Artículos (Bioquímica y Biología Molecular)

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

Examinar

Mostrando 1 - 20 de 268

Melatonin controls experimental autoimmune encephalomyelitis by altering the T effector/regulatory balance
(Elsevier, 2015-06-26) Álvarez Sánchez, Nuria; Cruz Chamorro, Iván; López González, Antonio; Utrilla Alcolea, José Carmelo; Fernández-Santos, José María; Martínez López, Alicia; Lardone, Patricia Judith; Guerrero Montávez, Juan Miguel; Carrillo Vico, Antonio; Bioquímica Médica y Biología Molecular e Inmunología; Citología e Histología Normal y Patológica; Bioquímica y Biología Molecular; Instituto de Salud Carlos III; Gobierno de España; Junta de Andalucía; CTS439: Sistema Neuroendocrino Difuso; CTS160: NeuroInmunoEndocrinología Molecular
Experimental autoimmune encephalomyelitis (EAE), the experimental model for multiple sclerosis (MS), is triggered by myelin-specific Th1 and Th17 cells. The immunomodulatory activities of melatonin have been shown to be beneficial under several conditions in which the immune system is exacerbated. Here, we sought to elucidate the basis of the melatonin protective effect on EAE by characterizing the T effector/regulatory responses, particularly those of the memory cell subsets. Melatonin was tested for its effect on Th1, Th17 and T regulatory (Treg) cells in the lymph nodes and CNS of immunodominant peptide of myelin oligodendrocyte glycoprotein (pMOG)-immunized and EAE mice, respectively. The capacity of melatonin to ameliorate EAE as well as modifying both T cell response and effector/regulatory balance was surveyed. T cell memory subsets and CD44, a key activation marker involved in the EAE pathogenesis, were also examined. Melatonin protected from EAE by decreasing peripheral and central Th1/Th17 responses and enhancing both the Treg frequency and IL-10 synthesis in the CNS. Melatonin reduced the T effector memory population and its pro-inflammatory response and regulated CD44 expression, which was decreased in T effector cells and increased in Tregs. The alterations in the T cell subpopulations were associated with a reduced mononuclear infiltration (CD4 and CD11b cells) of the melatonin-treated mice CNS. For the first time, we report that melatonin protects against EAE by controlling peripheral and central T effector/regulatory responses, effects that might be partially mediated by CD44. This immunomodulatory effect on EAE suggests that melatonin may represent an effective treatment option for MS.
Galectin-3 shapes microglial phenotype through endogenous and exogenous mechanisms
(Frontiers Media S.A., 2025-12-18) Camprubí-Ferrer, Lluis; Yang, Yiyi; Fernández-Calle, Rosalía; Boza Serrano, Antonio; García Revilla, Juan; Frontiñán-Rubio, Javier; Deierborg, Tomas; Bioquímica y Biología Molecular
Galectin-3 (Gal3) is a multifunctional lectin expressed and released by microglia, where it influences diverse processes in both homeostasis and disease. To dissect its intracellular and extracellular roles, we generated Gal3-deficient BV2 microglial cells and systematically assessed how genetic deletion and exogenously added recombinant Gal3 shape microglial physiology. Gal3 deletion increased cell area, mitochondrial activity, and motility without affecting proliferation, linking endogenous Gal3 to microglial energetic control and dynamic cellular physiology. Endogenous Gal3 was required to maintain CD11b surface levels, and restrains TREM2 and Clec7a expression, whereas exogenous Gal3 promoted CD45 internalization and drove a paracrine TNFα release. Endogenous and exogenous Gal3 are synergistically needed for Syk phosphorylation and NOX2 expression. Internalization assays demonstrated that endogenous Gal3 constrained phagocytosis and endocytosis, while exogenous Gal3 enhanced endocytosis in a paracrine manner. In the Alzheimer’s disease 5xFAD mouse model, where Gal3 deletion was reported to lower amyloid plaque burden, the absence of Gal3 does not affect microgliosis but elevates Clec7a levels around plaques. Together, these findings reveal Gal3 as a critical regulator of microglial homeostasis, uptake pathways, receptor expression, and inflammatory signaling. We have defined a novel microglial regulation based on endogenous and exogenous pools of Gal3. By identifying a novel Gal3-Clec7a interaction, this work highlights Gal3 as a key modulator of microglial phenotype and a potential target for therapeutic modulation of neuroinflammation.
