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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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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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Neural regeneration research 2025年第4期20卷 973-989页

作者： maría Belén Cieri Alberto Javier ramos Laboratorio de Neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain *** astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are *** altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional *** therapeutic strategies for traumatic brain injury are focused on preventing acute ***,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of *** this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with mirNAs or lncrNA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural regeneration research 2025年第8期20卷 2395-2407页

作者： maría Norte-Muñoz maría Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega mar Pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz maría Teresa Moreno-Flores marta Agudo-Barriuso 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 SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLrP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural regeneration research 2025年第4期20卷 1153-1163页

作者： Susana Mellado maría JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri maría Pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLrP3(NOD-,Lrr-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLrP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLrP3 inflammasome complex and other NLrs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and mirNAs(mir-21a-5p,mir-146a-5p,and mir-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of mir-21a-5p and mir-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLrP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,Lrr-and pyrin domain-containing protein 3(NLrP3)

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Olfactory receptors in neural regeneration in the central nervous system

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Neural regeneration research 2025年第9期20卷 2480-2494页

作者： rafael Franco Claudia Garrigós Toni Capó Joan Serrano-marín rafael rivas-Santisteban Jaume Lillo Molecular Neurobiology Laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain CiberNed Network Center for Biomedical research in Neurodegenerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain School of Chemistry Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Physiology School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental *** ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous *** gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent *** the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian *** ectopic expression provides insights into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing *** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative *** suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous syste

关键词： adenosine receptors adrenergic receptors ectopic expression G proteincoupled receptors glia neurons

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Prognostic impact of inflammatory and nutritional biomarkers in pancreatic cancer

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World Journal of Clinical Oncology 2025年第1期16卷 5-9页

作者： Macarena Teja maría I Garrido Abrahams Ocanto Felipe Counago Department of radiation Oncology GenesisCare-San Francisco de Asís University HospitalMadrid 28002Spain Department of radiation Oncology GenesisCare-Vithas La Milagrosa University HospitalMadrid 28010Spain National Director GenesisCare SpainMadrid 28043Spain Department of Medicine School of MedicineHealth and SportEuropean University of MadridMadrid 28670Spain

Pancreatic cancer is usually associated with a poor *** is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are *** et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLr),platelet-to-lymphocyte ratio(PLr),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NLr,and PLr and a hospital discharge of less than 15 *** a univariable analysis,PNI,SII,NLr and PLr were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall *** meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their ***,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant *** are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.

关键词： Inflammatory biomarkers Nutritional biomarkers Pancreatic cancer Prognosis Surgical complications

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c-Abl kinase at the crossroads of healthy synaptic remodeling and synaptic dysfunction in neurodegenerative diseases

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Neural regeneration research 2023年第2期18卷 237-243页

作者： Daniela A.Gutiérrez América Chandía-Cristi maría Joséyáñez Silvana Zanlungo Alejandra r.Alvarez Cell Signaling Laboratory Department of Cellular and Molecular BiologyCenter for Aging and Regeneration(CARE)Millennium Institute on Immunology and ImmunotherapyBiological Sciences FacultyPontificia Universidad Católica de ChileSantiagoChile School of Medical Technology Health Sciences FacultyUniversidad San SebastianSede Los LeonesSantiagoChile Department of Gastroenterology Faculty of MedicinePontificia Universidad Católica de ChileSantiagoChile

Our ability to learn and remember depends on the active formation,remodeling,and elimination of ***,the development and growth of synapses as well as their weakening and elimination are essential for neuronal *** structural reorganization of synaptic complexes,changes in actin cytos keleton and organelle dynamics,as well as modulation of gene expression,determine synaptic *** has been proposed that dys regulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative *** is known about downstream signaling of activated N-methyl-D-aspartate andα-amino-3-hydroxy-5-methyl-4-isoazolepro pionate receptors;howeve r,other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and *** non-receptor tyrosine kinase c-Abl(ABL1)is a key signal transducer of intra and extracellular signals,and it shuttles between the cyto plasm and the *** review focuses on c-Abl and its synaptic and neuronal ***,we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons,promoting the development of neurodegenerative ***,c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity,regulating dendritic spines remodeling and gene expression after cognitive training,and synaptic dysfunction and loss in neurodegenerative ***,c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice,but its absence provides dendritic spines resiliency against *** re,the present review has been designed to elu cidate the common links between c-Abl regulation of structural changes that involve the actin cytos keleton and organelles dynamics,and the transc riptional program activated during synaptic *** summarizing the recent discove ries on c-Abl functions,we aim to provide an overview of how

关键词： actin cytoskeleton activity-dependent plasticity Alzheimer's disease c-Abl dendritic spines learning synapse synaptic plasticity transcription tyrosine kinase

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The largest dengue outbreak in Argentina and spatial analyses of dengue cases in relation to a control program in a district with sylvan and urban environments

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Asian Pacific Journal of Tropical Medicine 2018年第3期11卷 227-234页

作者： Aníbal E Carbajo Alejandra rubio maría J Viani maría r Colombo Laboratorio de Eoclogía de Enfermedades Transmitidas por Vectores Instituto de Investigación e Ingeniería AmbientalUniversidad Nacional de General San Martín Consejo Nacional de Investigaciones Científicas y Técnicas Secretaria de Política Sanitaria y Desarrollo Humano Municipio de Tigre

