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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)

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The immune system: uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares mar Cuadrado-Tejedor ana García-Osta Juan José Lasarte Immunology and Immunotherapy Program Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Division of Gene Therapy for Neurological Disorders Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Pathology Anatomy and Physiology Department School of Medicine University of NavarraIDISNA

Humans and animals use the classic five senses-sight, hearing, touch, smell, and taste-to detect and monitor their environment, with the sense of position and movement often referred to as the sixth sense. The perception of external signals through the senses is essential to an organism’s survival, transmitting signals to the central nervous system(CNS) and prompting physiological changes in other biological systems. In addition to the direct effects of sense-induced mediators in the brain,

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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

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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 *** 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

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Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

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World Journal of Gastroenterology 2024年第11期30卷 1545-1555页

作者： Juan Pablo Stefanolo Verónica Segura martina Grizzuti Abel Heredia Isabel Comino ana Florencia Costa Roberto Puebla maría Paz Temprano Sonia Isabel Niveloni Gabriel de Diego maría E Oregui Edgardo Gustavo Smecuol Mauricio C de marzi Elena F Verdú Carolina Sousa Julio César Bai Small Bowel Section Department of MedicineGastroenterology Hospital of Buenos Aires“Dr.C.Bonorino Udaondo”Buenos Aires 1264Argentina Department of Microbiology and Parasitology Faculty of PharmacyUniversity of SevilleSeville 41080Spain Department of Medicine Dr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1264Argentina Basic and Applied Research Group in Immunology and Bioactives(GIBAIB) Institute of Ecology and Sustainable Development(INEDES)National University of LujanLuján 6700Buenos AiresArgentina Department of Medicine Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamilton L8S 4L8OntarioCanada Facultad de Medicina Universidad del SalvadorBuenos Aires C1051ABBArgentina

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant *** To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual *** This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term *** a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or *** endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of *** samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and *** Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol ***,628/640(98.1%)stool samples were *** was undetectable(0.32μg/g)to potentially cause mucosal *** GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in ***-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP *** with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific *** This exploratory study conducted in a real-life setting revealed high adherence to the *** AN-PEP treatment did not significantly reduce the overall GIP stool ***,given the observation of a significantly lower prevale

关键词： Celiac disease Aspergillus niger prolyl endoprotease Gluten immunogenic peptides Trial Symptoms Real-life trial

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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

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Hydroxytyrosol and Parkinson's disease:protective actions against alpha-synuclein toxicity

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Neural Regeneration Research 2024年第7期19卷 1427-1428页

作者： Ruth Hornedo-Ortega ana M.Espinosa-Oliva Departamento de Nutrición y Bromatología Toxicología y Medicina LegalFacultad de FarmaciaUniversidad de SevillaSevilleSpain Instituto de Biomedicina de Sevilla IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Departamento de Bioquímica y Biología Molecular Facultad de FarmaciaUniversidad de SevillaSevillaSpain

Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of *** to data from the World Health Organization(WHO),its prevalence has doubled in the past 25 *** 2019,global estimates indicated over 8.5 million individuals with PD and it is suggested that PD caused 329000 deaths,an increase of over 100% since 2000(WHO,2022).

关键词： protective Alzheimer prevalence

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Design multifunctional Mg–Zr coatings regulating Mg alloy bioabsorption

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Journal of Magnesium and Alloys 2024年第4期12卷 1461-1478页

作者： Zohra Benzarti Sandesh Itani JoséDavid Castro Sandra Carvalho ana Sofia Ramos University of Coimbra CEMMPREARISEDepartment of Mechanical EngineeringRua Luís Reis Santos3030-788CoimbraPortugal Laboratory of Multifunctional Materials and Applications(LaMMA) Department of PhysicsFaculty of Sciences of SfaxUniversity of SfaxSoukra Road km 3.5B.P.1171Sfax3000Tunisia

Magnesium(Mg)alloys are widely used for temporary bone implants due to their favorable biodegradability,cytocompatibility,hemocompatibility,and close mechanical properties to ***,rapid degradation and inadequate strength limit their *** overcome this,the direct current magnetron sputtering technique is employed for surface coating in Mg-based alloys using various zirconium(Zr)*** approach presents a promising strategy for simultaneously improving corrosion resistance,maintaining biocompatibility,and enhancing strength without compromising *** leveraging Mg’s inherent biodegradability,it has the potential to minimize the need for secondary surgeries,thereby reducing costs and *** paper is a systematic study aimed at understanding the corrosion mechanisms of Mg–Zr coatings,denoted Mg-xZr(x=0–5 at.%).Zr-doped coatings exhibited columnar growth leading to denser and refined structures with increasing Zr *** analysis confirmed the presence of the Mg(00.2)basal plane,shifting towards higher angles(1.15°)with 5 at.%Zr doping due to lattice parameter changes(i.e.,decrease and increase of“c”and“a”lattice parameters,respectively).Mg–Zr coatings exhibited“liquidphilic”behavior,while Young’s modulus retained a steady value around 80 GPa across all ***,the hardness has significantly improved across all samples’coating,reaching the highest value of(2.2±0.3)GPa for 5 at.%*** testing in simulated body fluid(SBF)at 37℃ revealed a significant enhancement in corrosion resistance for Mg–Zr coatings containing 1.0–3.4 at.%*** with the 5 at.%Zr coating which exhibited a corrosion rate of 32 mm/year,these coatings displayed lower corrosion rates,ranging from 1 to 12 mm/*** synergistic enhancement in mechanical properties and corrosion resistance,achieved with 2.0–3.4 at.%Zr,suggests potential ability for reducing stress shielding and controlled degradation performance,and consequentl

关键词： Mg-Zr coatings Magnetron sputtering Nanoindentation Corrosion resistance Bone implants

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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

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Impact of Microstructural and Surface Modifications on the Ti-45Nb Alloy’s Response to Bio-Environment

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Acta Metallurgica Sinica(English Letters) 2024年第7期37卷 1215-1230页

作者： Ivana Cvijović-Alagić Slađana Laketić MilošMomčilović Jovan Ciganović Jelena Bajat Vesna Kojić Vinča Institute of Nuclear Sciences-National Institute of the Republic of Serbia University of BelgradeMike Petrovića Alasa 12-1411000BelgradeSerbia Faculty of Technology and Metallurgy University of BelgradeKarnegijeva 411000BelgradeSerbia Oncology Institute of Vojvodina Faculty of MedicineUniversity of Novi SadPut Doktora Goldmana 4Sremska Kamenica21204Sremska KamenicaSerbia

The Ti-45Nb (mass%) alloy’s corrosive and biocompatible response in simulated physiological conditions was investigated before and after its additional high-pressure torsion (HPT) and laser irradiation processing. The grain size reduction from 2.76 µm to ~ 200 nm and the appearance of laser-induced morphologically altered and highly oxidized surface led to the significant improvement of alloy corrosion resistance and cell–implant interaction. Moreover, an additional increase of the laser pulse energy from 5 to 15 mJ during the alloy irradiation in the air led to an increase in the surface oxygen content from 13.64 to 23.89% accompanied by an increase of excellent cell viability from 127.18 to 134.42%. As a result of the controlled alloy microstructural and surface modifications, the formation of protective bi-modal mixed Ti- and Nb-oxide external scale was enabled. The presence of this surface oxide scale enhanced the alloy’s resistance to corrosion deterioration and simultaneously boosted cell viability and proliferation.

关键词： Ti-45Nb alloy High-pressure torsion Laser surface scanning Corrosion resistance Biocompatible properties

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