Galectin 3: A new player in the pathogenesis of Parkinson's disease
(Walters Kluwer, 2026) García Revilla, Juan; Venero Recio, José Luis; Rodríguez Gómez, José Antonio; Bioquímica y Biología Molecular; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España
Co-application of salicylic acid and potassium induce salinity tolerance by modulating ion homeostasis, chlorophyll pigments and photosynthetic apparatus in wheat
(Springer, 2025-11-12) Shaheen, Farzana; Ashraf, Muhammad Yasin; Hussain, Muhammad Iftikhar; Khan, Zafar Iqbal; Chaudhry, Usman Khalid; Abideen, Zainul; Parrado Rubio, Juan; Rahman, Muhammad Habib Ur; El-Keblawy, Ali; Bioquímica y Biología Molecular
Salinity is a major abiotic stress limiting global agricultural productivity, particularly affecting the physiological functions, nutrient uptake, and gas exchange processes of crops like wheat (Triticum aestivum L.). As salinization of arable land continues to expand, identifying effective and sustainable mitigation strategies is critical. This study evaluated the impact of foliar-applied salicylic acid (SA) (0, 0.01, 0.02, and 0.03%) and potassium (K) (0, 0.05, 0.1, and 0.15%) at two key growth stages (vegetative and grain filling) on two wheat varieties (WL-711 and Kohistan-97) grown under saline (120 mM NaCl; ≈12 dS/m) and non-saline conditions in a controlled pot experiment. Results showed that foliar application of SA (0.02%) and K (0.1%) significantly improved leaf nutrient concentrations (N, P, K, Ca, and Mg) and enhanced photosynthetic pigments (chlorophyll a, b, total chlorophyll, and carotenoids) under salt stress. These treatments also alleviated the adverse effects of salinity on gas exchange parameters, with WL-711 displaying higher tolerance than Kohistan-97. Overall, exogenous application of SA and K effectively improved physiological resilience and nutrient homeostasis in salt-stressed wheat. Notably, this study demonstrates, for the first time, the synergistic effect of optimal foliar doses of SA and K at two critical developmental stages, offering a practical and low-cost strategy to mitigate salinity stress in wheat. The findings provides a valuable basis for future field-scale interventions to enhance wheat productivity in salt-affected regions.
Tissue‐specific early and late activated lymphocytes immunophenotype in chronic rhinosinusitis with nasal polyps
(Wiley, 2024-01-24) López Enríquez, Soledad; Porras González, Cristina; Moreno‐Luna, Ramón; Palomares Jerez, María Francisca; Muñoz‐Bravo, José Luis; Alba Jiménez, Gonzalo; Santa-María Pérez, Consuelo; Maza Solano, Juan Manuel; Martín‐Jiménez, Daniel Iván; Pérez Pérez, Antonio; Moreno‐Luna, Rafael; Sánchez Margalet, Víctor; Sánchez Gómez, Serafín; Bioquímica Médica y Biología Molecular e Inmunología; Bioquímica y Biología Molecular; Cirugía; Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España
Key points T-cell activation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is enriched by late cytotoxic T cells. The proportion of early and intermediate activated cytotoxic T cells decreases in nasal polyps of patients with CRSwNP. Our results identify late activated cytotoxic T cells as potential biomarkers or therapeutic targets for patients with CRSwNP.
