sevilla. CTS590: Inmunovirología (Sistema Sanitario Público de Andalucía. Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI)); Universidad de Sevilla. FQM206: Grupo de Cinética del Profesor Rodríguez Velasco
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.
A lupin protein hydrolysate protects the central nervous system from oxidative stress in WD-fed ApoE
(2024) Santos Sánchez, Guillermo; Ponce España, Eduardo; Alvarez-Lopez, Ana Isabel; Pedroche, Justo; Millán Linares, María del Carmen; Fernández Pachón, María Soledad; Lardone, Patricia Judith; Cruz Chamorro, Iván; Carrillo Vico, Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Andalusian Government; Consejeria de Economia, Conocimiento, Empresas y Universidad, Junta de Andalucia; Consejeria de Salud y Familias, Junta de Andalucia; Ministerio de Educacion, Cultura y Deporte; Universidad de Sevilla
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.
Chemical and biological characterization of the DPP-IV inhibitory activity exerted by lupin (Lupinus angustifolius) peptides: From the bench to the bedside investigation
(Elsevier, 2023) Cruz-Chamorro, Ivan; Santos-Sanchez, Guillermo; Bollati, Carlotta; Bartolomei, Martina; Capriotti, Anna Laura; Cerrato, Andrea; Millán-Linares, María del Carmen; Carrillo Vico, Antonio; Lammi, Carmen; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Consejeria de Salud; Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades, Junta de Andalucia; Erasmus+ Mobility Programme; Ministerio de Economia y Competitividad, Gobierno de Espana; Ministerio de Educacion, Cultura y Deporte, Gobierno de Espana; PAIDI Program from Junta de Andalucia; Universidad de Sevilla
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.
The HLA-DQA1*05 genotype does not influence the clinical response to ustekinumab and vedolizumab
(Aran Ediciones S.A., 2023) Navajas Hernández, Pilar; Pino Bellido, Pilar del; Lorenzo González, Laura; González Rodríguez, Concepción; Pérez Pérez, Antonio; Argüelles Arias, Federico; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Medicina
Background: the success of strategies with earlier anti-TNF drugs for the treatment of inflammatory bowel disease (IBD) have been shadowed by the development of an ti-drug antibodies that reduce their effectiveness. The HLA DQA1*05 allele has been shown to increase the risk of im munogenicity to anti-TNF drugs by approximately two-fold. The negative impact of this allele has not been fully inves tigated for newer biotherapies. Objective: whether the presence of the HLA-DQA1*05 al lele is associated with a reduction of response to usteki numab and vedolizumab was investigated. Material and methods: the impact of HLA-DQA1*05 on dis ease activity in 93 patients with IBD, treated with ustekinum ab (n = 39) or vedolizumab (n = 54) was investigated in a ret rospective cohort study. Treatment response and remission was assessed at 6 and 12 months for ustekinumab, and up to 18 and 24 months for vedolizumab, using Harvey-Bradshaw index (Crohn’s disease) and Mayo score (ulcerative colitis). Results: the HLA-DQA1*05 allele was found in 35.9 % and 38.9 % of patients treated with ustekinumab and vedoli zumab, respectively. Clinical response was not affected by the presence of the HLA-DQA1*05 allele for both treat ment groups. Conclusions: in contrast to anti-TNF drugs, HLA-DQA1*05 presence does not correlate with the decreased response to ustekinumab or vedolizumab.
The Immune System in Foetal Death After a Spider Bite: Case Report with Literature Review
(Omics Publishing Group, 2016-11) Maldonado y Aibar, María Dolores; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
Loxoscelism is caused by the bite of a spider belonging to any of the Loxosceles species. We analyse the case of a pregnant woman, 35 weeks into gestation, who was accidentally bitten by a Loxosceles rufescens, in June 2015. She was treated with corticosteroids and antihistamines. After 36 hours of the bite, the patient went to Hospital having felt a lack of foetal movements. Foetal death was diagnosed and the woman was admitted for induction of labour. The autopsy stated as the cause of foetal death to be the presence of umbilical vein thrombosis and sub-funicular placental infarction. We propose that the activation of the thrombosis, in the case of this pregnancy was triggered by events linked directly with the venom of the spider. This venom possesses chemical components sufficient to activate the complement cascade which is closely linked to the coagulation system, and indirectly affected by the inflammation of the allergic response in a previously sensitized patient.
Mobile Laboratory Unit: A disruptor solution for hemostasis management during major surgery. Usage in the context of face transplantation
(Walter de Gruyter GmbH, 2012) León Justel, Antonio; Noval-Padillo, Jose Angel; Polonio, Franciso; Gomez-Cia, Tomas; Hinojosa, Rafael; Porras, Manuel; Guerrero Montávez, Juan Miguel; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
Background: The management of surgical bleeding during a face transplant in a patient diagnosed with bilateral neurofi bromatosis is quite complex. With the actual methods and technology for hemostasis management, it may not always be possible to give the clinician the support needed to manage operative associated bleeding. Bedside hemostasis monitors are needed urgently to assist clinicians in making the correct diagnosis in a timely manner. Methods: Our Mobile Laboratory Unit is a disruptive solution for hemostasis management during major surgery as it allows real-time monitoring, the predominant mechanism of bleeding and goal-direct coagulation therapy. The unit is an autonomous mobile platform that can be moved immediately to anywhere its service is needed and offers a complete fl exible laboratory test which includes biochemistry, hematology and coagulation studies as standard equipment. Results: In our case the test performed by the unit allowed us to identify the reason for our patient ’ s bleeding at the bedside. Severely decreased clot fi rmness of the fi brin-based clot and a less impaired fi rmness of the whole blood clot, suggested an acceptable contribution of platelets to the clot quality, but decreased polymerization of fi brinogen into fi brin. Conclusions: In our opinion new insights into the pathophysiology of coagulopathy, the availability of technology such as our Mobile Laboratory Unit, and awareness of side effects of intravenous fl uids should encourage the idea that perhaps it is time to change hemostasis management in operationrelated bleeding.
Complete laboratory diagnosis of Insulin Autoimmune Syndrome
(Elsevier BV, 2023) Galván, Raquel; Fernández-Riejos, Patricia; Sánchez Martínez, Pilar María; Rodríguez-Chacón, Carmen; Sánchez Mora, Catalina; León Justel, Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
The definition of Insulin autoimmune syndrome includes the presence of high levels of blood insulin and insulin autoantibodies. We encountered a 45-years-old white man with a high insulin serum value that do not fit with the C-peptide result. To discard or to confirm an analytical interference and diagnose a possible Insulin Autoimmune Syndrome we performed the following investigations: dilution linearity test, heterophilic antibody blocking, polyethylene glycol precipitation, measurements with alternative assays, and gel filtration chromatography by size exclusion. The latter technique confirmed that most of the insulin was complexed with a 150-kDa protein, corresponding to immunoglobulin G, identified as insulin autoantibodies. These antibodies were responsible for hypoglycemia attacks in the patient, who had a previous autoimmune disease. This case highlights the importance of carefully analyzing the results and ruling out possible interferences, as well as considering all kinds of pathologies, even if they are infrequent.

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