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8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

Acta Pharmaceutica sinica B 2023年第5期13卷 2152-2175页

作者： Damijan Knez Daniel Diez-Iriepa Mourad Chioua Andrea Gottinger Milica Denic Fabien Chantegreil Florian Nachon Xavier Brazzolotto Anna skrzypczak-Wiercioch Ane Meden Anja Pilar Janko Kos simon akelj Jure stojan Kinga saat Julia serrano Ana Patricia Fernández aitana sánchez-garcía Ricardo Martínez-Murillo Claudia Binda Francisco López-Muoz stanislav Gobec JoséMarco-Contelles University of Ljubljana Faculty of PharmacyLjubljana 1000Slovenia Laboratory of Medicinal Chemistry(Institute of Organic Chemistry CSIC)Madrid 28006Spain Departamento de Química Orgánicay Química Inorgánica Alcaláde HenaresMadrid 28871Spain Department of Biology and Biotechnology University of PaviaPavia 27100Italy Département de Toxicologie et Risques Chimiques Institut de Recherche Biomédicale des ArméesParis 91220France Department of Animal Anatomy and Preclinical sciences University Centre of Veterinary Medicine JU-UAUniversity of Agriculture in KrakowKrakow 30-059Poland Institute of Biochemistry Faculty of MedicineUniversity of LjubljanaLjubljana 1000Slovenia Department of Pharmacodynamics Chair of PharmacodynamicsFaculty of PharmacyJagiellonian University Medical CollegeKrakow 30-688Poland Department of Translational Neurobiology Neurovascular Research GroupCajal Institute(CSIC)Madrid 28002Spain Biotechnology and Vegetal Biology Department Escuela Técnica Superior de Ingeniería AgronómicaAlimentaria y de BiosistemasUniversidad Politécnica de MadridMadrid 28040Spain Faculty of Health Camilo JoséCela University of Madrid(UCJC)Neuropsychopharmacology Unit“Hospital 12 de Octubre”Research InstituteMadrid 28692Spain

We describe the development of quinolylnitrones(QNs)as multifunctional ligands inhibiting cholinesterases(ChEs:acetylcholinesterase and butyrylcholinesterase—h BChE)and monoamine oxidases(hMAO-A/B)for the therapy of neurodegenerative *** identified QN 19,a simple,low molecular weight nitrone,that is readily synthesized from commercially available *** 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition,yet unexpectedly showed potent inhibition of h BChE(IC50=1.06±0.31 nmol/L)and h MAO-B(IC_(50)=4.46±0.18μmol/L).The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding,which was further studied by enzyme *** 19 acted as a free radical scavenger and biometal chelator,crossed the blood—brain barrier,was not cytotoxic,and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's *** addition,in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and ***,chronic treatment of double transgenic APPswe-Ps1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice,underscoring the disease-modifying effect of QN 19.

关键词： Quinolylnitrone Butyrylcholinesterase Monoamine oxidase B Alzheimer's disease Multifunctional ligands 6-Hydroxydopamine model Passive avoidance task Novel object recognition

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Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural Regeneration Research 2025年第10期20卷 2915-2916页

作者： Andrea Bartolomé-Nafría Javier garcía-Pardo salvador Ventura Institut de Biotecnologia i de Biomedicina(IBB)and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-stafshede,2023).

关键词： structure amyloid

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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco garcía-garcía Victoria Moreno-Manzano Consuelo Guerri María Pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MsC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MsC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

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Green ionic metal-organic frameworks as nanocatalysts for CO_(2)fixation

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Nano Research 2025年第1期18卷 260-269页

作者： Nuria Martín Miguel Maireles-Porcar Julián sánchez Velandia Belén Altava Francisco G.Cirujano Eduardo garcía-Verdugo Departamento de Química Inorgánica y Orgánica Universidad Jaume IAv.Sos Baynats/nCastellóde la PlanaCastellón 12071Spain

Co,Ni,and Zn iso-reticular coordination polymers of 2,5-dihydroxyterphthalic acid(H_(2)dot)can be rapidly obtained under room temperature and aqueous conditions using either sodium or ammonium hydroxide as the bases to deprotonate the *** use of metal bromides and tetrabutylammonium hydroxide(TBAOH)as the base allows the green synthesis of ionic metal-organic frameworks(MOFs),characterized by X-ray diffraction(XRD),Fourier transform infrared(FTIR),scanning electron microscopy(sEM),thermo gravimetric analysis(TGA),H-nuclear magnetic resonance(NMR),elemental analysis,and X-ray photoelectron spectroscopy(XPs),and employed in the pressure,solvent,and additive-free CO_(2)fixation to epoxides by its cycloaddition to epichlorohydrin,exhibiting a cooperative behavior between the MOF and the ionic liquid formed within the framework,achieving TONs of the confined tetrabutylammonium bromide(TBABr)up to 700.