Design of Fermentative Technology for the Valorization of Pig Bristle Keratins into Biostimulant for Agricultural Applications
(American Chemical Society (ACS), 2025-09-16) Orts, Ángel; López, Jesús; Orts Gómez, José María; Navarro Torre, Salvadora; Naranjo Fernández, Emilia; Caballero Jiménez, Pablo; Martín Presas, Luís; Castaño Navarro, Angélica; Parrado Rubio, Juan; Bioquímica y Biología Molecular; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
The elimination of keratin-derived waste, such as pig bristles, represents a significant challenge due to its high production levels and resistance to degradation. However, the keratinous composition also makes pig bristles a valuable waste material with significant potential for bioconversion into biostimulants rich in bioavailable nitrogen, peptides, and amino acids. To achieve degradation, microorganisms with keratinolytic activity isolated from the raw material were selected. Based on the best performance in plant PGP traits, solubility, and protease activity, Sporosarcina luteola was chosen to implement a fermentation technology that converts pig bristle waste. The fermented product comprises three classes of biostimulant components: the biomass of S. luteola, the enzymatic secretions of this microorganism, and the hydrolyzed organic matter from pig bristles, which is rich in protein hydrolysates and free amino acids. The biostimulant was evaluated in soil at the biochemical level (enzymatic activities) and in plants under oxidative stress, demonstrating a positive effect. These findings highlight the fermentation process using S. luteola as a promising strategy for the comprehensive valorization of pig bristle waste, resulting in products with significant agronomic and environmental benefits.
Effect of soil temperature and moisture on degradation of the oxyfluorfen herbicide
(Taylor & Francis, 2025-08-12) Paneque Macías, Patricia Isabel; Gómez Parrales, Isidoro Ángel; Parrado Rubio, Juan; Orts Gómez, José María; Tejada Moral, Manuel; Cristalografía, Mineralogía y Química Agrícola; Bioquímica y Biología Molecular; Ministerio de Ciencia e Innovación (MICIN). España
We have studied the combined effect of temperature and moisture on a soil contaminated with the oxyfluorfen herbicide at a dose of 4 l ha−1 in terms of the biochemical activity (dehydrogenase activity and ergosterol content) of said soil, as well as on the concentration of said herbicide over a 90-day period in a laboratory setting. Two degrees of moisture were used: (1) irrigated soils maintained at 60% of their water retention capacity and (2) non-irrigated soils (non-watered soils, without irrigation). These treatments were subjected to three temperatures (4 °C, 25 °C, and 40 °C, respectively). In all cases, the oxyfluorfen caused a toxic effect on both the dehydrogenase activity and ergosterol content of the soil. However, this toxic effect was greater in non-watered soils, possibly due to the combined effect of the herbicide toxicity and the soil drought conditions. With regard to temperature, the results indicate that dehydrogenase activity and ergosterol content in soil were more negatively affected when samples were incubated at higher temperatures (40 °C). Statistical analysis suggests that temperature may have a greater specific weight or influence than soil moisture, since a variation in temperature causes a variation in soil moisture.
Effective Validation of Primary Care Patient Triage Classification Via Tele-Ophthalmology With Optometrist Support
(SAGE Publications, 2025-08-27) Carrasco Solís, Rafael; Rodríguez Griñolo, María Rosario; Ponte Zúñiga, Beatriz; Mataix Albert, Beatriz; González Troncoso, María José; Martínez de Pablos, Rocío; Rodríguez de la Rúa Franch, Enrique; Bioquímica y Biología Molecular; Cirugía; Instituto de Salud Carlos III
The triage classification and diagnosis of eye diseases in primary care patients through teleophthalmology were performed by ophthalmologists, optometrists, and family physicians. The agreement in triage classification and diagnosis between observers, as well as the quality of referrals from primary care to ophthalmology, were evaluated. Study to compare methods using a non-inferiority method approach. The sample comprised 220 patients with suspected ocular problems evaluated by family physicians. These patients were examined by an optometrist (observer 1) using a Visionix VX650 multi-diagnostic platform. The optometrist provided a suspected diagnosis and a referral. The tests were forwarded electronically to an ophthalmologist (observer 2), who provided a diagnosis and referral. Subsequently, they were reviewed in person by an ophthalmologist (observer 3) who provided a diagnosis and referral. The observers worked independently and at different times, without knowledge of each other’s evaluations, ensuring the objectivity of the analysis. We analyzed interobserver agreement in triage referrals and diagnosis using the Kappa index. The triage classification of patients by teleophthalmology coincides with that of in-person ophthalmology in 91.2% of the cases (Kappa = 0.819). The optician’s triage classification coincided with in-person ophthalmology in 91.3% (Kappa = 0.858) and with teleophthalmology in 92.3% (Kappa = 0.851). The diagnostic categories, teleophthalmology and in-person ophthalmology coincided in 84.61% of the cases (Kappa = 0.80). The optician coincided with in-person ophthalmology in 90.65% (Kappa = 0.88) and with teleophthalmology in 90.9% of the diagnoses (Kappa = 0.87). There was a very high level interobserver agreement for both triage classification and diagnostic categories. This validates our teleophthalmology approach, conducted in a primary care setting by optometrists, family physicians, and ophthalmologists, for an effective triage classification of patients referred to ophthalmology services. This telemedicine also accurately categorizes patients based on their conditions, optimizing resources, reducing waiting times and waiting lists.
