Artículos (Biología Celular)
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Artículo Hypoxia Tolerant Species: The Wisdom of Nature Translated into Targets for Stroke Therapy(MDPI, 2021-10-15) Río Mercado, Carmen del; Montaner, Joan; Universidad de Sevilla. Departamento de Biología Celular; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)Human neurons rapidly die after ischemia and current therapies for stroke management are limited to restoration of blood flow to prevent further brain damage. Thrombolytics and mechanical thrombectomy are the available reperfusion treatments, but most of the patients remain untreated. Neuroprotective therapies focused on treating the pathogenic cascade of the disease have widely failed. However, many animal species demonstrate that neurons can survive the lack of oxygen for extended periods of time. Here, we reviewed the physiological and molecular pathways inherent to tolerant species that have been described to contribute to hypoxia tolerance. Among them, Foxo3 and Eif5A were reported to mediate anoxic survival in Drosophila and Caenorhabditis elegans, respectively, and those results were confirmed in experimental models of stroke. In humans however, the multiple mechanisms involved in brain cell death after a stroke causes translation difficulties to arise making necessary a timely and coordinated control of the pathological changes. We propose here that, if we were able to plagiarize such natural hypoxia tolerance through drugs combined in a pharmacological cocktail it would open new therapeutic opportunities for stroke and likely, for other hypoxic conditions.Artículo Diet Supplementation with Polyphenol-Rich Salicornia ramosissima Extracts Protects against Tissue Damage in Experimental Models of Cerebral Ischemia(MDPI, 2022-11-29) García Rodríguez, Paula; Ma, Feifei; Río Mercado, Carmen del; Romero Bernal, Marina; Najar Moyano, Ana María; Cádiz Gurrea, María de la Luz; Montaner, Joan; Universidad de Sevilla. Departamento de Biología Celular; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de AndalucíaStrokes are the second most common cause of death worldwide and a leading cause of disability. Regular consumption of polyphenols has been shown to reduce the risk of suffering a cardiovascular event. For this reason, we have investigated the protective effect of Salicornia ramosissima, a seasonal halophyte that synthetizes high amounts of bioactive compounds, including polyphenols, in response to environmental stress. Aqueous, hydroalcoholic, and ethanolic extracts were prepared to investigate if dietary supplementation prior to ischemic challenge can prevent subsequent damage using two animal models. First, we screened the protective effect against hypoxia–reoxygenation in Drosophila melanogaster and observed that both ethanolic and hydroalcoholic extracts protected flies from the deleterious effects of hypoxia. Second, we confirmed the protective effect of S. ramosissima ethanolic extract against brain ischemia using the transient middle cerebral artery occlusion mice model. Four weeks of oral supplementation with the ethanolic extract before artery occlusion reduced infarct volume and lowered the plasma levels of the DNA peroxidant product 8-hydroxydeoxyguanosine. Phytochemical profiling of S. ramosissima ethanolic extract revealed 50 compounds. Thus, it represents a valuable source of bioactive compounds that show promising disease-modifying activities and could be further developed as an effective food supplement for the prevention or treatment of neurovascular disorders.Artículo A Review on Polyphenols in Salicornia ramosissima with Special Emphasis on Their Beneficial Effects on Brain Ischemia(MDPI, 2023-02-03) Najar Moyano, Ana María; Romero Bernal, Marina; Río Mercado, Carmen del; Montaner, Joan; Universidad de Sevilla. Departamento de Biología Celular; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de AndalucíaThere has been an increasing interest in the consumption of halophytes as a healthy food in the last few years. Salicornia ramosissima is a seasonal Mediterranean halophyte with an interesting profile of bioactive compounds, including more than 60 identified polyphenols with a broad range of biological activities. Accumulating evidence supports the role of dietary polyphenols in the prevention of cardiovascular diseases, such as stroke. Stroke is the second cause of death worldwide and it is estimated that a substantial proportion of stroke incidence and recurrence may be prevented by healthier dietary patterns. Here, we have grouped the phenolic acids and flavonoids