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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 diseases.We identified QN 19,a simple,low molecular weight nitrone,that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde.Quinolylnitrone 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 kinetics.Compound 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 disease.In 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 coordination.Importantly,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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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 people.Global change is composed of multiple factors that affect the population differently,having a very significant impact in the Mediterranean area.Human beings,through their actions,try to mitigate this impact and thus generate a more resilient society.Extreme hydro-logical events are affected by this climate change,with torrential rainfall events and severe droughts becoming frequent.Understanding these trends will allow us to better adapt to future conditions.This study aims to analyse catastrophic floods and severe droughts from paleo studies to studies that focus on future projections.For 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 situation.studies 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 each.In 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 change.It 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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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 conservation.Recent studies using adaptive setpoint temperatures incorporate international models from AsHRAE standard 55 and EN16798-1.This study,however,has instead considered a regional Brazilian adaptive comfort model.This 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 temperatures.All 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 simulations.The 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,respectively.It 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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Morphometry and Mineral Content in the seeds and soil of Two species of Argemone L.(Papaveraceae)in the Central Part of the Chihuahuan Desert

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Phyton-International Journal of Experimental Botany 2024年第2期93卷 371-386页

作者： Perla Patricia Ochoa-garcía Jaime sánchez-salas Ricardo Trejo-Calzada Jesús JosafathQuezada-Rivera Fabián garcía-González Unidad Regional Universitaria de ZonasÁridas BermejilloUniversidad Autónoma ChapingoDurango35230México Facultad de Ciencias Biológicas Universidad Juárez del Estado de DurangoGómez PalacioDurango35010México

The genus Argemone L.(Papaveraceae)is found widely distributed in Mexico’s Chihuahuan Desert(CD).some species of this genus are of phytochemical or ethnobotanical interest.They are inedible plants considered as scrubs.To date they have not been broadly studied;thus,their ecology is,to our knowledge,unknown.The present work was centered around carrying out a morphometric analysis and the determination of minerals in the soil and seeds of the wild populations of Argemone at sites belonging to two ecoregions of the CD in Mexico.In April 2021 and April 2022,seeds of Argemone spp.,and soil samples were collected at 10 sites of the CD.The seeds were selected under a randomized design,and weight,length,diameter,thickness,buoyancy,and mineral content were determined.The soil samples were obtained under the Mexican regulation NOM-021-RECNAT-2000,and determinations of mineral content,electrical conductivity,apparent density,and soluble anions were performed.The information obtained was grouped by variable,species,and place of precedence.The statistical tests consisted of an ANOVA,Tukey means tests considering p≤0.05,and a Principal Components Analysis.Argemone pleiacantha exhibited differences in terms of weight(F=54.79,p=0.001),length(F=90.83,p=0.001),thickness(F=104.89,p=0.001),and diameter(F=155.82,p=0.001),and the differences in Argemone mexicana were in weight(F=46.71,p=0.001),thickness(F=187.49,p=0.001),length(F=191.56,p=0.001),and diameter(F=215.83,p=0.001).The evaluated seeds reached their maximal imbibition velocity at 24 h of evaluation.The content of the micro-and macro-nutrients analyzed in the seeds and soil suggest a tight relation with the morphometric characteristics of the seeds.

关键词： Micronutrients agricultural area semiarid zone ecoregion buoyancy

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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 cations.This fact allows the cost-effective,large-scale generation of microscopic and macroscopic protein materials with intriguing biomedical properties.Among such materials,resulting from the simple bioproduction of protein building blocks,homomeric nanoparticles are of special value as multivalent interactors and drug carriers.Interestingly,we have here identified that the assembly of a given His-tagged protein might render distinguishable categories of self-assembling protein nanoparticles.This 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 blocks.In one of them,the assembling and disassembling is controllable by cations.However,a second population immediately self-assembles upon purification through a non-regulatable pathway,rendering larger nanoparticles with specific biological properties.The structural analyses of both model proteins and nanoparticles revealed important conformational variability in the building blocks.This fact renders different structural and functional categories of the final soft materials resulting from the participation of energetically unstable intermediates in the oligomerization process.These 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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Peripheral nerve regeneration through nerve conduits evokes differential expression of growth-associated protein-43 in the spinal cord

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Neural Regeneration Research 2023年第8期18卷 1852-1856页

