Artículos (Bioquímica y Biología Molecular)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/10995

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A New Biostimulant Derived from Soybean by-products Enhances Plant Tolerance to Abiotic Stress Triggered by Ozone
(Springer Nature, 2024) Orts, A.; Navarro Torre, Salvadora; Macías Benitez, S.; Orts Gómez, José María; Naranjo Fernández, Emilia; Castaño Navarro, Angélica; Parrado Rubio, Juan; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Microbiología y Parasitología; Ministerio de Ciencia e Innovación (MICIN). España
Background: Tropospheric ozone is an air pollutant that causes negative effects on vegetation, leading to significant losses in crop productivity. It is generated by chemical reactions in the presence of sunlight between primary pollutants resulting from human activity, such as nitrogen oxides and volatile organic compounds. Due to the constantly increasing emission of ozone precursors, together with the influence of a warming climate on ozone levels, crop losses may be aggravated in the future. Therefore, the search for solutions to mitigate these losses becomes a priority. Ozone-induced abiotic stress is mainly due to reactive oxygen species generated by the spontaneous decomposition of ozone once it reaches the apoplast. In this regard, compounds with antioxidant activity offer a viable option to alleviate ozone-induced damage. Using enzymatic technology, we have developed a process that enables the production of an extract with biostimulant properties from okara, an industrial soybean byproduct. The biostimulant, named as OEE (Okara Enzymatic Extract), is water-soluble and is enriched in bioactive compounds present in okara, such as isoflavones. Additionally, it contains a significant fraction of protein hydrolysates contributing to its functional effect. Given its antioxidant capacity, we aimed to investigate whether OEE could alleviate ozone-induced damage in plants. For that, pepper plants (Capsicum annuum) exposed to ozone were treated with a foliar application of OEE. Results: OEE mitigated ozone-induced damage, as evidenced by the net photosynthetic rate, electron transport rate, effective quantum yield of PSII, and delayed fluorescence. This protection was confirmed by the level of expression of genes associated with photosystem II. The beneficial effect was primarily due to its antioxidant activity, as evidenced by the lipid peroxidation rate measured through malondialdehyde content. Additionally, OEE triggered a mild oxidative response, indicated by increased activities of antioxidant enzymes in leaves (catalase, superoxide dismutase, and guaiacol peroxidase) and the oxidative stress index, providing further protection against ozone-induced stress. Conclusions: The present results support that OEE protects plants from ozone exposure. Taking into consideration that the promotion of plant resistance against abiotic damage is an important goal of biostimulants, we assume that its use as a new biostimulant could be considered.
In Vivo PET Detection of Lung Micrometastasis in Mice by Targeting Endothelial VCAM-1 Using a Dual-Contrast PET/MRI Probe
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-06-28) Melemenidis, Stavros; Knight, James C.; Kersemans, Veerle; Perez-Balderas, Francisco; Zarghami, Niloufar; Sarmiento Soto, Manuel; Sibson, Nicola R.; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Cancer Research UK (CRUK); Comprehensive Cancer Imaging Centre (CCIC)
Current clinical diagnostic imaging methods for lung metastases are sensitive only to large tumours (1–2 mm cross-sectional diameter), and early detection can dramatically improve treatment. We have previously demonstrated that an antibody-targeted MRI contrast agent based on microparticles of iron oxide (MPIO; 1 μm diameter) enables the imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Using a mouse model of lung metastasis, upregulation of endothelial VCAM-1 expression was demonstrated in micrometastasis-associated vessels but not in normal lung tissue, and binding of VCAM-MPIO to these vessels was evident histologically. Owing to the lack of proton MRI signals in the lungs, we modified the VCAM-MPIO to include zirconium-89 (89Zr, t1/2 = 78.4 h) in order to allow the in vivo detection of lung metastases by positron emission tomography (PET). Using this new agent (89Zr-DFO-VCAM-MPIO), it was possible to detect the presence of micrometastases within the lung in vivo from ca. 140 μm in diameter. Histological analysis combined with autoradiography confirmed the specific binding of the agent to the VCAM-1 expressing vasculature at the sites of pulmonary micrometastases. By retaining the original VCAM-MPIO as the basis for this new molecular contrast agent, we have created a dual-modality (PET/MRI) agent for the concurrent detection of lung and brain micrometastases.