identified in S. ramosissima and reviewed their potential protective effect on brain ischemia, which are mostly related to the reduction of oxidative stress and inflammation, the inhibition of cell death pathways and their role in the preservation of the vascular function. Despite the fact that most of these compounds have been reported to be neuroprotective through multiple mechanisms, human studies are still scarce. Given the safe profile of polyphenols identified in S. ramosissima, this halophyte plant could be considered as a source of bioactive compounds for the nutraceutical industry.Artículo LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype(Wiley, 2024-12-19) Cobo Vuilleumier, Nadia; Rodríguez Fernández, Silvia; López Noriega, Livia; Lorenzo, Petra I.; Franco, Jaime M.; Lachaud, Christian Claude; Dorronsoro, Akaitz; González Prieto, Román; Gauthier, Benoit R.; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)Background The complex aetiology of type 1 diabetes (T1D), characterised by a detrimental cross-talk between the immune system and insulin-producing beta cells, has hindered the development of effective disease-modifying therapies. The discovery that the pharmacological activation of LRH-1/NR5A2 can reverse hyperglycaemia in mouse models of T1D by attenuating the autoimmune attack coupled to beta cell survival/regeneration prompted us to investigate whether immune tolerisation could be translated to individuals with T1D by LRH-1/NR5A2 activation and improve islet survival. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from individuals with and without T1D and derived into various immune cells, including macrophages and dendritic cells. Cell subpopulations were then treated or not with BL001, a pharmacological agonist of LRH-1/NR5A2, and processed for: (1) Cell surface marker profiling, (2) cytokine secretome profiling, (3) autologous T-cell proliferation, (4) RNAseq and (5) proteomic analysis. BL001-target gene expression levels were confirmed by quantitative PCR. Mitochondrial function was evaluated through the measurement of oxygen consumption rate using a Seahorse XF analyser. Co-cultures of PBMCs and iPSCs-derived islet organoids were performed to assess the impact of BL001 on beta cell viability. Results LRH-1/NR5A2 activation induced a genetic and immunometabolic reprogramming of T1D immune cells, marked by reduced pro-inflammatory markers and cytokine secretion, along with enhanced mitohormesis in pro-inflammatory M1 macrophages and mitochondrial turnover in mature dendritic cells. These changes induced a shift from a pro-inflammatory to an anti-inflammatory/tolerogenic state, resulting in the inhibition of CD4+ and CD8+ T-cell proliferation. BL001 treatment also increased CD4+/CD25+/FoxP3+ regulatory T-cells and Th2 cells within PBMCs while decreasing CD8+ T-cell proliferation. Additionally, BL001 alleviated PBMC-induced apoptosis and maintained insulin expression in human iPSC-derived islet organoids. Conclusion These findings demonstrate the potential of LRH-1/NR5A2 activation to modulate immune responses and support beta cell viability in T1D, suggesting a new therapeutic approach.Artículo Evaluation of Bioactive Effects of Five Plant Extracts with Different Phenolic Compositions against Different Therapeutic Targets(MDPI, 2024-02-08) Villegas Aguilar, María del Carmen; Sánchez Marzo, Noelia; Río Mercado, Carmen del; Montaner, Joan; Micol, Vicente; Fernández Ochoa, Álvaro; Segura Carretero, Antonio; Universidad de Sevilla. Departamento de Biología Celular; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)Plant extracts rich in phenolic compounds have been reported to exert different bioactive properties. Despite the fact that there are plant extracts with completely different phenolic compositions, many of them have been reported to have similar beneficial properties. Thus, the structure–bioactivity relationship mechanisms are not yet known in detail for specific classes of phenolic compounds. In this context, this work aims to demonstrate the relationship of extracts with different phenolic compositions versus different bioactive targets. For this purpose, five plant matrices (Theobroma cacao, Hibiscus sabdariffa, Silybum marianum, Lippia citriodora, and Olea europaea) were selected to cover different phenolic compositions, which were confirmed by the phytochemical characterization analysis performed by HPLC-ESI-qTOF-MS. The bioactive targets evaluated were the antioxidant potential, the free radical scavenging potential, and the inhibitory capacity of different enzymes involved in