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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 mar.a Fernanda González Ana mar.a 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： mar.a 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： mar.a Norte-Muñoz mar.a Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega mar Pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz mar.a Teresa Moreno-Flores mar.a 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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Oxidative stress,the blood-brain barrier and neurodegenerative diseases:The critical beneficial role of dietary antioxidants

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Acta Pharmaceutica Sinica B 2023年第10期13卷 3988-4024页

作者： Jin Feng Youle Zheng Mingyue Guo Irma Ares mar.a martínez Bernardo Lopez-Torres mar.a-Rosa martínez-Larran aga Xu Wang Arturo Anadon mar.a-aranzazu martínez National Reference Laboratory of Veterinary Drug Residues(HZAU)and MAO Key Laboratory for Detection of Veterinary Drug Residues Huazhong Agricultural UniversityWuhan 430070China MAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products Huazhong Agricultural UniversityWuhan 430070China Department of Pharmacology and Toxicology Faculty of Veterinary MedicineUniversidad Complutense de Madrid(UCM)And Research Institute Hospital 12 de Octubre(i+12)Madrid 28040Spain

In recent years,growing awareness of the role of oxidative stress in brain health has prompted antioxidants,especially dietary antioxidants,to receive growing attention as possible treatments strategies for patients with neurodegenerative diseases(NDs).The most widely studied dietary antioxidants include active substances such as vitamins,carotenoids,flavonoids and *** antioxidants are found in usually consumed foods such as fresh fruits,vegetables,nuts and oils and are gaining popularity due to recently growing awareness of their potential for preventive and protective agents against NDs,as well as their abundant natural sources,generally non-toxic nature,and ease of long-term *** review article examines the role of oxidative stress in the development of NDs,explores the‘two-sidedness’of the blood-brain barrier(BBB)as a protective barrier to the nervous system and an impeding barrier to the use of antioxidants as drug medicinal products and/or dietary antioxidants supplements for prevention and therapy and reviews the BBB permeability of common dietary antioxidant suplements and their potential efficacy in the prevention and treatment of ***,current challenges and future directions for the prevention and treatment of NDs using dietary antioxidants are discussed,and useful information on the prevention and treatment of NDs is provided.

关键词： Dietary antioxidant supplements Oxidative stress Blood-brain barrier Neurodegenerative diseases Vitamins Carotenoids Flavonoids Polyphenols

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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 mar.a JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri mar.a 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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Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

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Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： Danko Jeremic Lydia Jiménez-Díaz Juan D.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

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5DGWO-GAN:A Novel Five-Dimensional Gray Wolf Optimizer for Generative Adversarial Network-Enabled Intrusion Detection in IoT Systems

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Computers, Materials & Continua 2025年第1期82卷 881-911页

作者： Sarvenaz Sadat Khatami Mehrdad Shoeibi Anita Ershadi Oskouei Diego martín maral Keramat Dashliboroun Department of Data Science Engineering University of HoustonHoustonTX 77204USA The WPI Business School Worcester Polytechnic InstituteWorcesterMA 01609USA School of Systems and Enterprises Stevens Institute of TechnologyHobokenNJ 07030USA Department of Computer Science Escuela de Ingeniería Informática de SegoviaUniversidad de ValladolidSegovia40005Spain Ernest G.Welch School of Art&Design Georgia State UniversityAtlantaGA 30303USA

The Internet of Things(IoT)is integral to modern infrastructure,enabling connectivity among a wide range of devices from home automation to industrial control *** the exponential increase in data generated by these interconnected devices,robust anomaly detection mechanisms are *** detection in this dynamic environment necessitates methods that can accurately distinguish between normal and anomalous behavior by learning intricate *** paper presents a novel approach utilizing generative adversarial networks(GANs)for anomaly detection in IoT ***,optimizing GANs involves tuning hyper-parameters such as learning rate,batch size,and optimization algorithms,which can be challenging due to the non-convex nature of GAN loss *** address this,we propose a five-dimensional Gray wolf optimizer(5DGWO)to optimize GAN *** 5DGWO introduces two new types of wolves:gamma(γ)for improved exploitation and convergence,and theta(θ)for enhanced exploration and escaping local *** proposed system framework comprises four key stages:1)preprocessing,2)generative model training,3)autoencoder(AE)training,and 4)predictive model *** generative models are utilized to assist the AE training,and the final predictive models(including convolutional neural network(CNN),deep belief network(DBN),recurrent neural network(RNN),random forest(RF),and extreme gradient boosting(XGBoost))are trained using the generated data and AE-encoded *** evaluated the system on three benchmark datasets:NSL-KDD,UNSW-NB15,and *** conducted on diverse IoT datasets show that our method outperforms existing anomaly detection strategies and significantly reduces false *** 5DGWO-GAN-CNNAE exhibits superior performance in various metrics,including accuracy,recall,precision,root mean square error(RMSE),and convergence *** proposed 5DGWO-GAN-CNNAE achieved the lowest RMSE values across the NSL-KDD,UNSW-NB15,and

关键词： Internet of things intrusion detection generative adversarial networks five-dimensional binary gray wolf optimizer deep learning

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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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Characterization and QTL identification in eggplant introgression lines under two N fertilization levels

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Horticultural Plant Journal 2023年第5期9卷 971-985页

作者： Elena Rosa-martínez Gloria Villanueva Ahmet Sahin Pietro Gramazio mar.a Dolores García-martínez mar.a Dolores Raig on Santiago Vilanova Jaime Prohens mariola Plazas Instituto de Conservacion y Mejora de la Agrodiversidad Valenciana Universitat Politecnica de ValenciaCamino de Vera 1446022 ValenciaSpain Instituto de Biología Molecular y Celular de Plantas Consejo Superior de Investigaciones Científicas-Universitat Politecnica de ValenciaCamino de Vera 1446022 ValenciaSpain

Lowering nitrogen inputs is a major goal for sustainable *** the present study,a set of 10 Solanum melongena introgression lines(ILs)developed using Solanum incanum as the exotic donor parent were grown under two nitrogen fertilization doses supplied with the irrigation system:1)8.25 mmol·L-1NH4NO3,corresponding to the high nitrogen treatment(HN),and 2)no external nitrogen supply,corresponding to the low nitrogen treatment(LN).Twenty traits,including plant growth and yield parameters,fruit size and morphology,nitrogen and carbon content in leaf and fruit,and phenolics content in fruit,were *** aim was to select of potential materials for eggplant breeding under low N inputs,as well as to identify and locate putative QTLs associated with the traits *** significant differences were observed between the soil characteristics of the HN and LN treatments,except for nitrogen and iron content,which was slightly lower in the HN,probably as a consequence of higher nutrient removal from soil by plants in the latter *** of variance showed that lowering nitrogen inputs did not significantly affect the final yield,fruit morphology,size and phenolics *** agronomic traits were highly and positively correlated with each other under both treatments,as well as total phenolics with chlorogenic acid *** assessment of the differences between each IL and the recipient parent resulted in the identification of 36 QTLs associated with most of the traits—12 were specific to the HN,17 specific to the LN,and 7 were stable across *** introgressed fragment of *** generally had a negative effect on the trait,except for QTLs for fruit dry matter,for fruit length on chromosome 10 under the HN,and for fruit pedicel length on chromosome 9 under the *** increase over AN-S-26 of the allele of *** for the QTLs detected ranged between-73.98% and 26.03% in HN and-73.67%and 34.43% in *** findings provide useful tools fo

关键词： Solanum melongena Solanum incanum Wild relatives N fertilization Abiotic stress QTL

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