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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémartínez-Hernández Alejandro martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández ana Esther Moreno-martínez mar Cuadrado-Tejedor ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resil

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

Taurine: a promising nutraceutic in the prevention of retinal degeneration

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Neural Regeneration Research 2024年第3期19卷 606-610页

作者： Diego García-Ayuso Johnny Di Pierdomenico ana martínez-Vacas Manuel Vidal-Sanz Serge Picaud maría PVillegas-Pérez Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaEspaña Sorbonne Université INSERMCNRSInstitut de la VisionParisFrance

Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.

关键词： amino acid anti-inflammatory antioxidant gamma-aminobutyric acid nutraceutical photoreceptor degeneration retina retinitis pigmentosa taurine

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

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Neural Regeneration Research 2024年第2期19卷 296-301页

作者： Guillermo Estivill-Torrús ana Belen martínez-Padilla Lourdes Sánchez-Salido Anne Baron-Van Evercooren Beatriz García-Díaz Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma BIONAND) MálagaSpain Unidad Clínica de Neurociencias Hospital Regional Universitario de MálagaMálagaSpain Departamento de Biología Molecular y Bioquímica Universidad de MálagaSpain Sorbonne Université Institut du Cerveau-Paris Brain Institute-ICMINSERMCNRSAP-HPHôpital Pitié-SalpêtrièreParisFrance

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

关键词： cytokines dorsal root ganglia genetic factors neuropathic pain neurotrophic factors pharmacologic and nonpharmacologic therapies satellite glial cells sensory neurons

Synthesis and applications of lanthanoid complexes of pentadentate and hexadentate N_(5) and N_(6) macrocycles:A review

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Journal of Rare Earths 2024年第1期42卷 1-15,I0001页

作者： Julio Corredoira-Vázquez Cristina González-Barreira Paula Oreiro-martínez ana M.García-Deibe Jesús Sanmartín-Matalobos Matilde Fondo Departamento de Química Inorganica Facultade de QuímicaUniversidade de Santiago de CompostelaCampus Vida15782Santiago de CompostelaSpain Phantom-g CICECO-Aveiro Institute of MaterialsDepartment of PhysicsUniversity of Aveiro3810-193AveiroPortugal Institute of Materials(iMATUS) Universidade de Santiago de Compostela15782Santiago de CompostelaSpain

In this paper,the lanthanoid complexes of N_(5) and N_(6) macrocycle ligands,without pendant arms or additional heteroatoms,are surveyed.This review covers the period from 2015 to the current date,since in 2014 Schiff base macrocyclic ligands incorporating the pyridine moiety,and their complexes,were revised,and in 2015 the chemistry of pentaaza macrocycle ligands with rare earth metals was also summarized.Porphyrin and phthalocyanine ligands are not included in this review,which primarily focuses on complexes with Schiff bases and amines without pendant arms or any additional donor other than nitrogen.The synthetic methods,structural characterization,based on single X-ray crystal data,and properties of the lanthanoid complexes,with special attention to magneto-structural correlations,are presented herein.

关键词： Lanthanoid N_(5),N_(6)macrocycle Coordination chemistry Chirality Biological activity Molecule magnet

Dietary(poly)phenol intake is associated with cardiometabolic health parameters in adolescents

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Food Science and Human Wellness 2024年

作者： Emily P.Laveriano-Santos Sara Castro-Barquero Camila Arancibia-Riveros ana maría Ruiz-León Rosa Casas Ramón Estruch Patricia Bodega Mercedes de Miguel Amaya de Cos-Gandoy Jesús martínez-Gómez Gloria Santos-Beneit Juan M.Fernández-Alvira Rodrigo Fernández-Jiménez Rosa M.Lamuela-Raventós Anna Tresserra-Rimbau The Zena and Michael A.Wiener Cardiovascular Institute Icahn School of Medicine at Mount Sinai Department de Nutrició Ciències de l'Alimentació I Gastronomia XIA Facultat de Farmàcia i Ciències de l'alimentació Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB) Universitat de Barcelona Department of Internal Medicine Hospital Clínic Institutd'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) University of Barcelona Consorcio CIBER M.P.Fisiopatología de la Obesidad y Nutrición (CIBERObn) Instituto de Salud Carlos III (ISCIII) Mediterranean Diet Foundation 5. Foundation for Science Health and Education (SHE) 6. Centro Nacional de Investigaciones Cardiovasculares (CNIC) CIBER de Enfermedades Cardiovasculares (CIBERCV) 9. Hospital Universitario Clínico San Carlos