Direct Interaction between Marine Cyanobacteria Mediated by Nanotubes
(American Association for the Advancement of Science, 2024) Angulo Cánovas, Elisa; Bartual, Ana; López Igual, Rocío; Luque, Ignacio; Radzinski, Nikolai P.; Shilova, Irina; Anjur Dietrich, Maya; García Jurado, Gema; Úbeda, Bárbara; González Reyes, José Antonio; Muñoz Marín, María del Carmen; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Gobierno de España; Ministerio de Ciencia e Innovación (MICIN). España; Simons Foundation Life Sciences; SCOPE Award; Simons Postdoctoral Fellowship in Marine Microbial Ecology; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Frontier Projects
Microbial associations and interactions drive and regulate nutrient fluxes in the ocean. However, physical contact between cells of marine cyanobacteria has not been studied thus far. Here, we show a mechanism of direct interaction between the marine cyanobacteria Prochlorococcus and Synechococcus, the intercellular membrane nanotubes. We present evidence of inter-and intra-genus exchange of cytoplasmic material between neighboring and distant cells of cyanobacteria mediated by nanotubes. We visualized and measured these structures in xenic and axenic cultures and in natural samples. We show that nanotubes are produced between living cells, suggesting that this is a relevant system of exchange material in vivo. The discovery of nanotubes acting as exchange bridges in the most abundant photosynthetic organisms in the ocean may have important implications for their interactions with other organisms and their population dynamics.
Dopaminergic neurons lacking Caspase-3 avoid apoptosis but undergo necrosis after MPTP treatment inducing a Galectin-3-dependent selective microglial phagocytic response
(Springer Nature, 2024-08-27) García Revilla, Juan; Ruiz Laza, Rocío; Espinosa Oliva, Ana María; Santiago Pavón, Martiniano; García Domínguez, Irene; Camprubí Ferrer, Lluís; Bachiller Sánchez Arévalo, Sara; Deierborg, Tomas; Joseph, Bertrand; Martínez de Pablos, Rocío; Rodríguez Gómez, José Antonio; Venero Recio, José Luis; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc). Apoptosis is thought to play a critical role in the progression of PD, and thus understanding the effects of antiapoptotic strategies is crucial for developing potential therapies. In this study, we developed a unique genetic model to selectively delete Casp3, the gene encoding the apoptotic protein caspase-3, in dopaminergic neurons (TH-C3KO) and investigated its effects in response to a subacute regime of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, which is known to trigger apoptotic loss of SNpc dopaminergic neurons. We found that Casp3 deletion did not protect the dopaminergic system in the long term. Instead, we observed a switch in the cell death pathway from apoptosis in wild-type mice to necrosis in TH-C3KO mice. Notably, we did not find any evidence of necroptosis in our model or in in vitro experiments using primary dopaminergic cultures exposed to 1-methyl-4-phenylpyridinium in the presence of pan-caspase/caspase-8 inhibitors. Furthermore, we detected an exacerbated microglial response in the ventral mesencephalon of TH-C3KO mice in response to MPTP, which mimicked the microglia neurodegenerative phenotype (MGnD). Under these conditions, it was evident the presence of numerous microglial phagocytic cups wrapping around apparently viable dopaminergic cell bodies that were inherently associated with galectin-3 expression. We provide evidence that microglia exhibit phagocytic activity towards both dead and stressed viable dopaminergic neurons through a galectin-3-dependent mechanism. Overall, our findings suggest that inhibiting apoptosis is not a beneficial strategy for treating PD. Instead, targeting galectin-3 and modulating microglial response may be more promising approaches for slowing PD progression.
Microglia mitochondrial complex I deficiency during development induces glial dysfunction and early lethality
(Nature, 2024-07-24) Mora Romero, Bella; Capelo Carrasco, Nicolás; Pérez Moreno, Juan José; Álvarez Vergara, María Isabel; Trujillo Estrada, Laura Isabel; Romero Molina, Carmen; Martínez Márquez, Emilio; Morano Catalan, Noelia; Vizuete Chacón, María Luisa; López Barneo, José; Nieto González, José Luis; García-Junco Clemente, Pablo; Vitorica Ferrández, Francisco Javier; Gutiérrez, Antonia; Macías, David; Rosales Nieves, Alicia E.; Pascual Bravo, Alberto; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía
Primary mitochondrial diseases (PMDs) are associated with pediatric neurological disorders and are traditionally related to oxidative phosphorylation system (OXPHOS) defects in neurons. Interestingly, both PMD mouse models and patients with PMD show gliosis, and pharmacological depletion of microglia, the innate immune cells of the brain, ameliorates multiple symptoms in a mouse model. Given that microglia activation correlates with the expression of OXPHOS genes, we studied whether OXPHOS deficits in microglia may contribute to PMDs. We first observed that the metabolic rewiring associated with microglia stimulation in vitro (via IL-33 or TAU treatment) was partially changed by complex I (CI) inhibition (via rotenone treatment). In vivo, we generated a mouse model deficient for CI activity in microglia (MGcCI). MGcCI microglia showed metabolic rewiring and gradual transcriptional activation, which led to hypertrophy and dysfunction in juvenile (1-month-old) and adult (3-month-old) stages, respectively. MGcCI mice presented widespread reactive astrocytes, a decrease of synaptic markers accompanied by an increased number of parvalbumin neurons, a behavioral deficit characterized by prolonged periods of immobility, loss of weight and premature death that was partially rescued by pharmacologic depletion of microglia. Our data demonstrate that microglia development depends on mitochondrial CI and suggest a direct microglial contribution to PMDs.
Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth
(Elsevier, 2024-04-16) Rivera Ramos, Alberto; Cruz Hernández, Luis; Talaverón Aguilocho, Rocío; Sánchez Montero, María Teresa; García Revilla, Juan; Mulero Acevedo, Marta; Deierborg, Tomas; Venero Recio, José Luis; Sarmiento Soto, Manuel; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; European Union (UE); Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España
Galectin-3 (Gal-3) is a multifunctional protein that plays a pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although the involvement of Gal-3 in tumour progression, resistance to treatment and immunosuppression has long been studied in different cancer types, mainly outside the central nervous system, its elevated expression in myeloid and glial cells underscores its profound impact on the brain's immune response. In this context, microglia and infiltrating macrophages, the predominant non-cancerous cells within the tumour microenvironment, play critical roles in establishing an immunosuppressive milieu in diverse brain tumours. Through the utilisation of primary cell cultures and immortalised microglial cell lines, we have elucidated the central role of Gal-3 in promoting cancer cell migration, invasion, and an immunosuppressive microglial phenotypic activation. Furthermore, employing two distinct in vivo models encompassing primary (glioblastoma) and secondary brain tumours (breast cancer brain metastasis), our histological and transcriptomic analysis show that Gal-3 depletion triggers a robust pro-inflammatory response within the tumour microenvironment, notably based on interferon-related pathways. Interestingly, this response is prominently observed in tumour-associated microglia and macrophages (TAMs), resulting in the suppression of cancer cells growth.
Update on modifiable risk factors for Alzheimer’s disease and related dementias
(Wolters Kluwer, 2024) Jaisa Aad, Methasit; Muñoz Castro, Clara; Serrano Pozo, Alberto; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; National Institutes on Aging. United States
Purpose of review. All human beings undergo a lifelong cumulative exposure to potentially preventable adverse factors such as toxins, infections, traumatisms, and cardiovascular risk factors, collectively termed exposome. The interplay between the individual’s genetics and exposome is thought to have a large impact in health outcomes such as cancer and cardiovascular disease. Likewise, a growing body of evidence is supporting the idea that preventable factors explain a sizable proportion of Alzheimer’s disease and related dementia (ADRD) cases. Recent findings. Here, we will review the most recent epidemiological, experimental preclinical, and interventional clinical studies examining some of these potentially modifiable risk factors for ADRD. We will focus on new evidence regarding cardiovascular risk factors, air pollution, viral and other infectious agents, traumatic brain injury, and hearing loss. Summary. While greater and higher quality epidemiological and experimental evidence is needed to unequivocally confirm their causal link with ADRD and/or unravel the underlying mechanisms, these modifiable risk factors may represent a window of opportunity to reduce ADRD incidence and prevalence at the population level via health screenings, and education and health policies.
Neuroprotective effect of rice bran enzymatic extract-supplemented diets in a murine model of Parkinsońs disease
(Elsevier, 2024-05-03) Gavilán Dorronzoro, Elena; Flores, Alicia; Castaño Navarro, Angélica; Martín Presas, Luis; Bahatyrevich Kharitonik, Bazhena; Medina Guzmán, Rafael; Parrado Rubio, Juan; Burguillos García, Miguel Ángel; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
Neurodegenerative disorders such as Parkinson's disease, present a global health concern with limited therapeutic options. In this context, dietary interventions have emerged as a potential strategy to counteract the oxidative stress and inflammation underlying these conditions. Rice bran enzymatic extract (RBEE), rich in bioactive compounds, has shown ability in modulating neuroinflammatory responses and improving mitochondrial function. This study investigates the neuroprotective potential of RBEE in a murine model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results reveal that RBEE supplementation effectively preserves the dopaminergic population and reduces MPTP-induced gliosis in the Substantia Nigra (SN). Moreover, RBEE enhances mitochondrial Complex I activity in mouse brains. These findings underscore the potential of RBEE as a dietary supplement to mitigate neuronal loss, neuroinflammation, and mitochondrial dysfunction associated with PD. RBEE is shown as a promising novel candidate in neuroprotective strategies, offering hope in the quest for effective preventive and therapeutic measures in PD.