作者： Jesús Chato-Astrain Olga Roda David sánchez-Porras Esther Miralles Miguel Alaminos Fernando Campos Óscar Darío garcía-garcía Víctor Carriel Department of Histology(Tissue Engineering Group) University of GranadaInstituto de Investigación Biosanitaria ibs.GRANADAGranadaSpain Department of Human Anatomy and Embryology University of GranadaGranadaSpain Unit of Clinical Neurophysiology University Hospital San CecilioGranadaSpain

Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regeneratin

关键词： growth-associated protein 43(GAP-43) immunohistochemistry nerve guide nerve tissue regeneration peripheral nerve repair spinal cord tissue engineering

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A fuzzy cognitive map-based algorithm for predicting water consumption in spanish healthcare centres

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Building simulation 2023年第11期16卷 2193-2205页

作者： Gonzalo sánchez-Barroso Jaime González-Domínguez Joao Paulo Almeida-Fernandes Justo garcía-sanz-Calcedo Engineering Projects Area University of ExtremaduraAv.Elvas06006BadajozSpain Department of Paisagem Ambiente e OrdenamentoUniversity of EvoraR.Romão Ramalho7000-650ÉvoraPortugal

The management of water consumption in healthcare centres can have positive impacts on both the environmental performance and profitability of health systems.Computational tools assist in the decision-making process of managing the operation and maintenance of healthcare centres.This research aimed to integrate the empirical knowledge of experts in Healthcare Engineering and the historical data from 66 healthcare centres in a Fuzzy Cognitive Map.The outputs of the predictive model included water consumption,water cost,and CO_(2) emissions in healthcare facilities,along with eleven variables to discover the causes and consequences of water consumption in healthcare centres.A healthcare centre with about 12350 users,located in a city that experiences an average of 1100 heating degree days,whose facilities be moderately energy-efficient contributing over 50%with renewable energies is expected to consume 8.4 dam^(3) of water with 32.1 k€of cost,and contribute realising 30.8 ton CO_(2)eq emissions.The use of Fuzzy Cognitive Maps for prediction can provide a high level of effectiveness in identifying the factors that contribute to water consumption and in designing key performance indicators to manage the environmental performance of healthcare buildings.This tool is extremely effective in enhancing the performance of the management division of health systems.

关键词： water consumption Fuzzy Cognitive Maps healthcare centres Healthcare Engineering water management

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Influence of different sports on fat mass and lean mass in growing girls

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Journal of sport and Health science 2017年第2期6卷 213-218页

作者： Esther Ubago-Guisado Esmeralda Mata Javier sánchez-sánchez María Plaza-Carmona María Martín-garcía Leonor Gallardo IGOID Research Group University of Castilla-La Mancha Toledo 45071 Spain GENUD Toledo Research Group University of Castilla-La Mancha Toledo 45071 Spain school of sport UCAM Universidad Catoica San Antonio Murcia 30107 Spain

Purpose: The aim of this study was to analyze and compare the effects of different sports(swimming, football, basketball, and handball) on fat mass and lean mass in prepubertal and pubertal girls.Methods: Two hundred girls(10.6 ± 1.5 years old, Tanner stages I–III) participated in the study and were divided into 5 groups: 40 swimmers, 40 football players, 40 basketball players, 40 handball players, and 40 controls. Fat and lean masses at whole body, arms, trunk, and legs were measured using dual-energy X-ray absorptiometry(DXA). Pubertal status was determined using Tanner test. Effects of different sports on fat and lean masses were assessed through analysis of covariance with height as covariates. Analyses were performed separately in 2 groups depending on the Tanner stage(prepubertal and pubertal).Results: The girls of the control group had less lean mass and more fat mass compared to the girls who play sports(p s in body fat between sports. The swimmers and football players had less body fat(p s showed the highest values in lean mass(p sion: Impact sports(football, basketball, and handball) and low-impact sports(swimming) provide an appropriate development of lean mass in growing girls. We can conclude that people practicing sports at early ages ensure a lower fat mass and higher lean mass compared to those who do not practice. These results may be useful as a preventive method of adult obesity.