Inactivation of the PHD3-FOXO3 axis blunts the type I interferon response in microglia and ameliorates Alzheimer’s disease progression
(American Association for the Advancement of Science (AAAS), 2025-05-28) Sánchez-García, Manuel A.; Cabello Rivera, Daniel; Romero Molina, Carmen; Navarro Garrido, Victoria; López Barneo, José; Vizuete Chacón, María Luisa; Muñoz Cabello, Ana María; Rosales Nieves, Alicia E.; Pascual, Alberto; Bioquímica y Biología Molecular; Fisiología Médica y Biofísica; Agencia Estatal de Investigación. España; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE); Cancer Research. United Kingdom; Junta de Andalucía; Medical Research Council. United Kingdom; Universidad de Sevilla; Wellcome Trust. United Kingdom
Microglia respond to Alzheimer’s disease (AD) with varied transcriptional responses. We show that oligomeric Aß (oAß) induces the expression of Hif1a and Egln3 in microglia in vitro, together with the transcription of the type I interferon signature (IFNS) genes in a PHD3-dependent manner. We identify FOXO3 as a repressor of IFNS, whose abundance decreases upon PHD3 induction in response to oAß. In vivo, loss of PHD3 correlates with abrogation of the IFNS and activation of the disease-associated microglia signature, an increase in microglia proximity to Aß plaques and phagocytosis of both Aß and small plaques. PHD3 deficiency mitigated the Aß plaque–associated neuropathology and rescued behavioral deficits of an AD mouse model. Last, we demonstrate that microglial PHD3 overexpression in the absence of Aß pathology is sufficient to induce the IFNS and behavioral alterations. Together, our data strongly indicate that the inactivation of the PHD3-FOXO3 axis controls the microglial IFNS in a cell autonomous manner, improving AD outcome.
Distinct and redundant roles of the Arabidopsis OCTOPUS gene family in plant growth beyond phloem development
(Oxford University Press, 2025-01-11) Crivelli, Simona; Bartusch, Kai; Ruiz Sola, M. Águila; Coiro, Mario; Schmidt Kjolner Hansen, Signe; Truernit, Elisabeth; Bioquímica y Biología Molecular
The Arabidopsis root apical meristem is an excellent model for studying plant organ growth. This involves a coordinated process of cell division, elongation, and differentiation, with each tissue type developing according to its own schedule. Among these tissues, the protophloem is particularly important, differentiating early to supply nutrients and signalling molecules to the growing root tip. The OCTOPUS (OPS) protein and its homologue OPS-LIKE 2 (OPL2) are essential for proper root protophloem differentiation and, probably through this role, indirectly promote root growth. Here, we explored the roles of the other three OPS homologues in Arabidopsis, OPL1, OPL3, and OPL4. OPS/OPL genes exhibited overlapping expression patterns and functions, with a high degree of redundancy among them. Although higher order mutants did not display more severe phloem defects, they exhibited significantly reduced root growth compared with the ops opl2 mutant. These results indicate a direct contribution of the investigated OPL genes to meristematic activity. While our focus was on root growth, the OPS/OPL gene family also plays a positive role in regulating shoot growth, emphasizing its broader impact on plant development. Furthermore, our analyses reiterate the central role of OPS and the phloem domain in controlling overall plant growth.