inflammatory processes, skin aging, and neuroprotection. The results showed that despite the different phenolic compositions of the five matrices, they all showed a bioactive positive effect in most of the evaluated assays. In particular, matrices with very different phenolic contents, such as T. cacao and S. marianum, exerted a similar inhibitory power in enzymes involved in inflammatory processes and skin aging. It should also be noted that H. sabdariffa and T. cacao extracts had a low phenolic content but nevertheless stood out for their bioactive antioxidant and anti-radical capacity. Hence, this research highlights the shared bioactive properties among phenolic compounds found in diverse matrices. The abundance of different phenolic compound families highlights their elevated bioactivity against diverse biological targets.Artículo Evaluating the Clinical Impact of a Polyphenol-Rich Extract from Salicornia ramosissima on Patients with Transient Ischemic Attack and Minor Stroke(MDPI, 2024-12-13) Najar Moyano, Ana María; López Azcárate, Cristina; Domínguez Ruiz, Carmen; Núñez Jurado, David; Torres, Reyes de; López, Reyes; Camino Moya, Miriam; Magni, Eleonora; Río Mercado, Carmen del; Pérez Sánchez, Soledad; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Enfermería; European Union (UE); Instituto de Salud Carlos III; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Ministerio de Sanidad. EspañaTransient ischemic attack (TIA) is a well-established risk factor for future strokes, making interventions that target recovery and vascular risk crucial. This study aimed to assess the safety and clinical effects of a polyphenol-rich Salicornia ramosissima extract in post-TIA patients. A randomized, triple-blind, placebo-controlled trial was conducted with participants who had a history of TIA or minor stroke and who received 1 g of Salicornia extract or placebo over 11 months. Biochemical analyses, neuropsychological assessments (MOCA test), and gait and aerobic performance tests were conducted at the beginning and the end of the study. A total of 118 individuals were screened, with 80 finally included. Importantly, no significant adverse events were reported throughout the study. A neurological analysis showed an improvement in MOCA scores in patients treated with the Salicornia extract for 11 months. The treatment did not affect spatiotemporal gait parameters, but it significantly reduced blood pressure at baseline and after the aerobic performance test. Biochemically, both groups exhibited mild hyperhomocysteinemia at baseline; however, Salicornia treatment significantly lowered homocysteine levels, bringing them within the normal range. These findings highlight the safety of the Salicornia extract in patients at a high cerebrovascular risk and suggest it as a potential therapeutic option for managing vascular risk factors, such as hyperhomocysteinemia and hypertension. However, further studies are required to confirm the underlying mechanisms and explore broader clinical applications.Artículo Dietary supplementation with polyphenol-rich Salicornia ramosissima extracts: Assessing safety, efficacy, and impact on cardiovascular health biomarkers in healthy volunteers(MDPI, 2024-10-30) Najar Moyano, Ana María; Pérez Sánchez, Soledad; Río Mercado, Carmen del; Domínguez, Carmen; López Azcárate, Cristina; Torres, Reyes de; Montaner, Joan; Universidad de Sevilla. Departamento de Biología Celular; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Ministerio de Sanidad. EspañaThe importance of diet in preventing non-communicable diseases is well established, with polyphenol consumption suggested to impact cardiovascular disease development. Salicornia ramosissima synthesizes high amounts of phytochemicals under environmental stress. In a randomized controlled clinical trial on 90 healthy volunteers, we evaluated the safety of supplementation with 1 g of polyphenol-rich S. ramosissima extracts from salt marshes and hydroponic sources over three months. No differences in adverse effects were observed between extract-treated and placebo subjects. Salicornia extract from marshes (SM) increased glomerular filtration rate and reduced LDL cholesterol. SM treatment also modulated plasma markers related to cardiovascular disease: MERTK, Gal-9, ADM, TF, PRSS27, HAOX1, IL-18, PAPPA, TNFRSF1A, TIE2 and FGF-21 proteins were downregulated while SRC levels were upregulated. Therefore, under the studied conditions of use, Salicornia extracts consumption is safe and SM induced biochemical and proteomic changes related to cardiovascular health.Artículo Distinct UPR