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Browsing by browse.metadata.contributordepartment "Bioquímica y Biología Molecular B e Inmunología"

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    1. Introduction to Neurochemistry
    (2026) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología; Facultades de la UMU::Facultad de Química
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    10. Brain ischemia
    (2026) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    11. Chronic and neurodegenerative diseases
    (2026) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    12. Neuropsychiatric diseases
    (2026) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    13. Neurochemical absis of drug addiction
    (2026) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    2. Cerebral Metabolism
    (2026-07-06) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    4-octyl itaconate reduces NLRP3 inflammasome constitutive activation with cryopyrin-associated periodic syndrome p.R262W, p.D305N and p.T350M variants
    (Springer, Birkhäuser Verlag, 2025-05-23) Molina-López, Cristina; Hurtado-Navarro, Laura; O'Neill, Luke A.J.; Pelegrín Vivancos, Pablo; Bioquímica y Biología Molecular B e Inmunología
    Cryopyrin-associated periodic syndrome (CAPS) is a condition characterized by dominant genetic variants in the NLRP3 gene, leading to the formation of constitutively active inflammasomes. These inflammasomes play a crucial role in the inflammatory episodes experienced by CAPS patients, primarily driven by the production of interleukin (IL)-1. Although treatment with IL-1 blockers is effective for CAPS, some patients develop refractory responses and adverse reactions to these therapies. Consequently, there is a need for novel treatments for CAPS patients. Promising candidates are the derivatives of itaconate, which have been shown to impair NLRP3 inflammasome activation and IL-1 release in blood mononuclear cells from CAPS patients. In this study, we provide insight into the inhibitory mechanisms of the itaconate derivative 4-octyl itaconate (4-OI) on NLRP3 with different (p.R262W, p.D305N and p.T350M) gain-of-function mutations associated with CAPS. Notably, 4-OI effectively blocks the basal auto-activation of the inflammasome formed by NLRP3 p.R262W, p.D305N and p.T350M variants, resulting in reduced caspase-1 activation, gasdermin D processing, and IL-18 release. Furthermore, after lipopolysaccharide priming of macrophages, 4-OI also decreases IL-1 gene expression and release. Overall, 4-OI impairs CAPS p.D305N-associated inflammasome function at multiple levels, and therapeutic agents based on itaconate could be a promising therapeutic approach to managing inflammatory episodes in CAPS patients carrying p.R262W, p.D305N or p.T350M variants.
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    4. Neurotransmitters, synthesis and functional roles
    (2026-07-06) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    5. Neuropeptidergic transmission, steroids and endocannabinoids
    (2026-07-06) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    6. Neuronal plasticity
    (2026-07-06) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    7. Sensory Neurons
    (2026-07-06) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    8. Neurochemistry of motor activity and sleep-wake rythm
    (2026) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    9. Neuroinflammation
    (2026) Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    A compressive review about Taxol® : history and future challenges
    (MDPI, 2020-12-17) Gallego Jara, Julia; Lozano Terol, Gema; Cánovas Díaz, Manuel; Diego Puente, Teresa de; Gallego Jara, Julia; Sola Martínez, Rosa Alba; Bioquímica y Biología Molecular B e Inmunología
    Taxol®, which is also known as paclitaxel, is a chemotherapeutic agent widely used to treat different cancers. Since the discovery of its antitumoral activity, Taxol® has been used to treat over one million patients, making it one of the most widely employed antitumoral drugs. Taxol® was the first microtubule targeting agent described in the literature, with its main mechanism of action consisting of the disruption of microtubule dynamics, thus inducing mitotic arrest and cell death. However, secondary mechanisms for achieving apoptosis have also been demonstrated. Despite its wide use, Taxol® has certain disadvantages. The main challenges facing Taxol® are the need to find an environmentally sustainable production method based on the use of microorganisms, increase its bioavailability without exerting adverse effects on the health of patients and minimize the resistance presented by a high percentage of cells treated with paclitaxel. This review details, in a succinct manner, the main aspects of this important drug, from its discovery to the present day. We highlight the main challenges that must be faced in the coming years, in order to increase the effectiveness of Taxol® as an anticancer agent.