The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration
(Oxford University Press, 2025-02-25) Öztürk, Muhammet M.; Emgård, Jakob; García Revilla, Juan; Fernández-Calle, Rosalía; Yang, Yiyi; Deierborg, Tomas; Roos, Tomas T.; Bioquímica y Biología Molecular
Numerous neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis share a neuropathological hallmark: aberrant protein aggregation in the CNS. Microglia, the brain’s innate immune cells, also play a pivotal role in the pathogenesis of these disorders. Multiple studies indicate that these pathological aggregates can propagate throughout the brain in a prion-like manner. A protein/peptide that adopts a prion-like conformation can induce homologous proteins to misfold into a prion-like conformation through templated seeding, enabling cell-to-cell spread and accelerating protein aggregation throughout the brain. Two important questions in the prion-like paradigm are where the prion-like misfolding occurs and how the prion-like aggregates are spread throughout the CNS. Here, we review the role of microglia and associated inflammation in the prion-like spread of pathologically aggregated proteins/peptides in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. A growing body of evidence suggests that microglia can internalize prion-like proteins and transport them to neighbouring neurons and other glial cells. Microglia may also influence the potential seeding of proteins in neurons and induce inflammatory pathways in their microenvironment. This review aims to broaden the understanding of the role of microglia in the prion-like spread of protein aggregation.
Intergenerational Influence of Paternal Obesity on Metabolic and Reproductive Health Parameters of the Offspring: Male-Preferential Impact and Involvement of Kiss1-Mediated Pathways
(Oxford University Press, 2018-02) Sanchez-Garrido, M. A.; Ruiz-Pino, F.; Velasco, I.; Barroso, A.; Fernandois, D.; Manfredi Lozano, María; Tena-Sempere, M.; Bioquímica y Biología Molecular; Ministerio de Economía y Competitividad (MINECO). España; Ministerio de Sanidad. España; Junta de Andalucía; European Commission (EC)
Obesity and its comorbidities are reaching epidemic proportions worldwide. Maternal obesity is known to predispose the offspring to metabolic disorders, independently of genetic inheritance. This intergenerational transmission has also been suggested for paternal obesity, with a potential negative impact on the metabolic and, eventually, reproductive health of the offspring, likely via epigenetic changes in spermatozoa. However, the neuroendocrine component of such phenomenon and whether paternal obesity sensitizes the offspring to the disturbances induced by high-fat diet (HFD) remain poorly defined. We report in this work the metabolic and reproductive impact of HFD in the offspring from obese fathers, with attention to potential sex differences and alterations of hypothalamic Kiss1 system. Lean and obese male rats were mated with lean virgin female rats; male and female offspring were fed HFD from weaning onward and analyzed at adulthood. The increases in body weight and leptin levels, but not glucose intolerance, induced by HFD were significantly augmented in the male, but not female, offspring from obese fathers. Paternal obesity caused a decrease in luteinizing hormone (LH) levels and exacerbated the drop in circulating testosterone and gene expression of its key biosynthetic enzymes caused by HFD in the male offspring. LH responses to central kisspeptin-10 administration were also suppressed in HFD males from obese fathers. In contrast, paternal obesity did not significantly alter gonadotropin levels in the female offspring fed HFD, although these females displayed reduced LH responses to kisspeptin10. Our findings suggest that HFD-induced metabolic and reproductive disturbances are exacerbated by paternal obesity preferentially in males, whereas kisspeptin effects are affected in both sexes.