and Autophagic Functions Define Cell-Specific Responses to Proteotoxic Stress in Microglial and Neuronal Cell Lines(MDPI, 2024-12-15) Domínguez Martín, Helena; Gavilán Dorronzoro, Elena; Parrado, Celia; Burguillos García, Miguel Ángel; Daza Navarro, María Paula; Ruano Caballero, Diego; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Junta de Andalucía; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; Unión Europea NextGeneration; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Universidad de Sevilla. CTS257: Envejecimiento y Neurodegeneración.first_pagesettingsOrder Article Reprints Open AccessArticle Distinct UPR and Autophagic Functions Define Cell-Specific Responses to Proteotoxic Stress in Microglial and Neuronal Cell Lines by Helena Domínguez-Martín 1,2,†,Elena Gavilán 1,2,†ORCID,Celia Parrado 1,Miguel A. Burguillos 1,2ORCID,Paula Daza 3 andDiego Ruano 1,2,* 1 Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla (US), 41012 Sevilla, Spain 2 Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Sevilla (US), 41013 Sevilla, Spain 3 Departamento de Biología Celular, Facultad de Biología, Universidad de Sevilla (US), 41012 Sevilla, Spain * Author to whom correspondence should be addressed. † These authors contributed equally to this work and share first authorship. Cells 2024, 13(24), 2069; https://doi.org/10.3390/cells13242069 Submission received: 4 November 2024 / Revised: 10 December 2024 / Accepted: 13 December 2024 / Published: 15 December 2024 (This article belongs to the Special Issue Understanding the Interplay Between Autophagy and Neurodegeneration) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract Autophagy is a catabolic process involved in different cellular functions. However, the molecular pathways governing its potential roles in different cell types remain poorly understood. We investigated the role of autophagy in the context of proteotoxic stress in two central nervous system cell types: the microglia-like cell line BV2 and the neuronal-like cell line N2a. Proteotoxic stress, induced by proteasome inhibition, produced early apoptosis in BV2 cells, due in part to a predominant activation of the PERK-CHOP pathway. In contrast, N2a cells showcased greater resistance and robust induction of the IRE1α-sXbp1 arm of the UPR. We also demonstrated that proteotoxic stress activated autophagy in both cell lines but with different kinetics and cellular functions. In N2a cells, autophagy restored cellular proteostasis, while in BV2 cells, it participated in regulating phagocytosis. Finally, proteotoxic stress predominantly activated the mTORC2-AKT-FOXO1-β-catenin pathway in BV2 cells, while N2a cells preferentially induced the PDK1-AKT-FOXO3 axis. Collectively, our findings suggest that proteotoxic stress triggers cell-specific responses in microglia and neurons, with different physiological outcomes.Artículo Hyperhomocysteinemia: Underlying Links to Stroke and Hydrocephalus, with a Focus on Polyphenol-Based Therapeutic Approaches(Multidisciplinary Digital Publishing Institute (MDPI), 2024-12-26) Ortiz Salguero, Carmen; Romero Bernal, Marina; González Díaz, Ángela; Doush, Elaheh Sobh; Río Mercado, Carmen del; Echevarría Irusta, Miriam; Montaner, Joan; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Instituto de Salud Carlos III; Ministerio de Economía y Competitividad (MINECO). España; Junta de AndalucíaHyperhomocysteinemia (HHcy), characterized by elevated homocysteine (HCys) levels, is associated with increased risks of neurovascular diseases such as stroke or hydrocephalus. HHcy promotes oxidative stress, neuroinflammation, and endothelial dysfunction, disrupting the blood–brain barrier and accelerating neurodegeneration. These processes highlight HCys as both a biomarker and a potential therapeutic target in vascular-related neurological disorders. Current research suggests that polyphenols, known for their antioxidant and anti-inflammatory properties, may reduce HCys levels and offer neuroprotection. Polyphenols have demonstrated effectiveness in modulating oxidative stress and inflammatory pathways triggered by HHcy. These compounds may also upregulate enzymatic functions involved in HCys metabolism, thus reducing neurotoxicity. Furthermore, polyphenol-rich diets, like the Mediterranean diet, have been linked to lower HCys levels and a reduced incidence of neurovascular disorders. This review provides an overview of HHcy’s role in neurovascular pathologies and examines the therapeutic potential of polyphenols in managing HCys levels and preventing HCys-induced neurovascular damage.Artículo Absence