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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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Kinetics of the reaction of OH radical with ethylfluoroacetate,ethyl 4,4,4-trifluorobutyrate,and butylfluoroacetate

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Journal of Environmental Sciences 2025年第5期151卷 273-283页

作者： Pedro L.Lugo Vianni Straccia mariano A.Teruel maría B.Blanco Laboratorio Universitario de Química y Contaminación del Aire(L.U.Q.C.A) Institute for Research in Physical Chemistry of Córdoba(I.N.F.I.Q.C.)Department of Physical ChemistryFaculty of Chemical SciencesNational University of CórdobaUniversity CityCórdoba 5000Argentina institute for Atmospheric and Environmental Research University of WuppertalWuppertal DE-42097Germany

Kinetics of the gas-phase reactions of•OH radicals with a series of fluoroesters were studied for the first time at 298±3 K and atmospheric *** rate coefficients were determined by in situ FTIR spectroscopy in nitrogen and GC-FID in air to monitor the decay of reactants and *** following coefficient values(in 10^(−12)cm^(3)/(molecule•sec))were obtained for ethyl fluoroacetate(EFA),ethyl 4,4,4-trifluorobutyrate(ETB),and butyl fluoroacetate(BFA),respectively:k_(1)(EFA+OH)=1.15±0.25 by FTIR and 1.34±0.23 by GC-FID;k_(2)(ETB+OH)=1.61±0.36 by FTIR and 2.02±0.30 by GC-FID;k_(3)(BFA+OH)=2.24±0.37 by *** trends were developed and correlated with the number of CH_(3)and F substituents in the fluoroester,and structure-activity relationships(SARs)calculations were *** addition,the tropospheric lifetimes of EFA,ETB,and BFA upon degradation by OH radicals were calculated to be 9,6,and 5 days,respectively,indicating that these fluorinated compounds could have a possible regional effect from the emission *** small photochemical ozone creation potentials of 9,7,and 19 were estimated for EFA,ETB,and BFA,*** GlobalWarming Potentials(GWPs)for EFA,ETB,and BFA were calculated for different time *** a 20-year time horizon,the GWPs were 1.393,0.063,and 0.062,*** the case of a 100-year time horizon,the GWPs were 0.379,0.017,and 0.017,and for a 500-year time horizon,the GWPs were 0.108,0.005,and 0.005 for EFA,ETB,and BFA.

关键词： CFC replacements sinks in situ FTIR SAR Acidification potentials Greenhouse gases

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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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Atmospheric chemistry of trifluorodicarbonyls initiated by Cl atoms:Reactivity trends,mechanism,and acid formation yields

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Journal of Environmental Sciences 2025年第5期151卷 12-25页

作者： Pedro L.Lugo Vianni G.Straccia Cynthia B.Rivela mariano A.Teruel maría B.Blanco Laboratorio Universitario de Química y Contaminación del Aire(L.U.Q.C.A) Instituto de Investigaciones en Fisicoquímica de Córdoba(I.N.F.I.Q.C.)Dpto.de Fisicoquímica.Facultad de Ciencias QuímicasUniversidad Nacional de Córdoba.Ciudad Universitaria5000 CórdobaArgentina institute for Atmospheric and Environmental Research University of WuppertalDE-42097 WuppertalGermany

Rate coefficients of the gas-phase reactions of Cl atoms with a series of fluorinated diketones(FDKs):CF_(3)C(O)CH_(2)C(O)CH_(3)(TFP),CF_(3)C(O)CH_(2)C(O)CH_(2)CH_(3)(TFH)and CF_(3)C(O)CH_(2)C(O)CH(CH_(3))2(TFMH),have been measured at(298±2)K and under atmospheric *** experiments were performed using the relative-rate method with a GC-FID detection *** different determinations and references used,the following rate coefficients were obtained(in cm3/(molecule·sec)):k_(4)(TFP+Cl)=(1.75±0.21)×10^(−10),k_(5)(TFH+Cl)=(2.05±0.23)×10^(−10),k_(6)(TFMH+Cl)=(2.71±0.34)×10^(−10).Reactivity trends of FDKs were discussed and Free Energy Relationships analysis was *** expression lgkOH=1.68 lgkCl+5.71 was obtained for the reactivity of the studied FDKs together with similar unsaturated VOCs with Cl and OH radicals Additionally,acetic acid(CH_(3)C(O)OH)and trifluoroacetic acid(CF_(3)C(O)OH)were positively identified and quantified as degradation products using in situ FTIR *** to the identified products,atmospheric chemical mechanisms were *** atmospheric implications of the studied reactions were assessed by the estimation of the tropospheric lifetimes of TFP,TFH,and TFMH concerning their reaction with Cl atoms to be 48,41,and 31 hours,*** relatively short residence in the atmosphere of the fluorocarbons studied will have a local/regional impact with restricted *** warming potential(GWP(20 yr))calculated for the studied fluoro diketones were 0.014,0.003 and 0.001 for TFP,TFH and TFMH,respectively with a negligible contribution to the greenhouse effect.