Inflammatory bowel disease induces pathologicalα-synucleinaggregation in the human gut and brain
(Wiley, 2024-01-16) Espinosa Oliva, Ana María; Ruiz Laza, Rocío; Sarmiento Soto, Manuel; Boza Serrano, Antonio; Rodríguez Pérez, Ana I; Roca Ceballos, María Angustias; García Revilla, Juan; Santiago Pavón, Martiniano; Carvajal Vázquez, Ana Eloísa; Vázquez Carretero, María Dolores; García Miranda, Pablo; Oliva Martin, María José; Machado Quintana, Alberto; Peral Rubio, María José; Herrera Carmona, Antonio José; Venero Recio, José Luis; Martínez de Pablos, Rocío; neuroinflammation; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Ministerio de Economía y Competitividad (MINECO). España; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Ministerio de Sanidad. España; Junta de Andalucía
Aims According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. Methods We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. Results Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD. Conclusion These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.
Isolation and structural determination of cis- and trans-p-coumaroyl-secologanoside (comselogoside) from olive oil waste (alperujo). Photoisomerization with ultraviolet irradiation and antioxidant activities
(Elsevier, 2024-01-30) Bermúdez Oria, Alejandra; Castejón Martínez, María Luisa; Rubio Senent, Fátima; Fernández Prior, África; Rodríguez Gutiérrez, Guillermo; Fernández Bolaños, Juan; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Junta de Andalucía
p-Coumaroyl-6́-secologanoside (comselogoside) is a secoiridoid identified in large amounts in olive fruits, although no studies in vitro or in vivo of comselogoside have been reported. This work focuses on the recovery and purification of this compound from olive mill waste (alperujo). The successive isolation on Amberlite XAD-16 and Sephadex LH-20 resins, allowed a comselogoside extract with 80–85% of purity. A photoisomerization of the vinyl-double bond in the p-coumaroyl moiety occurred when the extract was exposed to ultraviolet radiation and a mixture of the trans and cis-isomers was obtained. Both isomers were characterized using NMR, mass spectroscopy, and UV spectrometry. The J (coupling constant) of the protons on the C7 and C8 on the unsaturated chain were found to be the difference between cis (12.8 Hz) and trans- (15.9 Hz) comselogoside. Cis-isomer exhibited lower radical-scavenging activity than trans, although a synergistic effect occurred when the cis-isomer was supplement by the trans-isomer.
Study of the biochemical activity and plant growth promoting bacteria in soils polluted with oxyfluorfen
(Taylor and Francis Group, 2023-08-13) Navarro Torre, Salvadora; Aguilera Salas, María; Ávila Pozo, Paloma; Parrado Rubio, Juan; Tejada Moral, Manuel; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Microbiología y Parasitología; Universidad de Sevilla. Departamento de Cristalografía, Mineralogía y Química Agrícola; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla. RNM365: Edafologia Ambiental
There is currently a great deal of information available about the toxic effects of oxyfluorfen on soil biochemical activity and microbial biodiversity. However, there is no information about how this herbicide affects plant growth promoting bacteria (PGPB) or their properties, such as biofilm formation, nitrogen fixation, siderophore and auxin production, and phosphate solubilisation. As such in this study an agricultural soil was polluted with the oxyfluorfen herbicide every 30 days at a dose of 4 L ha−1 for a total period of 90 days. During this experimental period, the dehydrogenase activity was determined, a count and isolation of cultivable bacteria was performed, and the PGPB and their properties were characterized. The results indicated that oxyfluorfen inhibits the dehydrogenase activity, with this inhibition increasing with herbicide concentration in the soil (69.9% compared to non-polluted soil). It also causes changes in the population diversity of cultivable bacteria in soils. Regard to the evolution of isolated PGPB, it was found that oxyfluorfen induces the growth of nitrogen-fixing, biofilm-forming, and siderophore-producing bacteria, while negatively affecting the growth of auxin-producing and phosphate-solubilising bacteria. These results suggest that oxyfluorfen modulates the properties of PGPB in a concentration-dependent manner.
