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protein glycation:a wolf in sweet sheep’s clothing behind neurodegeneration

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neural Regeneration Research 2024年第5期19卷 975-976页

作者： ana B.Uceda Francisco Leal-pérez Miquel Adrover Institut Universitari d’Investigacióen Ciències de la Salut(IUnICS) Institut d’InvestigacióSanitària Illes Balears(IdISBa) Departament de Química Universitat de les Illes BalearsCtraPalma de MallorcaSpain

At the beginning of the 16th century,paracelsus coined the maxim:“the dose makes the poison”.This principle can be applied to all living organisms,including organs and *** brain and its glial and neuronal cells are ... 详细信息

关键词： organs sheep sweet

Standardizing MI-TLIF, a proposal for a Reproducible Technique

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Open Journal of Modern neurosurgery 2024年第2期14卷 91-103页

作者： Iván Ulises Sámano López Jesús Alberto pérez Contreras Emmanuel Cantú chávez Diana chávez Lizárraga ana Sofía peña Blesa Thania Karina Gutiérrez Anchondo Á ngeles Pedregal Ciudad de México México

Background: Minimally invasive transforaminal lumbar interbody fusion (MI TLIF) is a widely known and performed technique, however its versatility among different physicians continues to hinder its replication and results. Therefore, this study aimed to provide a step-by-step surgical guide to perform a safe MI-TLIF, based on the results obtained in patients operated on by a single surgeon over a period of 12 years. patients and methods: A retrospective, single center, longitudinal, and observational cohort study was conducted with 931 patients who underwent MI TLIF by a single surgeon between 2010 and 2022 using the technique described on this paper, each with a minimum follow-up of 12 months. Criteria included Schizas classification, listhesis according to Meyerding classification, number of levels treated, cage size, and complications (screw repositioning or cerebrospinal fluid leak). patient clinical outcomes were assessed using the Oswestry Disability Index (ODI), Visual analog Scale (VAS) for pre- and postoperative radicular pain. Thin slice CT scans were used to assess the progression of the fusion using the Bridwell classification. In the statistical analysis, percentages, median, and interquartile range (IQR) were calculated. Results: nine hundred and thirty one patients underwent MI TLIF using the technique described, eight hundred and eighty (94.5%) had a single level treated and fifty one (5.5%) had a 2 level procedure (982 levels), an 8mm cage was placed on five hundred and seventeenlevels (52.7%), six hundred and sixty three levels(67.6%) achieved grade I fusion, two hundred and sixty six levels (27.1%) achieved grade II fusion, 52 levels (5.3) achieved grade III fusion and one level (0.1) achieved a grade IV fusion or non-union. Revision surgery was performed on 3 patients (0.3%) for screw repositioning, cerebrospinal fluid leak was present on 2 patients during surgery and treated before closure. VAS scores and ODI were improved at 12 months postop (V

关键词： MITLIF Lumbar Interbody Fusion Technique pain Relief and Disability

Academic Stress Assessment Using Virtual Reality as an Educational Tool in Spine Surgery

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Open Journal of Modern neurosurgery 2024年第2期14卷 114-123页

作者： Diana chávez Lizárraga Jesús Alberto pérez Contreras Fernando Alvarado Gómez Evelyn Quintero Medina Emmanuel Cantú chávez Iván Ulises Sámano López ana Sofía peña Blesa Department of neurosurgery ángeles Pedregal Ciudad de México México Department of Traumatology and Orthopedics Hospital Santa Fe Bogotá Colombia

Introduction: The evaluation of academic stress in medical students and residents is a topic of significant interest, given the considerable challenges they face during their learning process with traditional teaching methods. The use of technologies like virtual reality presents an opportunity to enhance their skills through simulations and training. The main objective of this study is to qualitatively assess the stress levels experienced by medical students and residents by integrating virtual reality into their current learning methods, aiming to improve their ability to manage stressors in their practice. Material and Methods: A questionnaire was conducted with 12 medical students and 12 Traumatology and orthopedics residents. The purpose of the questionnaire was to evaluate the levels of academic stress using the SISCO inventory. The stress levels were calculated by transforming average values into percentages, and the following criteria were assigned: 0 to 33% for Mild Stress, 34 to 66% for Moderate Stress, and 67 to 100% for Deep Stress. Then, a virtual reality class focused on spine surgery was provided. Both medical students and residents were trained using the non nocere SharpSurgeon software platform and Oculus Quest 2 virtual reality glasses. At the end of the session, a second questionnaire related to the practice with virtual reality was conducted with the same evaluation criteria and a comparative analysis was carried out. Results: 12 undergraduate students from Hospital Angeles Mexico, CDMX and 12 traumatology and orthopedics residents at Hospital Santa Fe, Bogota were evaluated. The students in CDMX reported an average qualitative stress of 28.50% during habitual practices, which decreased to an average of 14.67% after virtual reality practice. Residents in Bogotá experienced an average qualitative stress of 30.50% with their current learning methods but this reduced to an average of 13.92% after using virtual reality. These findings indicate that t

