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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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Effect of caffeine in the intraventricular hemorrhage of the preterm newborn

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Neural Regeneration Research 2023年第9期18卷 1942-1943页

作者： pilar Alves-Martinez Monica Garcia-Alloza Division of Physiology School of MedicineUniversidad de CadizCadizSpain Biomedical Research and Innovation Institute of Cádiz(INiBICA)Research Unit Puerta del Mar University Hospital University of CadizCadizSpain

There are around 15 million preterm newborns(PT) eve ry year(Atienza-Navarro et al., 2020).With these figures in mind,prematurity represents a major health problem worldwide and it is a leading cause of infant mortality,accounting for up to 35%of all deaths among newborns(Atienza-Navarro et al.,2020) and up to 18% of the deaths among children under 5 years of age.

关键词： newborn infant deaths

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Extracorporeal shockwave lithotripsy in the management of urinary stones: New concepts and techniques to improve outcomes

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Asian Journal of Urology 2024年第2期11卷 143-148页

作者： pilar Bahilo-Mateu Alberto Budia-Alba Lithotripsy and Endourology Unit La Fe University and Polytechnic HospitalValenciaSpain Lithotripsy and Endourology Unit Urology DepartmentLa Fe University and Polytechnic HospitalValenciaSpain

Objective: Extracorporeal shockwave lithotripsy (SWL) currently plays an important role in the treatment of urinary tract lithiasis. The purpose of this article was to describe new concepts and procedural strategies that would improve results using SWL as a treatment for urolithiasis, thereby achieving better clinical practice.Methods: A systematic review process was carried in PubMed/PMC from January 2003 to March 2023. A narrative synthesis of the most important aspects has been made.Results: The important recommendations for the adequate selection of the candidate patient for treatment with SWL are summarized, as well as the new strategies for a better application of the technique. Aspects about intraoperative position, stone localization and monitoring, analgesic control, machine and energy settings, and measures aiming at reduced risk of complications are described.Conclusion: To achieve the therapeutic goal of efficient stone disintegration without increasing the risk of complications, it is necessary to make an adequate selection of patients and to pay special attention to several important factors in the application of treatment. Technological development in later generation devices will help to improve current SWL results.

关键词： Lithotripsy Extracorporeal shockwave Stone disease Treatment Urinary stone

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Interleukin 6 and interferon gamma haplotypes are related to cytokine serum levels in dogs in an endemic Leishmania infantum region

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Infectious Diseases of Poverty 2023年第1期12卷 62-70页

作者： LuisÁlvarez Pablo-Jesús Marín-García pilar Rentero-Garrido Celia pilar Martinez-Jimenez Lola Llobat Department of Animal Production and Health Public Health and Food Science and TechnologyVeterinary Medicine FacultyFacultad de VeterinariaUniversidad Cardenal Herrera-CEUCEU UniversitiesValenciaSpain Precision Medicine Unit INCLIVA Biomedical Research InstituteValenciaSpain Helmholtz Pioneer Campus(HPC) Helmholtz Zentrum MünchenNeuherbergGermany