of Aquaporin-4 (AQP4) Prolongs the Presence of a CD11c+ Microglial Population during Postnatal Corpus Callosum Development(Multidisciplinary Digital Publishing Institute (MDPI), 2024-07-30) Mayo Leon, Francisco; González Vinceiro, Lourdes; Hiraldo González, Laura; Calle Castillejo, Claudia; Torres Rubio, Ismael; Mayo León, Manuel; Ramírez Lorca, Reposo; Echevarría Irusta, Miriam; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Física Atómica, Molecular y Nuclear; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Ministerio de Economía y Competitividad (MINECO). España; Junta de AndalucíaAquaporin-4 (AQP4) expression is associated with the development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed a modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells was overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect. Here, we verified the location of this CD11c+ expression in the corpus callosum (CC) and cerebellum of AQP4-KO mice and analysed its time course. Immunofluorescence labelling of the CD11c protein in the CC and cerebellum of WT and KO animals at P3, P5, P7 and P11 confirmed an expanded presence of these cells in both tissues of the KO animal; CD11c+ cells appeared at P3 and reached a peak at P11, whereas in the WT animal, they appeared at P5, reached their peak at P7 and were undetectable by P11. The gene expression analysis in the CC samples at P11 confirmed the presence of CD11c+ microglial cells in this tissue. Among the more than 4000 overexpressed genes, Spp1 stood out with the highest differential gene expression (≅600), with other genes, such as Gpnmb, Itgax, Cd68 and Atp6v0d2, also identified as overexpressed. Therefore, CD11c+ cells appear to be necessary for normal corpus callosum development during postnatal life, and the absence of AQP4 prolonged its expression in this tissue.Artículo The Coffee Constituent Chlorogenic Acid Induces Cellular DNA Damage and Formation of Topoisomerase I– and II–DNA Complexes in Cells(American Chemical Society, 2012-07-13) Burgos Morón, Estefanía; Calderón Montaño, José Manuel; Orta Vázquez, Manuel Luis; Pastor Carrillo, Nuria María; Pérez Guerrero, María Concepción; Austin, Caroline; Mateos Cordero, Santiago; López Lázaro, Miguel; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Biología CelularChlorogenic acid (CGA) is a plant polyphenol with known antioxidant properties. Although some studies suggest that CGA has anticancer properties, others indicate that this dietary constituent may cause DNA damage and induce carcinogenic effects. Because CGA is widely consumed in the form of coffee, it is important to further evaluate the putative DNA-damaging activity of CGA. Here we have employed two standard techniques commonly used for DNA damage detection (the comet assay and the γ- H2AX focus assay) and observed that CGA (0.5–5 mM) induces DNA damage in normal and cancer cells. We report for the first time that CGA induces high levels of topoisomerase I- and topoisomerase II-DNA complexes in cells (TARDIS assay). Catalase pretreatment abolished the formation of these topoisomerase-DNA complexes and reduced the cytotoxic activity of CGA, therefore indicating that hydrogen peroxide plays an important role in these activities. Lung cancer cells (A549) were more sensitive than normal lung fibroblasts (MRC5) to the cytotoxic activity of CGA, supporting previous findings that CGA may induce selective killing of cancer cells. Taking into consideration our results and the pharmacokinetic profile of CGA, the possible cancer preventive, carcinogenic and therapeutic potential of this dietary agent are discussed.Artículo Selective cytotoxic activity of new lipophilic hydroxytyrosol alkyl ether derivatives(American Chemical Society, 2013-05-02) Calderón Montaño, José Manuel; Madrona, Andrés; Burgos Morón, Estefanía; Orta Vázquez, Manuel Luis; Mateos Cordero, Santiago; Espartero Sánchez, José Luis; López Lázaro, Miguel; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Junta de AndalucíaRecent data suggest that hydroxytyrosol, a phenolic compound of virgin olive oils, has anticancer activity. This communication reports the synthesis of decyl and hexadecyl hydroxytyrosyl ethers, as well as the cytotoxic activity of hydroxytyrosol and a series of seven hydroxytyrosol alkyl ether derivatives against A549 lung cancer cells and MRC5 non-malignant lung fibroblasts. Hydroxytyrosyl dodecyl ether (HTDE) showed the highest selective cytotoxicity, and possible mechanisms of action were investigated; results suggest that HTDE can moderately inhibit glycolysis, induce oxidative stress, and