ETS transcription factor pointed controls germline survival in Drosophila
(PLOS, 2025-08-25) Rosales Nieves, Alicia E.; Marín-Menguiano, M.; López-Onieva, L.; Garrido-Maraver, J.; González-Reyes, A.; Bioquímica y Biología Molecular; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Junta de Andalucía
Proper gonad development is a pre-requisite for gametogenesis and reproduction. During female gonad formation in Drosophila, the EGF receptor (EGFR) signalling pathway ensures the correct number of primordial germ cells (PGCs) populate the larval gonad. We study the gene pointed (pnt), which acts downstream of the EGFR receptor and belongs to the ETS transcription factor family, with a previously unknown function in gonadogenesis. We report that pnt is expressed in female larval gonads and later in the adult ovarian germline niche and that it is required to sustain proper gametogenesis. Loss of pnt function in female larval gonads, similar to the EGFR, induced PGC overproliferation. Conversely, we isolated a novel mutant allele gene, termed pntaga, which resulted in agametic gonads and ovaries. While pntaga embryos developed gonads containing a normal complement of PGCs, these are subsequently lost by apoptosis during late larval and pupal stages. Molecular characterization of pntaga revealed reduced expression levels of the different pnt isoforms, unveiling a complex autoregulatory network involving the three Pnt proteins. We propose that germline survival in Drosophila gonads requires a precise tuning of EGFR signalling to ensure the appropriate transcriptional activation of its target pnt.
Amyloid structural changes studied by infrared microspectroscopy in bigenic cellular models of alzheimer’s disease
(MDPI, 2021-03-26) Paulus, Agnes; Engdahl, Anders; Yang, Yiyi; Boza Serrano, Antonio; Bachiller, Sara; Torres-Garcia, Laura; Klementieva, Oxana; Bioquímica y Biología Molecular; Bioquímica Médica y Biología Molecular e Inmunología; BIO113: Mecanismos de Muerte Celular en Enfermedades Neurodegenerativas
Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging nature of characterizing the secondary structure of amyloids in cells. To overcome this and investigate the molecular changes in proteins directly in cells, we used synchrotron-based infrared microspectroscopy, a label-free and non-destructive technique available for in situ molecular imaging, to detect structural changes in proteins and lipids. Specifically, we evaluated the formation of β-sheet structures in different monogenic and bigenic cellular models of Alzheimer’s disease that we generated for this study. We report on the possibility to discern different amyloid signatures directly in cells using infrared microspectroscopy and demonstrate that bigenic (amyloid-β, α-synuclein) and (amyloid-β, Tau) neuron-like cells display changes in β-sheet load. Altogether, our findings support the notion that different molecular mechanisms of amyloid aggregation, as opposed to a common mechanism, are triggered by the specific cellular environment and, therefore, that various mechanisms lead to the development of Alzheimer’s disease.
An Insertion Within SIRPbeta1 Shows a Dual Effect Over Alzheimer's Disease Cognitive Decline Altering the Microglial Response
(IOS Press BV, 2024-03) García-Alberca, José María; de Rojas, Itziar; Sánchez-Mejías, Elisabeth; Garrido-Martín, Diego; González-Palma, Laura; Jiménez, Sebastián; Muñoz Castro, Clara; Navarro Garrido, Victoria; Mir Rivera, Pablo; Vitorica Ferrández, Francisco Javier; GERALD consortium; Bioquímica y Biología Molecular; Medicina; Ministerio de Ciencia e Innovación (MICIN). España; Instituto de Salud Carlos III; Junta de Andalucía
Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPβ1, a surface receptor that triggers amyloid-β(Aβ) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPβ1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPβ1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPβ1 protein isoform landscape compromising its ability to bind oligomeric Aβ and its affinity for TYROBP. SIRPβ1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aβ ratio (p=0.018) and a higher risk to develop AD (OR=1.678, p=0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p<0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p=0.013). Transcriptional analysis also shows that the SIRPβ1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPβ1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aβ. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPβ1 structural variant might be considered as a potential modulator of this causative pathway.