Niveles de vitamina D en sangre materna y su relación con el consumo de pescado y los parámetros antropométricos de los recién nacidos en una cohorte de parejas madre/hijos de Sevilla
(Elsevier, 2023-09) Dahiri, Bouchra; Carbonero Aguilar, María del Pilar; Martín Carrasco, Irene; Carrillo, R.; Flórez, N.; Cerrillos, Lucas; Ostos, Rosa; Bautista Palomas, Juan Dionisio; Moreno Navarro, Isabel María; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal; Agencia Estatal de Investigación. España
Introducción Comparar los niveles de vitamina D maternos con la zona de residencia o el consumo de pescado, así como su relación con el peso, la longitud y el perímetro craneal de los bebés. Materiales y métodos Cohorte de 100 parejas madre-hijo (n = 100) de la provincia de Sevilla (Hospital Universitario Virgen del Rocío y Hospital Universitario de Valme). En muestras de sangre materna (edad gestacional ≥ 40 semanas) se han medido los niveles de 25(OH)D mediante quimioluminiscencia. Las medidas antropométricas de los bebés se realizaron mediante métodos estándares. Resultados Con relación a los niveles de vitamina D, 54% presentaban valores deficientes, 26% insuficientes y 20% valores suficientes. Tras un análisis de regresión múltiple, se observa que no hay diferencia significativa entre niveles de vitamina D maternos, la longitud y el perímetro cefálico de los bebés, sin embargo, sí con el peso al nacer (p < 0,05). Al aplicarse la T-Student y el test Wilcoxon, no hay relación entre niveles de vitamina D y el área de residencia ni con el consumo de pescado materno (ambos p > 0,05). Conclusiones El 80% de madres presentan valores deficientes e insuficientes de vitamina D. No hay correlación entre este parámetro y la longitud y perímetro cefálico del bebé, observándose correlación negativa con el peso al nacer. Tampoco se observa correlación entre la zona de residencia o el consumo de pescado y niveles de vitamina D en madres. Sugerimos complementos en dieta de madres gestantes y seguimiento de los niveles de vitamina D en los bebés.
LPS priming before plaque deposition impedes microglial activation and restrains Abeta pathology in the 5xFAD mouse model of Alzheimer's disease.
(Elsevier, 2023-10) Yang, Yiyi; García Cruzado, Marta; Zeng, Hairuo; Camprubi Ferrer, Lluis; Bahatyrevich Kharitonik, Bazhena; Bachiller, Sara; Deierborg, Tomas; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Lund University, Sweden; Swedish Research Council; Swedish Alzheimer Foundation; Olle Engkvist Foundation, Sweden; Swedish Brain Foundation; A.E. Berger Foundation, Sweden; G&J Kock Foundation, Sweden; Royal Physiographic Society of Lund, Sweden; Bertil & Ebon Norlins Foundation, Sweden
Microglia have an innate immunity memory (IIM) with divergent functions in different animal models of neurodegenerative diseases, including Alzheimer’s disease (AD). AD is characterized by chronic neuroinflammation, neurodegeneration, tau tangles and β-amyloid (Aβ) deposition. Systemic inflammation has been implicated in contributing to the progression of AD. Multiple reports have demonstrated unique microglial signatures in AD mouse models and patients. However, the proteomic profiles of microglia modified by IIM have not been well-documented in an AD model. Therefore, in the present study, we investigate whether lipopolysaccharide (LPS)-induced IIM in the pre-clinical stage of AD alters the microglial responses and shapes the neuropathology. We accomplished this by priming 5xFAD and wild-type (WT) mice with an LPS injection at 6 weeks (before the robust development of plaques). 140 days later, we evaluated microglial morphology, activation, the microglial barrier around Aβ, and Aβ deposition in both 5xFAD primed and unprimed mice. Priming induced decreased soma size of microglia and reduced colocalization of PSD95 and Synaptophysin in the retrosplenial cortex. Priming appeared to increase phagocytosis of Aβ, resulting in fewer Thioflavin S+ Aβ fibrils in the dentate gyrus. RIPA-soluble Aβ 40 and 42 were significantly reduced in Primed-5xFAD mice leading to a smaller size of MOAB2+ Aβ plaques in the prefrontal cortex. We also found that Aβ-associated microglia in the Primed-5xFAD mice were less activated and fewer in number. After priming, we also observed improved memory performance in 5xFAD. To further elucidate the molecular mechanism underlying these changes, we performed quantitative proteomic analysis of microglia and bone marrow monocytes. A specific pattern in the microglial proteome was revealed in primed 5xFAD mice. These results suggest that the imprint signatures of primed microglia display a distinctive phenotype and highlight the potential for a beneficial adaption of microglia when intervention occurs in the pre-clinical stage of AD.