cause DNA damage in A549 cells. The combination of HTDE with the anticancer drug 5-fluorouracil induced a synergistic cytotoxicity in A549 cancer cells but not in non-malignant MRC5 cells. HTDE also displayed selective cytotoxicity against MCF7 breast cancer cells versus MCF10 normal breast epithelial cells in the 1-30 μM range. These results suggest that the cytotoxicity of HTDE is more potent and selective than that of parent compound hydroxytyrosol.Artículo Three double-dose reinforced hepatitis B revaccination scheme for patients with cirrhosis unresponsive to the standard regimen: an open-label randomised clinical trial(BMJ Publishing Group, 2023-03-24) Giráldez Gallego, Álvaro; Rodríguez Seguel, Elisa del Pilar; Valencia, R.; Morillo García, Áurea; Salamanca Rivera, Celia; Ruiz Pérez, Ricardo; Praena Fernández, Juan Manuel; Cuaresma Duque, María; Ferrer Ríos, María Teresa; Sousa Martín, José Manuel; Gasch Illescas, Antonia; Ampuero Herrojo, Javier; Pascasio Acevedo, Juan Manuel; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Medicina; Instituto de Salud Carlos IIIObjective We aimed to compare the response rates between two different hepatitis B virus vaccination schedules for cirrhotic subjects who were non-responders to the first three 40 µg doses (month 0-1-2), and identify factors associated with the final response. Design A total of 120 cirrhotic patients (72.5% decompensated) were randomised at a 1:1 ratio to receive a single 40 µg booster vaccination at month 6 (classical arm) versus an additional round of three new 40 µg doses administered at monthly intervals (experimental arm). The main outcome was the rate of postvaccinal anti-hepatitis B surface antibodies levels ≥10 mIU/mL. Results Efficacy by ITT analysis was higher in the experimental arm (46.7%) than in the classical one (25%); OR 2.63, p=0.013. The experimental arm increased response rates compared with the classical one from 31% to 68% (OR 4.72; p=0.007), from 24.4% to 50% (OR 3.09; p=0.012) and from 24.4% to 53.8% (OR 3.62; p=0.007), in Child A, Model for End-Stage Liver Disease (MELD) <15 and MELD-Na<15 patients, respectively. Patients with more advanced liver disease did not benefit from the reinforced scheme. Both regimens showed similar safety profiles. Multivariable analysis showed that the experimental treatment was independently response associated when adjusted across three logistic regression models indicating equivalent cirrhosis severity. Conclusion For cirrhotic patients, the revaccination of non-responders to the first three dose cycle, with three additional 40 µg doses, achieved significantly better response rates to those obtained with an isolated 40 µg booster dose.Artículo Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure(2024-10) Puente, A.; Fortea, José Ignacio; Pozo, C. del; Serrano, M.; Alonso Peña, M.; Giráldez, A.; Rodríguez Seguel, Elisa del Pilar; Crespo, J.; Universidad de Sevilla. Departamento de Biología CelularBackground and aims Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. Methods We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. Results 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48–133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71–23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. Conclusion The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.Artículo Bioimpedance Spectroscopy-Based Edema Supervision Wearable System for Noninvasive Monitoring of Heart Failure(Institute of Electrical and Electronics Engineers, 2023-05-17) Fernández Scagliusi, Santiago Joaquín; Giménez Miranda, Luis; Pérez García, Pablo; Martín Fernández, Daniel; Medrano Ortega, Francisco Javier; Huertas Sánchez, Gloria; Yúfera García, Alberto; Universidad de Sevilla. Departamento de Tecnología Electrónica; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Electrónica y Electromagnetismo; Universidad de Sevilla. Departamento de Biología Celular; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Instituto de Salud Carlos IIIHeart failure (HF) is a complex syndrome in which the heart is unable to pump enough blood containing oxygen and nutrients to meet the body's demands. HF is the leading cause of hospitalization for patients over 65 years of age. After a patient is diagnosed with HF, the mortality rate is 50% within the first five years. Presently, there are no unanimous diagnostic criteria for HF. Bioimpedance (BI) analysis has been proposed in recent years as a technique to detect one of the main symptoms: changes in body volume due to edema. This research presents a portable device (Volum), capable