关键词： Fluorinated diketones Kinetics SPME-GC-FID FTIR in situ SAR Free energy relationships

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Agronomic treatments combined with embryo rescue for rapid generation advancement in tomato speed breeding

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Horticultural Plant Journal 2025年第1期11卷 239-250页

作者： Esther Gimeno-Paez Jaime Prohens maria Moreno-Cervero Ana de Luis-margarit maria Jose Diez Pietro Gramazio Escuela de Doctorado Universidad Catolica de Valencia San Vicente MartirGuillem de Castro 9446001 ValenciaSpain instituto de Conservaciony Mejora dela Agrodiversidad Valenciana Universitat Politecnica de ValenciaCamino de Vera 1446022 ValenciaSpain Departamento de Ciencias Experimentales y Matematicas Facultad de Veterinaria y Ciencias ExperimentalesUniversidad Catolica de Valencia San Vicente MartirGuillem de Castro 9446001 ValenciaSpain

Unlike other major crops,little research has been performed on tomato to reduce the generation time for speed *** evaluated several agronomic treatments to reduce the generation time of tomato in the‘M82'(determinate)and‘Moneymaker'(indeterminate)varieties and evaluated the best combination in conjunction with embryo *** container sizes with volumes of 0.2 L(XS),0.45 L(S),0.8 L(M),1.3 L(L),and6 L(XL),were evaluated in the first experiment under the autumn *** found that plants grown in XL containers exhibited better development and required less time from sowing to anthesis(DSA)and from anthesis to fruit ripening(DAR).In the second experiment,using XL containers in the autumn-winter cycle,we evaluated the effects of cold priming at the cotyledonary stage,water stress,P supplementation,and K supplementation on generation *** to the control,we found that cold priming significantly reduced the number of leaves,plant height to first the inflorescence,and DSA(2.7 d),whereas K supplementation reduced the DAR(8.8 d).In contrast,water stress and P supplementation did not significantly affect any of the measured traits like DAR,DSA or fruit *** validate these data,in a third experiment with XL containers in the spring-summer cycle,the combination of cold priming and K supplementation was tested,confirming the significant effect of this combination on the reduction of generation time(2.9 d for DSA and 3.9 d for DAR)compared to the *** rescue during the cell expansion cycle(average of 22.0 d and 23.3 d after anthesis for‘M82'and‘Moneymaker',respectively)allowed the shortening of the generation time by 8.7 d in‘M82'and 11.6 d in‘Moneymaker'compared to the in planta fruit *** combination of agronomic treatments with embryo rescue can effectively increase the number of generations per year from three to four for speed breeding of tomato.

关键词： Solanum lycopersicum Generation time Speed breeding Container size Cold priming K supplementation Embryo rescue

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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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Prognosis in stage II colon cancer:Expanding the horizons of risk factors

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 28-34页

作者： maría Belén Novoa Díaz Claudia Gentili maría Julia martín Pedro Carriere Department of Biología Bioquímica y FarmaciaUniversidad Nacional del Sur(UNS)-INBIOSUR(CONICET-UNS)Bahía Blanca 8000Buenos AiresArgentina Department of Biología Bioquímica y FarmaciaUniversidad Nacional del Sur(UNS)-INIBIBB(CONICET-UNS)Bahía Blanca 8000Buenos AiresArgentina

we critically review the authors’perspective and analyze the relevance of the results obtained in the original article of clinical research by Liu et *** consider that additional factors associated with colon cancer progression have recently been described in extensive clinical research,and should be included in this analysis to achieve a more accurate *** factors include inflammation,gut microbiota composition,immune status and nutritional balance,as they influence the post-surgical survival profile of patients with stage II colorectal *** also address the clinical implementation and limitations of these *** of the patient´s entire context is essential for selection of the most appropriate therapy.

关键词： Risk factor Prognosis Colon cancer Inflammation markers Tumor location

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