Interim report from a 2-year double-blind RCT testing fermented papaya preparation on immune enhancement, endothelial health and QOL in elderly adults
(2023-02-27) Lorenzetti, Aldo; Osato, Maki; He, Fang; Aperio, Cristiana; Ayala Gómez, Antonio; Rasulova, Saida; Barbagallo, Mario; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
profile, and endothelial cell dysfunction. Indeed, increased generation of free radicals as well as immunosenescence are hallmarks of the aging process and age-related diseases. In the past 12 years or so, data has been accumulated on fermented papaya preparation (FPP®)(Osato Research Institute, Gifu, Japan), a specific functional food with robust redox and immune regulator nutrigenomics effect. The aim of this 2-year ongoing study of which we report the first-year data, was to test FPP® in redox, endothelial, and immune markers. Methods: Study population. From a total of 106 subjects, we report the analyzed data referring to 78 clinically stable, healthy, community-dwelling males and females, aged 60 to 75 years. The study was conducted using a double-blind method with designated groups A and B to fulfill the two different treatments. The two treatments are as follows: Group A, also known as “FPP Group,” was given one sachet two times per day containing 4.5g FPP®, along with one placebo capsule provided in the morning. Group B, also known as “AA Group,” was given one papaya-flavored sachet two times per day, along with one antioxidant mixture capsule in the morning. Morning blood samples were collected and tested for: Ultra-sensitive c-reactive protein (a highly sensitive ELISA), inducible nitric oxide synthase (iNOS) (by Human Nitric Oxide Synthase kit), asymmetric dimethylarginine, or ADMA, (a competitive enzyme-linked immunosorbent assay), apoptosis of PBMCs (by Annexin V staining) and MOS 36-item short-form health survey (SF-36) to assess quality of life. Screening and blood tests were carried out as follows: Visit I: Day 0 - Baseline, Visit II: Day 60, or 2 months, Visit III: 6 months, Visit IV: 11 months. Results: Plasma iNOS levels were comparable among both groups at the beginning of the study. FPP®-treated subjects showed a significant increased level at Visits II and III (P<0.05 vs baseline and vs AA). ADMA values were not affected by AA supplementation whereas FPP® treatment was associated with a significant decrease beginning with observation during Visit III (P<0.05 vs baseline and vs AA administration). The FPP® intervention was associated with improvements among several domains of quality of life such as physical function, general health, and mental components (P < 0.01 vs baseline and vs AA group). There was also at significant and comparable positive effect for time on vitality shown in both AA and FPP® groups. Conclusion: Unlike with the antioxidant treatment, the FPP® intervention yielded a transient decrease of ADMA, a decrease of iNOS and lower percentage in apoptotic PBMC. These results suggest that FPP®, by a more multifaceted, subcellular mechanism, as well as non-redox modulatory properties, was beneficially effective in regulating aging markers. These mechanisms are associated with a better SF-36 profile in support of FPP® as a candidate interventional functional food for health maintenance, and specifically in middle-age/elderly subjects.
Galectin-3 is upregulated in frontotemporal dementia patients with subtype specificity
(Wiley, 2023-11) Borrego Écija, Sergi; Pérez Millan, Agnès; Antonell, Anna; Fort Aznar, Laura; Kaya Tilki, Elif; León Halcón, Alberto; Vitorica Ferrández, Francisco Javier; Venero Recio, José Luis; Boza Serrano, Antonio; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Instituto de Salud Carlos III; Generalitat de Catalunya; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
INTRODUCTION Neuroinflammation is a major contributor to the progression of frontotemporal dementia (FTD). Galectin-3 (Gal-3), a microglial activation regulator, holds promise as a therapeutic target and potential biomarker. Our study aimed to investigate Gal-3 levels in patients with FTD and assess its diagnostic potential. METHODS We examined Gal-3 levels in brain, serum, and cerebrospinal fluid (CSF) samples of patients with FTD and controls. Multiple linear regressions between Gal-3 levels and other FTD markers were explored. RESULTS Gal-3 levels were increased significantly in patients with FTD, mainly across brain tissue and CSF, compared to controls. Remarkably, Gal-3 levels were higher in cases with tau pathology than TAR-DNA Binding Protein 43 (TDP-43) pathology. Only MAPT mutation carriers displayed increased Gal-3 levels in CSF samples, which correlated with total tau and 14-3-3. DISCUSSION Our findings underscore the potential of Gal-3 as a diagnostic marker for FTD, particularly in MAPT cases, and highlights the relation of Gal-3 with neuronal injury markers.