Background The Ibizan Hound is a canine breed native to the Mediterranean region,where leishmaniasis is an endemic zoonosis.Several studies indicate a low prevalence of this disease in Ibizan Hound dogs,whereas other canine breeds present a high prevalence.However,the underlying molecular mechanisms still remain unknown.The aim of this work is to analyse the relationship between serum levels of cytokines and the genomic profiles in two canine breeds,Ibizan Hound(resistant canine breed model)and Boxer(susceptible canine breed model).Methods In this study,we analyse the haplotypes of genes encoding cytokines related to immune response of Leishmania infantum infection in twenty-four Boxers and twenty-eight Ibizan Hounds apparently healthy using CanineHD DNA Analysis BeadChip including 165,480 mapped positions.The haplo.glm extension of haplo.score was used to perform a General Linear Model(GLM)regression to estimate the magnitude of individual haplotype effects within each cytokine.Results Mean levels of interferon gamma(IFN-γ),interleukin 2(IL-2)and IL-18 in Boxer dogs were 0.19±0.05 ng/ml,46.70±4.54 ng/ml,and 36.37±30.59 pg/ml,whereas Ibizan Hound dogs present 0.49±0.05 ng/ml,64.55±4.54 ng/ml,and 492.10±31.18 pg/ml,respectively.The GLM regression shows fifteen haplotypes with statistically significant effect on the cytokine serum levels(P<0.05).The more relevant are IL6-CGAAG and IFNG-GCA haplotypes,which increase and decrease the IL-2,IL-8 and IFN-γserum levels,respectively.Conclusions Haplotypes in the IFNG and IL6 genes have been correlated to serum levels of IFN-γ,IL-2 and IL-18,and a moderate effect has been found on IL8 haplotype correlated to IL-8 and IL-18 serum levels.The results indicate that the resistance to L.infantum infection could be a consequence of certain haplotypes with a high frequency in the Ibizan Hound dog breed,while susceptibility to the disease would be related to other specific haplotypes,with high frequency in Boxer.Future studies are needed to elucidate whether these differences and h

关键词： Cytokine Haplotype Dog Immune response Regulatory mechanism Resistance Susceptibility

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Heritage Conservation in Postcolonial India

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Built Heritage 2022年第1期6卷 110-112页

作者： pilar M.Guerrieri Department DASTU Politecnico Di MilanoEdoardo Bonardi32013320133 MilanoMIltaly

Heritage Conservation in Postcolonial India.Approaches and Challenges,edited by Manish Chalana and Ashima Krishna,is very rich,and counts thirteenth different con-tributors among urban and architectural conservationists,urban and historic preservation plan-ners,landscape designers and architects,social entrepre-neurs,experts in cultural heritage from universities,social and research institutions.

关键词： architectural landscape coloni

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Current status of the genetic susceptibility in attenuated adenomatous polyposis

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World Journal of Gastrointestinal Oncology 2019年第12期11卷 1101-1114页

作者： Víctor Lorca pilar Garre Laboratorio de Oncología Molecular Grupo de Investigación Clínica y Traslacional en OncologíaHospital Clínico San CarlosMadrid 28040Spain Laboratorio de Oncología Molecular Servicio de OncologíaHospital Clínico San CarlosMadrid 28040Spain

Adenomatous polyposis(AP)is classified according to cumulative adenoma number in classical AP(CAP)and attenuated AP(AAP).Genetic susceptibility is the major risk factor in CAP due to mutations in the known high predisposition genes APC and MUTYH.However,the contribution of genetic susceptibility to AAP is lower and less understood.New predisposition genes have been recently proposed,and some of them have been validated,but their scarcity hinders accurate risk estimations and prevalence calculations.AAP is a heterogeneous condition in terms of severity,clinical features and heritability.Therefore,clinicians do not have strong discriminating criteria for the recommendation of the genetic study of known predisposition genes,and the detection rate is low.Elucidation and knowledge of new AAP high predisposition genes are of great importance to offer accurate genetic counseling to the patient and family members.This review aims to update the genetic knowledge of AAP,and to expound the difficulties involved in the genetic analysis of a highly heterogeneous condition such as AAP.

关键词： Attenuated adenomatous polyposis Genetic susceptibility High predisposition gene Genetic heterogeneity Colorectal cancer

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Circadian rhythms in the pathogenesis of gastrointestinal diseases

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World Journal of Gastroenterology 2018年第38期24卷 4297-4303页

作者： pilar Codonr-Franch Marie Gombert Department of Pediatrics Obstetrics and GinecologyUniversity of ValenciaValencia 46010Spain Department of Pediatrics Dr.Peset University HospitalValencia 46017Spain Department of Biotechnology University of La RochelleLa Rochelle 17000France