of performing real-time BI measurements in a low-cost and noninvasive way. The goal is to improve patient monitoring at home to ensure rapid intervention in cases of worsening conditions, either with timely hospitalizations or adjustments to a patient's usual treatment. Volum is a small, wearable, wireless, lightweight, low-power clinical pilot prototype that takes measurements through four electrodes and sends the data via Bluetooth to an Android device.Artículo Monounsaturated fatty acids in a high-fat diet and niacin protect from white fat dysfunction in the metabolic syndrome(WILEY, 2019) Montserrat de la Paz, Sergio; Naranjo, Maria C.; Millán Linares, María del Carmen; López Martín, Sergio; Abia, Rocio; Biessen, Erik A.L.; Muriana, Francisco J.G.; Bermúdez Pulgarín, Beatriz; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Biología Celular; Instituto de Biomedicina de Sevilla (IBIS); Gobierno de España; Consejo Superior de Investigaciones Científicas (CSIC); Universidad de Sevilla. CTS1074: InmunoNutrición e InmunoMetabolismo.; Universidad de Sevilla. BIO271: Expresión génica en eucariontes.; Universidad de Sevilla. BIO132: Citoquímica ultraestructural.Scope: Obesity is a principal causative factor of metabolic syndrome. Niacin potently regulates lipid metabolism. Replacement of saturated fatty acids by MUFAs or inclusion of omega-3 long-chain PUFAs in the diet improves plasma lipid levels. However, the potential benefits of niacin in combination with MUFAs or omega-3 long-chain PUFAs against white adipose tissue (WAT) dysfunction in the high fat diet (HFD)-induced metabolic syndrome are unknown. Methods and results: Male Lepob/ob LDLR-/- mice are fed a chow diet or HFDs based on milk cream (21% kcal), olive oil (21% kcal), or olive oil (20% kcal) plus 1% kcal from eicosapentaenoic and docosahexaenoic acids, including immediate-release niacin (1% w/v) in drinking water, for 8 weeks. Mice are then phenotyped. Dietary MUFAs are identified as positive regulators of adipose NAD+ signaling pathways by triggering NAD+ biosynthesis via the salvage pathway. This coexists with overexpression of genes involved in recognition of NAD+ and fatty acids, a surrounding lipid environment dominated by exogenous oleic acid and an alternatively activated macrophage profile, which culminate in a healthy expansion of WAT and improvement of several hallmarks that typify the metabolic syndrome. Conclusion: Niacin in combination with dietary MUFAs can favor WAT homeostasis in the development of HFD-induced obesity and metabolic syndrome.Artículo Importance of hydrophobic interactions in the single-chained cationic surfactant-DNA complexation(Elsevier, 2018-07-01) López-López, Manuel; López-Cornejo, María del Pilar; Martín, Victoria I.; Ostos Marcos, Francisco José; Checa Rodríguez, Cintia; Prados Carvajal, Rosario; Lebrón Romero, José Antonio; Huertas Sánchez, Pablo; Moyá Morán, María Luisa; Universidad de Sevilla. Departamento de Química Física; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Genética; Junta de Andalucía; Universidad de Sevilla; Ministerio de Economía y Competitividad (MINECO). EspañaThe goal of this work was to understand the key factors determining the DNA compacting capacity of single-chained cationic surfactants. Fluorescence, zeta potential, circular dichroism, gel electrophoresis and AFM measurements were carried out in order to study the condensation of the nucleic acid resulting from the formation of the surfactant-DNA complexes. The apparent equilibrium binding constant of the surfactants to the nucleic acid, Kapp, estimated from the experimental results obtained in the ethidium bromide competitive binding experiments, can be considered directly related to the ability of a given surfactant as a DNA compacting agent. The plot of ln(Kapp) vs. ln(cmc), cmc being the critical micelle concentration, for all the bromide and chloride surfactants studied, was found to be a reasonably good linear correlation. This result shows that hydrophobic interactions mainly control the surfactant DNA compaction efficiencyArtículo Low cost SU-8 lift-off process to fabricate a gold/glass microelectrodes array for culturing applications(Springer Science, 2021-01-09) Cabello Valverde, Miguel; Domínguez García, Inmaculada; Macías Zabala, Clara; Perdigones Sánchez, Francisco; Aracil Fernández, Carmen; Quero Reboul, José Manuel; Universidad de Sevilla. Departamento de Ingeniería Electrónica; Universidad de Sevilla. Departamento de Biología Celular; Ministerio de Economía y Competitividad (MINECO). EspañaIn this paper, a procedure to release SU-8 layers