Background: The protective role of (poly)phenols against metabolic disorders has been extensively studied in adults but not in adolescents.Objective: To assess associations of dietary (poly)phenols and their subclasses with cardiometabolic health parameters in adolescents. Methods: A cross-sectional study was conducted in 944 individuals aged 11 to 14 years enrolled in the SI! Program for Secondary Schools trial (NCT03504059). (Poly)phenol intake was assessed using semi-quantitative food frequency questionnaires and the Phenol-Explorer database. The measured cardiometabolic parameters were waist circumference (WC) age-sex z-score， blood pressure (BP) age-sex z-score， blood glucose (BG)， triglycerides (TG)， and high-density lipoprotein cholesterol (HDL-c). Multilevel mixed-effect linear regression models were applied to examine the association between (poly)phenol quintiles and cardiometabolic health parameters.Results: Compared to the lowest quintile， adolescents in the highest quintile of total (poly)phenol intake had lower WC z-scores (β=-0.09， 95%CI=-0.09;-0.08， P-for trend=0.002)， mean arterial pressure z-scores (β =-0.11， 95%CI=-0.12;-0.09， P-for trend=0.206)， and HDL-c (β=-1.52， 95%CI=-2.90;-0.14， P-for trend=0.108)， after multivariable adjustment. The WC z-scores (β=-0.11， 95%CI=-0.19;-0.03， P-for trend=0.013) and HDL-c (β=-2.16， 95%CI=-3.78;-0.53， P-for trend=0.046) were lower in the highest quintile of flavonoid intake compared to the lowest quintile. The highest quintile of phenolic acid intake was associated with a lower WC z-score (β=-0.14， 95%CI=-0.26;-0.02， P-for trend=0.011) and TG levels (β=-8.83， 95%CI=-12.37;-5.30， P-for trend <0.001)， and the highest quintile of stilbene intake with lower BG (β=-1.83， 95%CI= -3.103;-0.64， P-for trend <0.001) and TG (β=-3.22， 95%CI= -4.95;-1.49， P-for trend=0.034)， and with higher HDL-c (β=2.328， 95%CI= 1.40;3.17， P-for trend=0.466) compared to the lowest quintile. Conclusion: A higher intake of (poly)phenols， especially flavonoids， phenolic acids， and stilbenes

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From Simulation to Reality: A Comprehensive Study on the Efficacy of a Rotating Monopolar and Bipolar Radiofrequency System through In-Silico Modeling and Pre-Clinical and Clinical Validation

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Journal of Biomedical Science and Engineering 2024年第6期17卷 107-128页

作者： Gregorio Viera Mármol ana Lorena Urbano Bojorge Alicia Robledo Jorge José Antonio Ferrández martínez Olalla Calvo Lozano High Technology Products S.L.U. (Sinclair) Barcelona Spain

Background: Skin aging is an unavoidable process aggravated by environmental agents. Among other energy devices, non-invasive radiofrequency (RF) technology is widely used for skin tightening and body contouring as it is simpler and more affordable than other technologies that also minimize pain and side-effects. However, most of the current RF devices do not provide automatic skin temperature control and it is difficult to achieve controlled, deep, and harmless thermal increase, so treatment performance and safety is dependent on the operator’s movements and expertise. Objective: To show the potential of numerical simulations for optimizing the design of monopolar and bipolar RF electrodes that are capable of providing homogeneous, deep and controlled heating. Materials and methods: In-silico models were developed and analyzed using Comsol Multiphysics software to simulate the RF effect produced in tissue by rotating monopolar and bipolar electrodes with different geometries from the Sculpt & Shape RF device (Sinclair, Spain), operating at frequencies of 0.5 and 1 MHz. Ex-vivo and in-vivo proof-of-concept tests were carried out to validate the simulations. Finally, treatments were performed on 16 subjects and a total of 78 body areas to assess the clinical results generated by the RF electrodes for skin tightening and body contouring. Results: In-silico studies emulated the superficial and deep dispersion of heat due to the release of RF energy into human skin tissue. The rotating electrodes (monopolar and bipolar) and the selected RF frequency (0.5 and 1 MHz) determined the homogeneity of the thermal distribution, the penetration depth (between 4.37 mm and 25.0 mm) and the heating dynamics (between 30 and 100 seconds to reach the target skin temperature), which were confirmed by ex-vivo and in-vivo tests. In addition, real treatments on facial and body areas using skin temperatures of between 43˚C and 44˚C showed consistent results with good clinical efficacy for skin tightening, circumference reduction and cel