The etiology of digestive pathologies such as irritable bowel syndrome(IBS), inflammatory bowel diseases(IBD) and cancer is not yet fully understood. In recent years, several studies have evidenced circadian variations in mechanisms involved in digestive health. In situations of disturbed circadian rhythms(chronodisruption) where the central clock and the peripheral clocks receive incoherent signals, the synchronicity is lost producing implications for health. This lack of coordination could alter the tissue function and cause long term damage to the organs. Life habits such as sleep, physical exercise, social interaction, and feeding times are determinants for stability and integrity of circadian rhythms. In recent years, experimental and clinical studies have consistently evidenced that the alteration of circadian rhythms is associated with the development of digestive pathologies mainly linked to dismotility or changes in microbiota composition. Likewise, it seems reasonable to deep into the importance of chronodisruption as a factor that may participate in the development of pathologies such as IBS, IBD and digestive cancers. Moreover, life habits respecting circadian rhythms should be promoted for the prevention of these diseases. Further studies will allow us a better understanding of the mechanisms acting at molecular level, and the development of new therapeutic targets.

关键词： Circadian rhythms Gastrointestinal diseases Irritable bowel syndrome Inflammatory bowel disease Digestive cancers

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One-Generated Nilpotent Bicommutative Algebras

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Algebra Colloquium 2022年第3期29卷 453-474页

作者： Ivan Kaygorodov pilar Páez-Guillán Vasily Voronin Centro de Matemática e Aplicacōes Universidade da Beira InteriorCovilhãPortugal Institute of Mathematics and Mathematical ModelingAlmatyKazakhstan University of Santiago de Compostela Santiago de CompostelaSpain University of ViennaViennaAustria Novosibirsk State University NovosibirskRussia

We give a classification of 5-and 6-dimensional complex one-generated nilpotent bicommutative algebras.

关键词： bicommutative algebras nilpotent algebras algebraic classification central extension

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Minimization of methabenzthiazuron residues in leaching water using amended soils and photocatalytic treatment with TiO_2 and ZnO

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Journal of Environmental Sciences 2014年第4期26卷 757-764页

作者： Jos Fenoll pilar Flores pilar Hellín Joaquín Hern'andez Simón Navarro Department of Food Quality Murcia Institute of Agri-Food Research and Development Department of Agricultural Chemistry Geology and Pedology School of Chemistry University of Murcia Campus Universitario de Espinardo

In the present work, potential groundwater pollution by methabenzthiazuron （MTBU） and the effect of three different amendments （composted sheep manure, composted pine bark and spent coffee grounds） on its mobility were investigated under laboratory conditions. The efficiency of ZnO and TiO2 suspensions in the photocatalytic degradation of MTBU in leaching water was also investigated. The relative and cumulative breakthrough curves were obtained from disturbed soil columns. The presence and/or addition of organic matter drastically reduced the movement of the herbicide. On other hand, photocatalytic experiments showed that the addition of ZnO and TiO2 strongly enhances the degradation rate of this herbicide compared with the results of photolytic experiments under artificial light. ZnO appeared to be more effective in MTBU oxidation than TiO2. The results obtained point to the interest of using organic wastes and heterogeneous photocatalysis for reducing the pollution of groundwater by pesticide drainage.

关键词： groundwater pollution organic amendment pesticide movement photocatalytic oxidation semiconductor oxides

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Role of selenium in type 2 diabetes,insulin resistance and insulin secretion

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World Journal of Diabetes 2023年第3期14卷 147-158页

作者： pilar Casanova Daniel Monleon Department of Pathology University of ValenciaValencia 46010Spain

Selenium is a trace mineral essential for life that acts physiologically through selenoproteins.Among other actions,the endogenous antioxidant selenoprotein glutathione peroxidase and the selenium transporter in blood,selenoprotein P,seem to play an important role in type 2 diabetes mellitus and insulin resistance by weakening the insulin signaling cascade through different mechanisms.Recent findings also suggest that selenoproteins also affect insulin biosynthesis and insulin secretion.This review discussed the role of selenium in type 2 diabetes and the complex interplay between selenoproteins and insulin pathways.

关键词： Selenium Diabetes Insulin resistance Metabolism Antioxidants

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