from glass substrates using typical undesirable effects is described. The proposed process can be used as lift off or stripping. The releasing method consists in taking advantage of the undesired thermal delamination, and the effect of UV overexposure on the delamination temperature, which are considered undesirable effects. This implies the use of SU-8 for both structural and lift off using the same facilities, without any additional photoresist, material, remover or developer. In this way, the fabrication of a glass/gold microelectrodes array (MEA) for cell culture applications is carried out as a proof of concept. The MEA is composed of gold tracks of 1.5 mm width and 8 electrodes with radii between 25 and 500 μ m at its ends. The SU-8 photoresist is also used as an insulation layer releasing the pads and the electrodes. Finally, biological experiments with neuroblastoma cells SK-N-SH cultured on the MEA surface were carried out in order to validate and demonstrate the biocompatibility of both the MEA and the process. The fabrication and biological results were successful, showing a normal cell proliferation over the developed MEAArtículo Proteomic analysis of postprandial high-density lipoproteins in healthy subjects(Elsevier, 2022-12-27) Grao Cruces, Elena; Santos-Mejías, Alejandro; Ortea, Ignacio; Márquez Paradas, Elvira; Martín Rubio, María Esther; Barrientos Trigo, Sergio; Bermúdez Pulgarín, Beatriz; Montserrat de la Paz, Sergio; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Enfermería; Junta de Andalucía; European Union (UE)The relationship between the functionality and composition of high-density lipoproteins (HDL) is yet not fully studied, and little is known about the influence of the diet in HDL proteome. Therefore, the aim of this research was to elucidate the HDL proteome associated to postprandial hyperlipidemia. Male volunteers were recruited for an interventional study with high fatty acid-based meals. Blood samples were collected before the intake (baseline), and 2–3 (postprandial peak) and 5–6 (postprandial post peak) hours later. HDL were purified and the protein composition was quantified by LC-MS/MS. Statistical analysis was performed by lineal models (amica) and by ANOVA and multi-t-test of the different conditions (MetaboAnalyst). Additionally, a clustering of the expression profiles of each protein was done with coseq R package (RStudio). Initially, 320 proteins were identified but only 119 remained after the filtering. APOM, APOE, APOB, and APOA2, proteins previously identified in the HDL proteome, were the only proteins with a statistically significant altered expression in postprandial hyperlipidemia when compared to baseline (p values <0.05 and logFC >1). In conclusion, we have been able to describe several behaviors of the whole HDL proteome during the postprandial hyperlipidemic metabolism.Artículo Kiwicha (Amaranthus caudatus L.) protein hydrolysates reduce intestinal inflammation by modulating the NLRP3 inflammasome pathway(Royal Society of Chemistry, 2022-10-10) Rivero-Pino, Fernando; Toscano Sánchez, María del Rocío; Grao Cruces, Elena; Márquez Paradas, Elvira; Montserrat de la Paz, Sergio; Martínez López, Alicia; Villanueva Lazo, Álvaro; Martín Rubio, María Esther; Millán Linares, María del Carmen; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Junta de Andalucía; European Union (UE)The increase in the world population along with new policies aimed at a more sustainable world has led to the need of searching for new food sources, which are environmentally friendly, implying healthy and nutritious diets. This study explored the biological activity of two kiwicha (Amaranthus caudatus L.) protein hydrolysates obtained with the aid of Bioprotease LA-660 regarding their anti-inflammatory response at the intestinal level, employing the CACO-2 cell line. The results obtained showed that the in vitro administration of these hydrolysates decreased the expression of proinflammatory cytokines, increased the expression of anti-inflammatory cytokines, and decreased the gene expression of the major components of inflammasomes in the intestinal CACO-2 cell model. To the best of our knowledge, this is the first study involving the evaluation of the anti-inflammatory activity of kiwicha hydrolysates at the intestinal level, employing the CACO-2 cell model and its ultrastructural characterization using scanning electron microscopy. We conclude that the Amaranthus caudatus hydrolysates are a valuable source of active peptides that take part as functional ingredients in food and nutraceutical preparations.