关键词： Virtual Reality Academic Stress Learning Strategies Spine Surgery Training

Impacts of pI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón pérez-núñez María Fernanda González ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(pI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the pI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/pI3K/AKT/connexin 43,and notch/pI3K/AKT *** targeting the inactivation of the pI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the pI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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 ***,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain *** may be especially important for 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 *** plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective *** has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory *** 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

Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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nano Research 2024年第10期17卷 9111-9125页

作者： ana M.López-Estévez Y.Zhang María Medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart nicola G.A.Abrescia María J.Vicent Defang Ouyang Dolores Torres María José Alonso Center for Research in Molecular Medicine and chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key Laboratory of Quality Research in chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China polymer Therapeutics Laboratory and CIBEROnC prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses Lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain ALBA Synchrotron Light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(Hanas)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).Hanas composed by an mAb,modified HA and phosphatidylcholine(pC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed Hanas’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of Hanas technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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 *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** 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 *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** 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 *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** 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 ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,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 ***,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 *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

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

A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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Military Medical Research 2024年第2期11卷 228-267页

作者： Miguel A.Ortega Oscar Fraile-Martinez Cielo García-Montero Sergio Haro Miguel Ángel Álvarez-Mon Diego De Leon-Oliva ana M.Gomez-Lahoz Jorge Monserrat Mar Atienza-pérez David Díaz Elisa Lopez-Dolado Melchor Álvarez-Mon Department of Medicine and Medical Specialities University of Alcala28801 Alcala de HenaresSpain Ramón y Cajal Institute of Sanitary Research(IRYCIS) 28034 MadridSpain Department of psychiatry and Mental Health Hospital Universitario Infanta Leonor28031 MadridSpain Service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain Immune System Diseases‑Rheumatology Service and Internal Medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this ***(pnIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a *** initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and *** the present review,we will explore the most important local and systemic consequences of SCI from a pnIE perspective,defining the changes occurring in each system and how all these mechanisms are ***,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

关键词： Spinal cord injury(SCI) psychoneuroimmunoendocrinology(pnIE) Secondary injury Immunoinflammatory dysfunction Gut microbiota Translational opportunities

Thermal properties and high-temperature ablation of high-entropy (Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating on graphite substrate

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Journal of Advanced Ceramics 2024年第8期13卷 1268-1281页

作者： ana C.Feltrin Daniel Hedman Farid Akhtar Division of Materials Science Lulea University of TechnologyLulea 97187Sweden Center for Multidimensional Carbon Materials(CMCM) Institute for Basic Science(IBS)Ulsan 44919Republic of Korea

An entropy-stabilized multicomponent ultrahigh-temperature ceramic(UHTC)coating,(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2),on a graphite substrate was in-situ sintered by spark plasma sintering(Sps)from constituent transition metal diboride ***(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating had a hardness of 31.2±2.1 Gpa and resisted 36.9 Gpa of stress before delamination,as observed at the *** temperature-dependent thermal properties of the multicomponent diboride(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) were obtained by molecular dynamics(MD)simulations driven by a machine learning force field(MLFF)trained on density functional theory(DFT)*** thermal conductivity,density,heat capacity,and coefficient of thermal expansion obtained by the MD simulations were used in time-dependent thermal stress finite element model(FEM)*** low thermal conductivity(ponent diboride coupled with its similar coefficient of thermal expansion to that of graphite indicated that stresses of less than 10 Gpa were generated at the interface at high temperatures,and therefore,the coating was mechanically resistant to the thermal stress induced during *** experiments at 220℃ showed that the multicomponent diboride coating was resistant to thermal stresses with no visible cracking or *** ablation mechanisms were mechanical denudation and evaporation of B_(2)O_(5) and light V-Ti oxides,which caused a decrease in the mass and thickness of the coating and resulted in mass and linear ablation rates of-0.51 mg·s^(-1) and -1.38μm·s^(-1),respectively,after 60 *** findings demonstrated the thermal and mechanical stability of multicomponent entropy-stabilized diborides as coatings for carbon materials in engineering components under extreme environments.

关键词： entropy-stabilized diborides ultrahigh temperature ceramics molecular dynamics(MD)simulations density functional theory(DFT) ablation properties