关键词：运动员体脂肪肉质量发育期青春期骨密度仪预防方法女孩

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Thermokinetic and conductivity analyzes of the high CO2 chemisorption on Li5AlO4 and alkaline carbonate impregnated Li5AlO4 samples:Effects produced by the use of CO2 partial pressures and oxygen addition

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Journal of Energy Chemistry 2017年第5期26卷 919-926页

作者： Pedro sánchez-Camacho J.Francisco Gómez-garcía Heriberto Pfeiffer Laboratorio de Fisicoquímica y Reactividad de superficies(LaFRes) Instituto de Investigaciones en MaterialesUniversidad Nacional Autońoma de MexicoCircuito exterior s/nCd.UniversitariaDel.Coyoacan C.P.04510Ciudad de Me´xicoMexico

The effect of COpartial pressure was evaluated during the COchemisorption in penta lithium aluminate（LiAlO）, using different COand Opartial pressures in the presence or absence of alkaline carbonates. Results showed that using low PO（0.1） did not affect the kinetic and final COchemisorption process. Moreover, small additions of oxygen（PO= 0.05） into the mixture flue gas, seemed to increase the COchemisorption. Additionally, the presence of alkaline carbonates modified the COcapture temperature range. COchemisorption kinetic parameters were determined assuming a double exponential model where direct COchemisorption and COchemisorption controlled by diffusion processes are considered.Finally, ionic diffusion was analyzed by ionic conduction analysis, where all the gravimetric and ionic measurements were in good agreement showing different diffusion processes depending on temperature.Finally, the oxygen and alkaline carbonate additions have positive effects during the COchemisorption process in LiAlO, and a possible reaction mechanism is presented.

关键词： CO2 capture Thermogravimetric analysis Partial pressure Ionic conduction

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Mitochondrial phylogeography and molecular evolution of the rhodopsin visual pigment in troglobitic populations of Astyanax mexicanus(De Filippi,1853)

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Zoological Research 2023年第4期44卷 761-775页

作者： Marco A.A.Garduño-sánchez Vladimir de Jesus-Bonilla silvia Perea Ramses Miranda-Gamboa Andrea Herrera-garcía Mauricio de la Maza Benignos Claudia Patricia Ornelas-garcía Colección Nacional de Peces Departamento de ZoologíaInstituto de BiologíaUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoC.P.04510México Posgrado en Ciencias Biológicas Colección Nacional de PecesDepartamento de ZoologíaInstituto de BiologíaUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoC.P.04510México Licenciatura en Ciencias Forenses Facultad de MedicinaUniversidad Nacional Autónoma de MéxicoCiudad UniversitariaCoyoacánMéxico CityC.P.04510México Instituto de Energías Renovables Universidad Nacional Autónoma de MéxicoTemixcoMorelos C.P.62580Mexico Facultad de Ciencias Biológicas Universidad Autónoma de Nuevo LeónCiudad UniversitariaSan Nicolás de los GarzaNuevo LeónC.P.66450México

Cave-adapted animals provide a unique opportunity to study the evolutionary mechanisms underlying phenotypic,metabolic,behavioral,and genetic evolution in response to cave environments.The Mexican tetra(Astyanax mexicanus)is considered a unique model system as it shows both surface and cave-dwelling morphs.To date,at least 33 different cave populations have been identified,with phylogenetic studies suggesting an origin from at least two independent surface lineages,thereby providing a unique opportunity to study parallel evolution.In the present study,we carried out the most exhaustive phylogeographic study of A.mexicanus to date,including cave and surface localities,using two mitochondrial markers(cytochrome b(cyt b)and cytochrome c oxidase subunit I(COI))and nuclear rhodopsin visual pigment(rho).Additionally,we inferred the molecular evolution of rho within the two contrasting environments(cave and surface)and across three geographic regions(sierra de El Abra,sierra de Guatemala,and Micos).In total,267 individuals were sequenced for the two mitochondrial fragments and 268 individuals were sequenced for the rho visual pigment from 22 cave and 46 surface populations.Phylogeographic results based on the mitochondrial data supported the two-lineage hypothesis,except for the Pachón and Chica caves,whose introgression has been largely documented.The sierra de El Abra region depicted the largest genetic diversity,followed by the sierra de Guatemala region.Regarding the phylogeographic patterns of rho,we recovered exclusive haplogroups for the sierra de El Abra(Haplogroup I)and sierra de Guatemala regions(Haplogroup IV).Moreover,a 544 bp deletion in the rho gene was observed in the Escondido cave population from sierra de Guatemala,reducing the protein from seven to three intramembrane domains.This change may produce a loss-of-function(LOF)but requires further investigation.Regarding nonsynonymous(dN)and synonymous(ds)substitution rates(omega valuesω),our results revealed the prevailing influence of purifying selection

关键词： Visual pigments selection Cavefish Vision loss Loss of function

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