Changes in neurotransmitter levels associated with the deficiency of some essential amino-acids in the diet
(Cambridge University Press, 1992) Herrera Carmona, Antonio José; Venero Recio, José Luis; Machado, Alberto; Cano, Josefina; Bioquímica y Biología Molecular
The contents of dopamine (DA) and serotonin (5-HT) and their metabolites were measured in rat substantia nigra and corpus striatum following dietary changes, including restriction of protein content (low-protein diet; LPD) and the contents of several large neutral amino acids (isoleucine, leucine, methionine, phenylalanine, tryptophan and valine) for 25 d. The LPD produced an increase in the concentration of tyrosine (TYR) in the two regions of the brain studied. This effect was also observed with all amino acid deficiencies studied except for valine in the substantia nigra, tryptophan in the striatum and phenylalanine in both regions. Likewise, the concentration of 5-hydroxyindolacetic acid (5-HIAA), the main metabolite of 5-HT, increased in the substantia nigra but not in the striatum after LPD, as well as with all the amino acid deficiencies studied, with the exception of tryptophan deficiency. In this case there was a dramatic effect on all components of the serotoninergic system, with decreases in the concentration of tryptophan (TRP; precursor), 5-HT and 5-HIAA. This behaviour clearly shows an interrelationship between precursor (TRP) availability and 5-HT synthesis and metabolism. With valine deficiency, dopaminergic and serotoninergic systems demonstrated opposite effects in the substantia nigra and the corpus striatum, and the behaviour of the two monoamines was also opposite within each structure. The significance of these changes is discussed.
Polyurethane wastes conversion into a plant biostimulant via ozonolytic attack: An innovative strategy for waste management and sustainable agriculture
(Elsevier, 2025-06-07) Orts Gómez, José María; Orts Gómez, Ángel; Naranjo Fernández, Emilia; Castaño Navarro, Angélica; Tejada Moral, Manuel; Gómez Parrales, Isidoro Ángel; Parrado Rubio, Juan; Bioquímica y Biología Molecular; Cristalografía, Mineralogía y Química Agrícola; Ministerio de Ciencia e Innovación (MICIN). España; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; European Union (UE)
A novel, non-toxic plant biostimulant has been developed through the depolymerization of polyurethane (PU) foams via an aqueous ozonolysis process. This method yields a water-based extract rich in small, soluble molecules, referred to as oxidized liquid extract (OLE), which acts as a growth-promoting substrate for pepper plants (Capsicum annuum). This approach not only enables the conversion of PU waste into plant biomass but also represents an innovative model for circular economy implementation. When applied at low concentrations (diluted 1:5 and 1:10), OLE elicits a hormetic response, enhancing photosynthetic performance, protein content, and photosynthetic pigment levels. Additionally, it stimulates the accumulation of industrially relevant secondary metabolites such as terpenoids and capsaicinoids an effect likely linked to the extract’s high nitrate content. Although short-chain polyols were detected in the fruits of plants treated with the 1:5 dilution, these compounds are biodegradable and widely used in pharmaceutical and cosmetic applications. Moreover, OLE induces favorable shifts in rhizospheric microbial communities, promoting the enrichment of biofertilizing bacterial genera capable of transforming extract derived compounds and enhancing the adsorption of biomolecules secreted by plant roots. This sequential chemical and biological transformation facilitates the complete valorization of a highly recalcitrant polymeric waste, resulting in a bioactive extract that supports plant growth and development. Taken together, this strategy offers a promising and sustainable solution that integrates waste management with agricultural productivity, aligning with the core principles of the circular bioeconomy.
Drug screening targeting TREM2-TYROBP transmembrane binding
(Springer Nature, 2025-05-05) Cobas-Carreño M.; Esteban-Martos A.; Tomas-Gallardo L.; Iribarren I.; González-Palma L.; Rivera Ramos, Alberto; Elena-Guerra, J.; Alarcón-Martín, E.; Ruiz Laza, Rocío; Bravo, M.J.; Venero Recio, José Luis; Morató, X.; Bioquímica y Biología Molecular
TREM2 encodes a microglial membrane receptor involved in the disease-associated microglia (DAM) phenotype whose activation requires the transmembrane interaction with TYROBP. Mutations in TREM2 represent a high-impact risk factor for Alzheimer’s disease (AD) which turned TREM2 into a significant drug target. We present a bacterial two-hybrid (B2H) system designed for high-throughput screening of modulators for the TREM2-TYROBP transmembrane interaction. In a pilot study, 315 FDA-approved drugs were analyzed to identify potential binding modifiers. Our pipeline includes multiple filtering steps to ensure candidate specificity. The screening suggested two potential candidates that were finally assayed in the human microglial cell line HMC3. Upon stimulation with anti-TREM2 mAb, pSYK/SYK ratios were calculated in the presence of the candidates. As a result, we found that varenicline, a smoking cessation medication, can be considered as a transmembrane agonist of the TREM2-TYROBP interaction.