关键词： Comsol Multiphysics Simulations Radiofrequency Skin Tightening Fat Reduction Body Contouring Cellulite

Taurine:an essential amino sulfonic acid for retinal health

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Neural Regeneration Research 2023年第4期18卷 807-808页

作者： Johnny Di Pierdomenico ana martínez-Vacas Serge Picaud maría P.Villegas-Pérez Diego García-Ayuso Departamento de Oftalmología Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca)MurciaSpain(Di Pierdomenico JMartínez-Vacas AVillegas-Pérez MPGarcía-Ayuso D)INSERMCNRSInstitut de la VisionSorbonne UniversitéParisFrance(Picaud S)

Taurine(2-amino-ethanesulfonic acid)is a naturally occurring amino sulfonic acid derived from cysteine and methionine metabolism.Its common name derives from the ox,as it was first isolated from the bile of an ox(Froger et al.,2014).The molecular structure of taurine differs from that of amino acids by the presence of a sulfonic acid,instead of the more common carboxylic acid group in the structure of amino acids.

关键词： sulfonic structure ethane

Machine learning insights concerning inflammatory and liver-related risk comorbidities in non-communicable and viral diseases

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World Journal of Gastroenterology 2022年第44期28卷 6230-6248页

作者： J Alfredo martínez marta Alonso-Bernáldez Diego martínez-Urbistondo Juan A Vargas-Nuñez ana Ramírezde Molina Alberto Dávalos Omar Ramos-Lopez Precision Nutrition and Cardiometabolic Health Madrid Institute of Advanced Studies-Food InstituteMadrid 28049Spain Department of Internal Medicine Hospital Universitario HM SanchinarroMadrid 28050Spain Servicio de Medicina Interna Hospital Universitario Puerta de Hierro MajadahondaMadrid 28222MajadahondaSpain Molecular Oncology and Nutritional Genomics of Cancer Madrid Institute of Advanced Studies-Food InstituteMadrid 28049Spain Laboratory of Epigenetics of Lipid Metabolism Madrid Institute of Advanced Studies-Food InstituteMadrid 28049Spain Medicine and Psychology School Autonomous University of Baja CaliforniaTijuana 22390Baja CaliforniaMexico

The liver is a key organ involved in a wide range of functions,whose damage can lead to chronic liver disease(CLD).CLD accounts for more than two million deaths worldwide,becoming a social and economic burden for most countries.Among the different factors that can cause CLD,alcohol abuse,viruses,drug treatments,and unhealthy dietary patterns top the list.These conditions prompt and perpetuate an inflammatory environment and oxidative stress imbalance that favor the development of hepatic fibrogenesis.High stages of fibrosis can eventually lead to cirrhosis or hepatocellular carcinoma(HCC).Despite the advances achieved in this field,new approaches are needed for the prevention,diagnosis,treatment,and prognosis of CLD.In this context,the scientific community is using machine learning(ML)algorithms to integrate and process vast amounts of data with unprecedented performance.ML techniques allow the integration of anthropometric,genetic,clinical,biochemical,dietary,lifestyle and omics data,giving new insights to tackle CLD and bringing personalized medicine a step closer.This review summarizes the investigations where ML techniques have been applied to study new approaches that could be used in inflammatoryrelated,hepatitis viruses-induced,and coronavirus disease 2019-induced liver damage and enlighten the factors involved in CLD development.