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    A genetically encoded IL-1β BRET sensor to monitor inflammasome activity
    (Asociación Americana de Inmunología, 2012) Compan, Vincent; Baroja-Mazo, Alberto; Bragg, Laricia; Verkhratsky, Alexei; Perroy, Julie; Pelegrín Vivancos, Pablo; Bioquímica y Biología Molecular B e Inmunología
    Inflammation is fundamental for protecting the organism against infection and injury. However, a failure to control immune response results in chronic inflammation and several associated disorders such as pain and loss of function. Initiation of inflammation is orchestrated by cytokines, among which interleukin (IL)-1β is particularly important. IL- 1β is synthesized as an inactive protein that has to be processed by the inflammasome to generate the mature bioactive form. Conventional techniques cannot monitor IL-1β activation with high spatial and temporal resolution. Here, we present a ratiometric biosensor that allows monitoring IL-1β processing in real-time, with a temporal resolution of seconds and with a single cell spatial resolution. Using this sensor, we describe for the first time the kinetic of the inflammasome activity in living macrophages. With this new probe we also demonstrated that the pro-IL-1β processing occurs all over the cytoplasm.
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    A green chemo-enzymatic approach for CO2 capture and transformation into bis(cyclic carbonate) esters in solvent-free media
    (American Chemical Society, 2024-10-02) Ruiz, Francisco J.; Velasco, Francisco; Porcar, Raul; Garcia Verdugo, Eduardo; Villa Aroca, Rocío; Lozano Rodríguez, Pedro; Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
    A sustainable approach for CO2 capture and chemo-enzymatic transformation into bis(cyclic carbonate) esters from CO2, glycidol and organic anhydrides under solvent-free conditions has been demonstrated. The chemo-enzymatic process is based in two consecutive catalytic steps, which can be executed through separated operations, or within a one-pot combo system, taking advantage of the synergic effects that emerge from integrating ionic liquid (ILs) technologies and biocatalysts. In a first step, lipase-catalyzed transesterification and esterification reactions of different diacyl donors (e.g. glutaric anhydride, succinic anhydride, dimethyl succinate, etc.) with glycidol in solvent-free under mild reaction conditions (70 °C, 6 h), producing the corresponding diglycidyl esters derivatives up to 41% yield. By a second step, the synthesis of bis(cyclic carbonate) esters was carried out as results of the cycloaddition reaction of CO2 (from an exhausted gas source, 15% CO2 purity) on these diglycidyl esters, catalyzed by the covalently attached 1-decyl-2-methylimidazolium IL (Supported Ionic Liquid-Like Phase, SILLP), in solvent-free, leading up to 65% yield after 8 h at 50 °C and 1MPa CO2 pressure. Both key elements of the reaction system (biocatalyst and SILLP) were successfully recovered and reused for at least 5 operational cycles. Finally, different metrics have been applied to assess the greenness of the solvent-free chemo-enzymatic synthesis of bis(cyclic carbonate) esters here reported.
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    A new class of aggregation inhibitor of amyloid-beta peptide based on green tea catechins
    Nieto Cerón, Susana; Bioquímica y Biología Molecular B e Inmunología
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    A novel CD14high CD16high subset of peritoneal macrophages from cirrhotic patients is associated to an increased response to LPS
    (Elsevier, 2016-03-01) Fernández-Fernández, María Dolores; Tristán-Manzano, María; Sánchez-Velasco, Eduardo; Miras-López, Manuel; García-Penarrubia, Pilar; Hernández Caselles, Trinidad; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Tapia Abellán, Ana; Bioquímica y Biología Molecular B e Inmunología
    The aim of this study was to characterize monocyte-derived macrophages (M-DM) from blood and ascites of cirrhotic patients comparatively with those obtained from blood of healthy controls. The phenotypic profile based on CD14/CD16 expression was analyzed by flow cytometry. Cells were isolated and stimulated in vitro with LPS and heat killed Candida albicans. Phosphorylation of ERK, c-Jun, p38 MAPK, and PKB/Akt was analyzed by Western blotting. A novel CD14(high)CD16(high) M-DM subpopulation is present in ascites (∼33%). The CD14(++)CD16(+) intermediate subset is increased in the blood of cirrhotic patients (∼from 4% to 11%) and is predominant in ascites (49%), while the classical CD14(++)CD16(-) subpopulation is notably reduced in ascites (18%). Basal hyperactivation of ERK and JNK/c-Jun pathways observed in ascites M-DM correlates with CD14/CD16 high expressing subsets, while PI3K/PKB does it with the CD16 low expressing cells. In vitro LPS treatment highly increases ERK1/2, PKB/Akt and c-Jun phosphorylation, while that of p38 MAPK is decreased in M-DM from ascites compared to control blood M-DM. Stimulation of healthy blood M-DM with LPS and C. albicans induced higher phosphorylation levels of p38 than those from ascites. Regarding cytokines secretion, in vitro activated M-DM from ascites of cirrhotic patients produced significantly higher amounts of IL-6, IL-10 and TNF-α, and lower levels of IL-1β and IL-12 than control blood M-DM. In conclusion, a new subpopulation of CD14(high)CD16(high) peritoneal M-DM has been identified in ascites of cirrhotic patients, which is very sensitive to LPS stimulation.