关键词： metal-organic frameworks(MOFs) ionic liquids heterogeneous catalysis CO_(2)conversion

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Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： Marta garcía-Juan Mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“severo Ochoa”(CsIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

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Assessing the energy saving potential of using adaptive setpoint temperatures:The case study of a regional adaptive comfort model for Brazil in both the present and the future

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Building simulation 2024年第3期17卷 459-482页

作者： Daniel sánchez-garcía David Bienvenido-Huertas Carlos Rubio-Bellido Ricardo Forgiarini Rupp Department of Electrical Engineering University Carlos III of MadridMadridSpain Department of Building simulation ZEROCEM SLSevilleSpain Department of Building Constructions University of GranadaGranadaSpain Department of Building Constructions II University of SevilleSevilleSpain section of Design for sustainability Department of Civil and Mechanical EngineeringTechnical University of DenmarkKgs.LyngbyDenmark

It has been found in recent years that using setpoint temperatures based on adaptive thermal comfort models is a successful method of energy *** studies using adaptive setpoint temperatures incorporate international models from AsHRAE standard 55 and *** study,however,has instead considered a regional Brazilian adaptive comfort *** study investigates the energy demand arising from the use of a local Brazilian comfort model in order to assess the energy implications from the use of the worldwide AsHRAE standard 55 adaptive model and various fixed setpoint *** of Brazil’s climate zones,full air-conditioning,mixed-mode building operating modes,present-day climate change scenarios,and future scenarios—specifically Representative Concentration Pathways(RCP)2.6,4.5,and 8.5 for the years 2050 and 2100—have all been taken into account in building energy *** use of adaptive setpoint temperatures based on the Brazilian local model considering mixed-mode has been found to significantly reduce energy consumption when compared to static setpoint temperatures(average energy-saving values ranging from 52%to 58%)and the AsHRAE 55 adaptive model(average values ranging from 15%to 21%).Considering climate change and the mixed-mode Brazilian model,the overall energy demand for the three groups of climatic zones(annual average outdoor temperatures≤21℃,>21 and≤25℃and>25℃)ranged between 2%decrease and 5%increase,4%and 27%increase,and 13%and 45%increase,*** is concluded as a consequence that setting setpoint temperatures based on the Brazilian local adaptive comfort model is a very efficient energy-saving method.

关键词： adaptive thermal comfort building energy simulation energy efficiency climate change adaptive setpoint temperatures local comfort mode

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Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype

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World Journal of Gastroenterology 2016年第11期22卷 3165-3174页

作者： Antonio Madejón Míriam Romero ángela Hernández Araceli garcía-sánchez Marta sánchez-Carrillo Antonio Olveira Javier garcía-samaniego Hepatology section Gastroenterology Department Hospital Universitario La Paz 28046 Madrid Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas (CIBERehd) 28046 Madrid Spain Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ) 28046 Madrid Spain

AIM: To study the hepatitis B virus(HBV) and hepatitis D virus(HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV ***: We conducted a transversal study including 68 chronic hepatitis delta(CHD)(37 HIVpositive) patients and a control group of 49 chronic hepatitis B(CHB)(22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B(HBs Ag) serum titers were analyzed with the Monolisa HBs Ag Ultra system(Bio-Rad), using as quantification standard a serial dilution curve of an international HBs Ag standard. serum HBV-DNA titers were analyzed using the Roche Cobas Taq Man(Roche, Barcelona, spain), and the serum HDV-RNA using an in-house real-time q RT-PCR method, with Taq Man probes. HBV genotype was determined with the line immunoassay Li PA HBV genotyping system(Innogenetics, Ghent, Belgium). In those patients negative for Li PA assay, a nested PCR method of complete HBs Ag coding region, followed by sequence analysis was ***: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median(IQR): 1.25(1.00-1.35) vs 2.95(2.07-3.93) log10(copies/m L), P = 0.013] and HIV positive patients [2.63(1.24-2.69) vs 7.25(4.61-7.55) log10(copies/m L), P s was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with Li PA assay. Finally, the HBs Ag titers reflected no significant differences in CHD patients infected with HBV-A or ***: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E.

关键词： Hepatitis D virus Hepatitis B virus Delta hepatitis Replication interference Viral replication

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social Network-Aware Interfaces as Facilitators of Innovation

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Journal of Computer science & Technology 2012年第6期27卷 1211-1221页

作者： Elena garcía-Barriocanal Miguel-Angel sicilia salvador snchez-Alonso Computer science Department University of Alcal'aCtra.Barcelona km.33.600Alcala' de Henares 28871Spain

Achieving continuous innovation in organizations requires a balance between exploiting yet acquired knowledge and exploring new knowledge. In addition to having the adequate resources, change and innovation capabilities require specific management support and organizational structures. Recent research has pointed out the importance of social network structure and of the activity of agents that work across domains or disciplines in the innovation-oriented behaviour of organizations. As a consequence, information systems should ideally be able to support the analysis, development and management of such social structure for the benefit of organizational objectives. Current social network interfaces provide an established mental model to workers that can be hypothesized to be adequate for supporting activities that foster innovative behaviour. That behaviour is facilitated through exposing the activities of other workers across organizational structures. This paper reports on the design of a user interface specifically targeted to manage the social aspects of innovation based on some aspects of Hargadon＇s model of innovation and knowledge brokering. The emergent nature of interactions in social network sites is used as the metaphor to foster situated cognition. The interface design assessment is described and some metrics for innovative behaviour that could be derived for such an interface are sketched.