关键词： Machine learning Liver inflammation Liver disease Viral diseases Comorbidity

Risk Factors and Gender Differences for Depression in Chilean Older Adults:A Cross-Sectional analysis from the National Health Survey 2016–2017

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International Journal of Mental Health Promotion 2022年第5期24卷 679-697页

作者： Gabriela Nazar Carlos-maría Alcover Yeny Concha-Cisternas Igor Cigarroa Ximena Díaz-martínez mariela Gatica-Saavedra Fabián Lanuza ana maría Leiva-Ordónez maría Adela martínez-Sanguinetti Miquel martorell Fanny Petermann-Rocha Claudia Troncoso-Pantoja Carlos Celis-Morales Departamento de Psicología Facultad de Ciencias SocialesUniversidad de ConcepciónConcepciónChile Centro de Vida Saludable Universidad de ConcepciónConcepciónChile Departamento de Psicología Facultad de Ciencias de la SaludUniversidad Rey Juan CarlosMadridEspaña Pedagogía en Educación Física Facultad de EducaciónUniversidad AutónomaTalcaChile Escuela de Kinesiología Facultad de SaludUniversidad Santo TomásLosÁngelesChile Grupo de Investigación Calidad de Vida Departamento de Ciencias de la EducaciónUniversidad del BiobíoChillánChile Depto de Psiquiatría y Salud Mental Facultad de MedicinaUniversidad de ConcepciónConcepciónChile Centro de Epidemiología Cardiovascular y Nutricional(EPICYN) Facultad de MedicinaUniversidad de La FronteraTemucoChile Biomarkers and Nutrimetabolomics Laboratory Department of NutritionFood Sciences and GastronomyFood Technology Reference Net(XIA)Nutrition and Food Safety Research Institute(INSA)Faculty of Pharmacy and Food SciencesUniversity of BarcelonaBarcelona08028Spain Instituto de anatomía Histología y PatologíaFacultad de MedicinaUniversidad Austral de ChileValdiviaChile Instituto de Farmacia Facultad de CienciasUniversidad Austral de ChileValdiviaChile Departamento de Nutrición y Dietética Facultad de Farmacia.Universidad de ConcepciónConcepciónChile Facultad de Medicina Universidad Diego PortalesSantiagoChile BHF Glasgow Cardiovascular Research Centre Institute of Cardiovascular and Medical SciencesUniversity of GlasgowGlasgowUK Centro de Investigación en Educación y Desarrollo(CIEDE-UCSC).Departamento de Salud Pública Facultad de MedicinaUniversidad Católica de la Santísima ConcepciónConcepciónChile Laboratorio de Rendimiento Humano Grupo de Estudio en EducaciónActividad Física y Salud(GEEAFyS)Universidad Católica del MauleTalcaChile

Depressive disorders are recognized as one of the most common mental health conditions across different age groups.However,the risk factors associated with depression among older people from low-and middle-income countries remains unclear.This study aims to identify socio-demographic,health and psychosocial-related factors associated with depression in Chilean older adults.A cross-sectional study was carried out in a representative sample of 1,765 adults aged≥60 years participants from the Chilean National Health Survey 2016–2017.Depres-sion was assessed with the Composite International Diagnostic Interview(CIDI-SF).Associations between the exposure variables and depression were investigated using Poisson regression analyses.The mainﬁndings indi-cated that women showed higher likelihood of depression than men(Prevalence Ratio(PR)=2.6[95%CI:1.40;4.89]).An increased likelihood of depression was found in older adults with chronic pain,multimorbidity(≥2 diseases),previous diagnose of depression,high perception of stress,ﬁnancial stress,and difﬁculties for social par-ticipation.In women,higher likelihood of depression was found for those with the frailty phenotype(PR:8.53[95%CI:1.68;43.32]),rheumatoid arthritis(PR:2.41[95%CI:1.34;4.34]),insomnia(PR:2.99[95%CI:1.74;5.12])and low self-rated well-being(PR:4.94[95%CI:2.26;10.79]).Men who were divorced(PR:7.10[95%CI:1.44;34.90])or widowed(PR:10.83[95%CI:3.71;31.58]),obese(PR:5.08[95%CI:1.48;17.42])and who had asthma(PR:7.60[95%CI:2.31;24.99])were associated with higher odds of depression.The currentﬁndings may have clinical implications for the early identiﬁcation of older adults more susceptible to depression and also suggest the need to implement cultural and age-sensitive strategies to promote mental health in late life.

关键词： Depression older adults aging late-life depression risk factors