Selective accumulation of biotin in arterial chemoreceptors: requirement for carotid body exocytotic dopamine secretion
(2016-12) Ortega Sáenz, Patricia; Macías Gutiérrez, David; Levitsky, Konstantin L.; Rodríguez Gómez, José Antonio; González Rodríguez, Patricia; Bonilla Henao, Victoria; Arias-Mayenco, Ignacio; López Barneo, José; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
Biotin is a water-soluble vitamin required for the function of carboxylases as well asfor the regulation of gene expression. Here, we report that biotin accumulates in unusually largeamounts in cells of arterial chemoreceptors, carotid body (CB) and adrenal medulla (AM). Weshow in a biotin-deficient rat model that the vitamin rapidly disappears from the blood andother tissues (including the AM), while remaining at relatively high levels in the CB. We havealso observed that, in comparison with other peripheral neural tissues, CB cells contain highlevels of SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin.Biotin-deficient rats show a syndrome characterized by marked weight loss, metabolic lacticacidosis, aciduria and accelerated breathing with normal responsiveness to hypoxia. Remarkably,CB cells from biotin-deficient animals have normal electrophysiological and neurochemical (ATPlevels and catecholamine synthesis) properties; however, they exhibit a marked decrease in the sizeof quantal catecholaminergic secretory events, which is not seen in AM cells. A similar differentialsecretory dysfunction is observed in CB cells treated with tetrabenazine, a selective inhibitor ofthe vesicular monoamine transporter 2 (VMAT2). VMAT2 is highly expressed in glomus cells (incomparison with VMAT1), and in biotin-deficient animals VMAT2 protein expression decreases in parallel with the decrease of biotin accumulated in CB cells. These data suggest that biotinhas an essential role in the homeostasis of dopaminergic transmission modulating the transportand/or storage of transmitters within small secretory granules in glomus cells.
FarmaEscape El Retorno: el empleo de una Escape Room como herramienta de aprendizaje en los estudios de la Facultad de Farmacia de la Universidad de Sevilla
(Real e Ilustre Colegio Oficial de Farmacéuticos, 2023) Ríos-Reina, Rocío; Callejón Fernández, Rocío; Durán Lobato, María Matilde; García Miranda, Pablo; Gutiérrez-Praena, Daniel; Martín Bueno, Julia; Ruiz de la Haba, Rafael; Ruiz Laza, Rocío; Sánchez Hidalgo, Marina; Talero Barrientos, Elena Mª; Sarmiento Soto, Manuel; Zurita Carrasco, Antonio; Callejón Fernández, Raquel María; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal; Universidad de Sevilla. Departamento de Microbiología y Parasitología; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Fisiología; Universidad de Sevilla. Departamento de Química Analítica; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla
Una Escape Room es un juego de escapismo en el que un grupo de personas están “atrapadas” en una sala cerrada, debiendo resolver una serie de enigmas o pruebas para conseguir “escapar” en un tiempo menor del estipulado. En el ámbito educativo, el uso de Escape Rooms es un recurso de reciente implantación, usándose cada vez más frecuentemente para incentivar la colaboración entre alumnos y el trabajo en equipo, y poner a prueba las habilidades adquiridas durante la etapa educativa. Además, esta actividad contribuye a desarrollar habilidades sociales, gestionar el tiempo y consolidar los conocimientos adquiridos de un modo atrayente para el alumnado. En este trabajo se expone el desarrollo de una Escape Room multidisciplinar para alumnos del Grado en Farmacia y del Doble Grado en Farmacia y en Óptica y Optometría de la Universidad de Sevilla, con el fin de cimentar el aprendizaje de los estudiantes de los últimos cursos de estos estudios, introduciéndoles al futuro profesional. El profesorado participante en este proyecto de innovación docente estuvo constituido por 13 profesores adscritos a siete Departamentos de la Facultad de Farmacia. En la actividad, de carácter voluntario, se inscribieron 75 alumnos de ambos Grados, dando lugar a un total de 15 grupos. Durante la actividad, se desarrollaron pruebas como la determinación de almidón en alimentos, traducción de ADN, realización e interpretación de ensayos analíticos, uso del microscopio óptico, medida de pH y selección de medicamentos. Los resultados obtenidos de participación y encuestas posteriores realizadas al alumnado pusieron de relevancia el interés y la motivación generados por la actividad, así como el fortalecimiento del conocimiento adquirido de las distintas áreas. La actividad obtuvo puntuaciones máximas en originalidad y organización (91,1% de los encuestados), contribución al trabajo en equipo (94.6%) y fue recomendada por la totalidad de los participantes que la realizaron.