关键词： information system innovation learning ontology-based information system social network

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Human-environmental interaction with extreme hydrological events and climate change scenarios as background

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Geography and sustainability 2022年第3期3卷 232-236页

作者： Carlos sánchez-garcía Marcos Francos PaleoRisk Research Group Geography DepartmentFaculty of Geography and HistoryUniversity of BarcelonaBarcelonaEspaña IPHEs Catalan Institute for Human Palaeoecology and social Evolution TarragonaEspaña Department of Geography Faculty of Geography and HistoryUniversity of SalamancaCervantes s/n37002SalamancaSpain Centro de Investigación de Estudios Avanzados del Maule(CIEAM) Universidad Católica del MauleAv.San Miguel 36053466706TalcaChile

Climate change significantly impacts the lives of all *** change is composed of multiple factors that affect the population differently,having a very significant impact in the Mediterranean *** beings,through their actions,try to mitigate this impact and thus generate a more resilient *** hydro-logical events are affected by this climate change,with torrential rainfall events and severe droughts becoming *** these trends will allow us to better adapt to future *** study aims to analyse catastrophic floods and severe droughts from paleo studies to studies that focus on future *** this purpose,a search for information has been carried out through other studies over the last five years to have a current perspective of this *** point to changes in the dynamics of floods and droughts,not only worsening the extremes but also affecting the average values of the records of *** addition,the studies point out that anthropic action is accelerating the changes,with human beings and their capacity to adapt being infe-rior to the velocity of this global *** is necessary to generate a paradigm shift in terms of global production by trying to adapt to future extreme flood and drought hazards.

关键词： Climate change Flood hazard Human disaster management Historical floods

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The spectrum of building block conformers sustains the biophysical properties of clinically-oriented self-assembling protein nanoparticles

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science China Materials 2022年第6期65卷 1662-1670页

作者： Eric Voltà-Durán Julieta M sánchez Hèctor-López-Laguna Eloi Parladé Laura sánchez-garcía Alejandro sánchez-Chardi Ario de Marco Ugutz Unzueta Esther Vázquez Antonio Villaverde Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra 08193BarcelonaSpain Departament de Genètica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra 08193BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN) Bellaterra 08193BarcelonaSpain Instituto de Investigaciones Biológicas y Tecnológicas(IIBYT)(CONICET-Universidad Nacional de Córdoba) ICTA&Cátedra de Química BiológicaDepartamento de QuímicaFCEFyNUNC.Av.Velez Sarsfield 1611X 5016GCA CórdobaArgentina servei de Microscòpia Universitat Autònoma de BarcelonaBellaterra 08193BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciències AmbientalsFacultat de BiologiaUniversitat de Barcelona08028 BarcelonaSpain Laboratory for Environmental and Life sciences University of Nova GoricaNova Gorica 5000Slovenia Biomedical Research Institute sant Pau(IIB sant Pau) Sant Antoni Ma Claret 16708025 BarcelonaSpain

Histidine-rich peptides confer self-assembling properties to recombinant proteins through the supramolecular coordination with divalent *** fact allows the cost-effective,large-scale generation of microscopic and macroscopic protein materials with intriguing biomedical *** such materials,resulting from the simple bioproduction of protein building blocks,homomeric nanoparticles are of special value as multivalent interactors and drug ***,we have here identified that the assembly of a given His-tagged protein might render distinguishable categories of self-assembling protein *** fact has been scrutinized through the nanobody-containing fusion proteins EM1-GFP-H6 and A3C8-GFP-H6,whose biosynthesis results in two distinguishable populations of building *** one of them,the assembling and disassembling is controllable by ***,a second population immediately self-assembles upon purification through a non-regulatable pathway,rendering larger nanoparticles with specific biological *** structural analyses of both model proteins and nanoparticles revealed important conformational variability in the building *** fact renders different structural and functional categories of the final soft materials resulting from the participation of energetically unstable intermediates in the oligomerization *** data illustrate the complexity of the Hismediated protein assembling in recombinant proteins but they also offer clues for a better design and refinement of protein-based nanomedicines,which,resulting from biological fabrication,show an architectonic flexibility unusual among biomaterials.

关键词： recombinant proteins self-assembling protein materials nanoparticles biomaterials

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