Insight into the chemical and nutritional fat profile of Tenebrio molitor larvae reared on different Agri-food by-products
(Elsevier, 2025) Morales Gómez, María Lourdes; Segura Borrego, María del Pilar; Aguilera-Velázquez, José Raúl; Callejón Fernández, Raquel María; Gutiérrez-Praena, Daniel; Úbeda Aguilera, Cristina; Nutrición y Bromatología, Toxicología y Medicina Legal; Bioquímica y Biología Molecular; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Agencia Estatal de Investigación. España; European Union (UE)
Insects are capable of feeding with a variety of substrates, being possible obtaining products rich in protein using by-products from agri-food industry. Hence, the aim of this work was evaluating the effect of different diets based on three agri-food industry by-products of Tenebrio molitor larvae’s total fat contents and fatty acid profiles. Stabilized Alperujo (ALP), Pleorotus ostreatus spent substrate (POS) and olive leaf flour (OLF) were used mixed with wheat bran, control diet, at different percentages (20–100 %). All substrates studied modified the parameter analysed respect to the control diet. OLF subtract led to the greatest effects on the total fat content at percentage higher than 40 %. Respect to fatty acid profile, the most relevant changes were the increases of total MUFA content in samples from all T. molitor larvae fed with ALP and in most of those fed with POS, due to the specific increases of oleic acid content. On the contrary, total PUFA content decreased in most cases except for OLF substrate when the addition percentages were lower than 100 %. Moreover, OLF substrate enhanced the presence of ω-3. Finally, according to European regulations on nutritional claims, this fat fraction could be labelled as “source of ω-3”, “high in monounsaturated fat” and “high in unsaturated fats”. We can therefore conclude that feeding T. molitor with these agri-food by-products, especially from olive oil industry, enhanced the fatty acids profile of their fat fraction.
Enrichment of peat with a protein hydrolysate-based biostimulant obtained from wine lees: effect on pepper plants
(Taylor & Francis AS, 2025) Tejada Moral, Manuel; López-Rodríguez, Jesús; Gómez Parrales, Isidoro Ángel; Paneque Macías, Patricia Isabel; Navarro Torre, Salvadora; Orts Gómez, José María; Parrado Rubio, Juan; Cristalografía, Mineralogía y Química Agrícola; Microbiología y Parasitología; Bioquímica y Biología Molecular; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Union (UE)
Currently, the use of biostimulants is considered an environmentally friendly alternative to synthetic fertilizers. In this work, we investigated the use of a biostimulant obtained from winemaking sludge by enzymatic hydrolysis processes in peat enrichment. The aim was to observe how this biostimulant affects the growth and development of green pepper (Capsicum annuum L. cv. Italian) seedlings. The biostimulant was applied in three doses (1, 2, and 3 g/L) for a total of four applications. Seedlings were harvested at a height of 8–16 cm and with 5–7 leaves. Plant height, weight of aboveground and belowground parts, macro- and micronutrient contents, photosynthetic pigments in leaves, and enzymes related to plant stress were determined. The results obtained indicated that plant height, weight of the aboveground and belowground parts, and macro- and micronutrient content in the aboveground and root parts were higher in plants treated with the highest dose of biostimulant. Compared with the control treatment (without amendments), the contents of chlorophyll a, chlorophyll b, and total carotenoids increased by 57%, 51.9%, and 53.1%, respectively, in plants treated with the highest dose of biostimulant. These results suggest that peat enrichment with this biostimulant could be useful for improving bell pepper quality

Examinar

Envíos recientes