Betalain profile, phenolic content, and color characterization of different parts and varieties of opuntia ficus-indica
(American Chemical Society, 2014-08-20) Cejudo Bastante, María Jesús; Chaalal, Makhlouf; Louaileche, Hayette; Parrado Rubio, Juan; Heredia Mira, Francisco José; Universidad de Sevilla. Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
Three different varieties of Opuntia ficus-indica (R, red; Y, yellow; RY, red-yellow) have been considered in this study. Attention was focused on differential tristimulus colorimetry and on the analysis of individual betalains (HPLC-DAD-ESI-ToF-MS) and phenolic content, scarcely previously reported in these kinds of samples. The importance of this research stems from the elucidation of the parts and varieties of cactus pear more optimal for use as natural colorants and sources of phenolics and betalains. Thus, the RY pulp was appropriate to obtain colorants with high color intensity (Cab = 66.5), whereas the whole Y fruit and R pulp reached powerful and stable yellow and red colors, respectively (Cab/hab, 57.1/84.7 and 61.1°/81.8°). This choice was also based on the visually appreciable differences (ΔEab > 5) among samples, mainly quantitative (%Δ2L, %Δ2C). In addition, seeds of all Opuntia varieties showed significantly (p < 0.05) similar phenolic content (around 23.3 mg/g) and color characteristics.
Enzymatic Preparation of Mushroom By-product Protein Hydrolysates (Mb-PPHs)
(Springer, 2023-08-14) Inca Torres, Alberto Renato; Aguilera Velázquez, José Raúl; Urbina Salazar, Anabell del Rocío; Carbonero Aguilar, María del Pilar; Moreno Navarro, Isabel María; Bautista Palomas, Juan Dionisio; Root growth; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE); Universidad de Sevilla
The excessive use of chemical fertilizers can cause severe environmental damage. In recent decades, the application of biostimulants to improve soil composition and stimulate plant growth has contributed significantly to environmental preservation. In this paper, we studied the production and characterization of an amino acid/peptide-enriched biostimulant using edible mushroom (Agaricus bisporus) by-products (tails and nonmarketable mushrooms) as raw materials and commercial proteases as hydrolytic agents. A single hydrolytic process using four different endoproteases, Alcalase®, L-450, Flavourzyme® or papain, and a sequential hydrolytic process using two proteases, an endoprotease and an exoprotease, Alcalase® + Flavourzyme® or L-450 + Flavourzyme), were conducted. A preevaluation of potential plant biostimulants was also carried out, testing the biostimulant capacity of single and sequential Mb-PPHs to stimulate maize seed germination and root growth, as well as the evaluation of the vigor index (VI), with very promising results.
Diseño y perspectiva longitudinal de un proyecto de biotecnología farmacéutica basado en la economía circular
(Real e Ilustre Colegio Oficial de Farmacéuticos, 2023-07) Manfredi Lozano, María; Sarmiento Soto, Manuel; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
Dentro de la asignatura de “Biotecnología Farmacéutica” del grado de Farmacia de la Universidad de Sevilla, sus competencias específicas intentan promover entre el alumnado un pensamiento científico en pos de la generación de ideas que afronten los actuales problemas de renidmiento existentes en el tejido productivo global, así como de estrategias que promuevan nuevos procesos de reutilización de recursos en el campo de la biotecnología. En este sentido, debido a la pluralidad de los departamentos implicados actualmente en la asignatura, nuestro proyecto pretende integrar una serie de competencias multidisciplinares promoviendo la creación de un proyecto novedoso que responda a los problemas relacionados con el cambio climático y la degradación del medio ambiente, tal y como se contempla en el Pacto Verde Europeo 2020. Con los conocimientos adquiridos durante la asignatura, los alumnos deberán diseñar una idea patentable, con potencial para convertirse en una Spin-Off integrada dentro de la Universidad de Sevilla. La creación de empresas de base tecnológica dentro de las universidades, también llamadas Start-Up o Spin-Off universitarias, ha probado ser en los últimos años uno de los mecanismos más eficaces de transferencia de resultados de investigación y tecnología desde los centros de investigación universitarios al sector productivo. Este tipo de proyectos son especialmente relevantes en al ámbito de la innovación, generación de empleo de calidad, la inserción de jóvenes emprendedores al mercado laboral y, por tanto, su aportación al desarrollo socioeconómico. Además de promover el uso práctico de los conocimientos adquiridos durante el grado, desde el profesorado se generarán contactos con empresas del sector, con base en Andalucía, para organizar visitas guiadas a sus instalaciones y posibilitar la realización de prácticas por parte de los estudiantes y así intentar cimentar los primeros contactos entre alumnos de 3º de Farmacia y el mercado laboral.

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