Objective: To analyze the largest outbreak of dengue in Argentina in the municipality of Tigre during 2016, through detailed spatial analyses of the occurrence of cases in relation to demographic factors and vector control actions. Methods: Detailed and georreferenced data on dengue cases with laboratory results(NS1 or IgM) were analyzed. The occurrences of imported and autochthonous cases by census tract were modeled using demographic variables(population by age class, proportion of foreigners, proportion with university grade, proportion of males), dwelling variables(number of homes, proportion of dwellings with latrine, number of dwellings, proportion of houses, proportion of flats, proportion of slums) and census tract area as explanatory variables. The probability of occurrence of autochthonous and imported cases was modeled separately. The spatio-temporal occurrence of cases was studied in relation to focal and perifocal control actions(involving education campaigns, removal of Aedes aegypti breeding sites and exhaustive insecticide spraying) to assess the efficiency in stopping autochthonous cases spreading. results: All autochthonous cases occurred in the urban environment with no sylvan cases. The majority of the imported cases registered came from Paraguay and Northeastern Argentina. The age structure of imported and autochthonous cases did not differ from the age structure of the municipality, while that of the negative cases *** studied spatially, the occurrence of imported cases by census tract was mildly associated with a higher proportion of foreign population and more people at active age, while occurrence of autochthonous cases was not significantly associated with any of the studied *** census tracts with laboratory confirmed results, the models showed higher probability of autochthonous cases related to higher population density and population age structure. The clustering of autochthonous cases was generally mild, with prevailing i

关键词： Aedes aegypti Vector-borne diseases Vector control Dengue epidemic

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Contemporary climate infuence on variability patterns of Anadenanthera colubrina ***,a key species in seasonally dry tropical forests

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Journal of Forestry research 2022年第1期33卷 89-101页

作者： maría Victoria García maría Eugenia Barrandeguy Kathleen Prinz Genética de Poblaciones y Cuantitativa-Departamento de Genética-Facultad de Ciencias Exactas Químicas y Naturales-Universidad Nacional deMisionesInstituto de Biología Subtropical(UNaM-CONICET)Nodo PosadasFélix de Azara 15523300 PosadasArgentina Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET) PosadasMisionesArgentina Institute of Systematic Botany With Herbarium Haussknecht and Botanical Gardens Friedrich-Schiller-University Jena07743 JenaGermany

The distribution of many plant species has been shaped by climate changes,and their current phenotypic and genetic variability refect microclimatically suitable *** study relates contemporary climate to variability patterns of phenotypic traits and molecular markers in the Argentinean distribution of Anadenanthera colubrina ***,as well as to identify the most relevant phenotypic trait or molecular marker associated with those *** from four populations in both biogeographic provinces,Paranaense and yungas,were *** analyses and multiple linear regressions were carried out to determine relationships among phenotypic traits and nuclear microsatellites,respectively,to climatic variables,and to identify the phenotypic traits as well as nuclear microsatellite loci most sensitive to *** and three clusters of individuals were detected based on genetic and phenotypic data,*** clusters based on genetic data refected the biogeographic origin of *** traits were the most relevant indicators of climatic *** microsatellite locus Ac41.1 appeared to be non-neutral presenting a strong correlation with climate variable temperature *** findings show complex patterns of genetic and phenotypic variability in the Argentinean distribution of *** *** related to the present or contemporary climate,and provides an example for an integrative approach to better understand climate impact on contemporary genetic and phenotypic variability in light of global climate change.

关键词： Contemporary climate Curupay Genetic variability Phenotypic variability Seasonally dry tropical forests

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Challenges and improvement strategies in the hospitalization of chronic multimorbid patients

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World Journal of Clinical Cases 2025年第3期13卷 35-41页

作者： Andres Fontalba-Navas Francisco Pozo Muñoz rogelio Garcia Cisneros maria Jose Garcia Larrosa maria del mar Callejon Gil Ignacio Garcia Delgado maria Belen Jimenez martinez Antequera Hospital Northern Málaga Integrated Healthcare AreaAntequera 29200AndalusiaSpain Department of Public Health and Psychiatry University of MálagaMálaga 29010Spain Antequera Hospital Northern Málaga Antequera Integrated Healthcare AreaAntequera 29200MálagaSpain

BACKGrOUND Addressing the growing challenge of hospitalizing chronic multimorbid patients,this study examines the strain these conditions impose on healthcare systems at a local level,focusing on a pilot *** diseases and complex patients require comprehensive management strategies to reduce healthcare burdens and improve patient *** proven effective,this pilot model has the potential to be replicated in other healthcare settings to enhance the management of chronic multimorbid *** To evaluate the effectiveness of the high complexity unit(HCU)in managing chronic multimorbid patients through a multidisciplinary care model and to compare it with standard hospital *** The study employed a descriptive longitudinal approach,analyzing data from the Basic Minimum Data Set(BMDS)to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout *** HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity *** The study employed a descriptive longitudinal approach,analyzing data from the BMDS to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout *** HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity *** This study demonstrates the effectiveness of the HCU in managing patients with complex chronic diseases through a multidisciplinary *** coordinated care provided by the HCU results in improved patient outcomes,reduced unnecessary hospitalizations,and better management of patient *** superiority of the HCU compared to standard care is evident in key outcomes such as fewer readmissions and higher patient satisfaction,reinforcing its value as a model of ca

关键词： High complexity unit Chronic multimorbidity Patient-centered care Integrated care Healthcare management

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