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    A Side-by-Side comparison of wildtype and variant melanocortin 1 receptor signaling with emphasis on protection against oxidative damage to DNA.
    (MDPI, 2023-09-21) Sánchez-Beltrán, José; Abrisqueta, Marta; Padilla, Lidia; Herraiz Serrano, Cecilia María; Cerdido Ochoa, Sonia; García-Borrón Martínez, José Carlos; Herraiz Serrano, Cecilia María; Jiménez-Cervantes Frigols, Celia; Lambertos Escudero, Ana; Olivares Sánchez, María Concepción; Bioquímica y Biología Molecular B e Inmunología
    Common variants of the MC1R gene coding the α-melanocyte stimulating hormone receptor are associated with light skin, poor tanning, blond or red hair, and increased melanoma risk, due to pigment-dependent and -independent effects. This complex phenotype is usually attributed to impaired activation of cAMP signaling. However, several MC1R variants show significant residual coupling to cAMP and efficiently activate mitogenic extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling. Yet, residual signaling and the key actions of wildtype and variant MC1R have never been assessed under strictly comparable conditions in melanocytic cells of identical genetic background. We devised a strategy based on CRISPR-Cas9 knockout of endogenous MC1R in a human melanoma cell line wildtype for BRAF, NRAS and NF1, followed by reconstitution with epitope-labeled MC1R constructs, and functional analysis of clones expressing comparable levels of wildtype, R151C or D294H MC1R. The proliferation rate, shape, adhesion, motility and sensitivity to oxidative DNA damage were compared. The R151C and D294H RHC variants displayed impaired cAMP signaling, intracellular stability similar to the wildtype, triggered ERK1/2 activation as effectively as the wildtype, and afforded partial protection against oxidative DNA damage, although less efficiently than the wildtype. Therefore, common melanoma-associated MC1R variants display biased signaling and significant genoprotective activity.
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    Acidophilic granulocytes of the marine fish gilthead seabream (Sparus aurata L.) produce interleukin-1b following infection with Vibrio anguillarum
    (Springer, 2004) Chaves-Pozo, Elena; García-Castillo, Jesús; Meseguer, José; García Ayala, Alfonsa; Mulero Méndez, Victoriano Francisco; Pelegrín Vivancos, Pablo; Bioquímica y Biología Molecular B e Inmunología
    The fish immune response to Gram-negative bacteria is poorly understood. In this study, we use a monoclonal antibody (mAb) specific to acidophilic granulocytes from the marine fish gilthead seabream (Sparus aurata L.), together with an antiserum specific to interleukin-1b (IL-1b) from this species, in order to investigate whether these cells are involved in the immune response against the pathogenic bacterium Vibrio anguillarum and, in particular, in the production of the pro-inflammatory cytokine IL-1b. We found that gilthead seabream head- kidney, peritoneal exudate and peripheral blood leukocytes accumulated proIL-1b intracellularly when challenged in vitro with V. anguillarum, whereas only peritoneal exudate and blood leukocytes were able to accumulate proIL-1b following infection. Importantly, the blood leukocytes from infected animals that accumulated proIL-1b were shown to be the acidophilic granulocytes. A rapid mobilization of such cells from the head-kidney to the site of inflammation following infection with V. anguillarum was also observed.
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