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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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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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Antioxidant role of heme oxygenase-1 in prehepatic portal hypertensive rats

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World Journal of Gastroenterology 2006年第26期12卷 4149-4155页

作者： Soledad Gonzales mar.a Julia Pérez Juan C Perazzo mar.a luján tomaro Department of Biological Chemistry School of Pharmacy and Biochemistry University of Buenos AiresBuenos Aires 1113Argentina Laboratory of Portal Hypertension Department of Biological Science School of Pharmacy and BiochemistryUniversity of Buenos AiresBuenos Aires 1113Argentina

AIM： To study the effect of bilirubin on the oxidative liver status and the activity and expression of heine oxygenase-1 （HO-1） in rat liver injury induced by prehepatic portal hypertension. METHODS： Wistar male rats, weighing 200-250 g, were divided at random into two groups： one group with prehepatic portal hypertension （PH） induced by regulated prehepatic portal vein ligation （PPVL） and the other group corresponded to sham operated rats. Portal pressure, oxidative stress parameters, antioxidant enzymes, HO-1 activity and expression and hepatic sinusoidal vasodilatation were measured. RESULTS： In PPVL rats oxidative stress was evidenced by a marked increase in thiobarbituric acid reactive substances （TBARS） content and a decrease in reduced glutathione （GSH） levels. The activities of liver antioxidant enzymes, superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GSH-Px） were also diminished while activity and expression of HO-1 were enhanced. Administration of bilirubin （5μmol/kg body weight） 24 h before the end of the experiment entirely prevented all these effects. Pretreatment with Sn-protoporphyrin IX （Sn-PPIX）（100 μg/kg body weight, i.p.）, a potent inhibitor of HO, completely abolished the oxidative stress and provoked a slight decrease in liver GSH levels as well as an increase in lipid peroxidation. Besides, carbon monoxide, another heme catabolic product, induced a significant increase in sinusoidal hepatic areas in PPVL group. Pretreatment of PPVL rats with Sn-PPIX totally prevented this effect COnCLUSIOn： These results suggest a beneficial role of HO-1 overexpression in prehepatic portal hypertensive rats.

关键词： Heme oxygenase-1 Portal hypertensive rats Liver oxidative stress

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Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

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World Journal of Gastroenterology 2009年第23期15卷 2893-2899页

作者： Gabriela Beatriz Acosta mar.a Alejandra Fernández Diego martín Roselló mar.a luján tomaro Karina Balestrasse Abraham Lemberg Institute of Pharmacological Research (InInFA) National Research Council of Argentina (CONICET) and University of Buenos Aires Junín 956. 5th floor C1113AAD Buenos Aires Argentina Laboratory of Portal Hypertension School of Pharmacy and Biochemistry University of Buenos Aires Junín 956. 5th floor C1113AAD Buenos Aires Argentina Department of Biological Chemistry School of Pharmacy and Biochemistry University of Buenos Aires Junín 596. 5th floor C1113AAD Buenos Aires Argentina

AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into shamoperated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, signif icantly and persistent increase in this excitatory neurotransmitter activity. COnCLUSIOn: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modif ies the normal function in some brain regions.

关键词： Portal hypertension Glutamine synthetase Glutamate uptake Frontal cerebral cortex Hippocampus Rat

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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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Glutamine is highly effective in preventing in vivo cobalt-induced oxidative stress in rat liver

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World Journal of Gastroenterology 2005年第23期11卷 3533-3538页

作者： Soledad Gonzales Ariel H.Polizio mar.a A.Erario mar.a L.tomaro Departamento de Química Biológica

AIM: To evaluate the in vivo effect of glutamine on cobaltgenerated oxidative stress and (HO-1) induction in rat ***: Fasted female Wistar rats received a single injection of cobalt chloride (375 μmol/kg body weight) and then were killed at different times. Lipid peroxidation and soluble and enzymatic antioxidant defense system (reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) were measured in liver homogenates. Ferritin and ferritin iron contents as well as heme oxygenase-1 (HO-1) activity and expression were also determined. The antioxidant properties of glutamine (Gin) were also evaluated. RESULTS: Cobalt chloride increased lipid peroxidation (50% over control values) 1 h after treatment. GSH reached a minimum at 3 h (40%) increasing thereafter. Twelve hours after CoCl2 injection, the antioxidant enzymes CAT, GSH-Px and SOD also diminished by about 30%. Heme oxygenase-1 induction was observed 6 h after treatment reaching a maximum value of 14-fold over the controls, 12 h after cobalt treatment. A 1.7-fold increase in ferritin and ferritin-bound iron 24 h after treatment were also obtained. Administration of glutamine (300 mg/kg body weight) by gavage 24 h before CoCl2 treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels, and partially reverted heme oxygenase-1 induction. COnCLUSIOn: These results suggested that a natural product such as glutamine prevents glutathione depletion and consequently heme oxygenase induction.

关键词： Oxidative stress Heme oxygenase Glutathione Glutamine Iron Liver

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Impact of protein-providing milk ingredients on volatile compounds,microstructure,microbiology and physicochemical characteristics of yogurts

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Food Bioscience 2023年第3期53卷 1044-1050页

作者： Claudia Inés Vénica Irma Verónica Wolf mar.a Julia Spotti mar.a luján Capra Diego Javier Mercanti mar.a Cristina Perotti Instituto de Lactología Industrial(InLAIn) Universidad Nacional del Litoral(UNL)/Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Facultad de Ingeniería Química(FIQ)Santiago del Estero 2829S3000AOMSanta FeArgentina Instituto de Tecnología de Alimentos(ITA) FIQUNLSantiago del Estero 2829S3000AOMSanta FeArgentina

The impact of skim milk(SM),demineralized whey(DW),whey protein concentrate(WPC40-WPC80),isolated(WPI)and hydrolyzed(WPH)on different parameters of yogurts have been evaluated using SLB95 and Yoflex *** of whey proteins shortened the fermentation time in yogurts with the exception of WPH,which extended it and presented the highest titratable *** increased the Lactobacillus and decreased Streptococcus population in yogurts with SLB95 *** and WPC80 increased water-holding *** and WPC80 yogurts exhibited larger aggregates,compared to the rest ingredients,and be bigger with the SLB95 *** volatile compounds differ,though not greatly,among yogurts.

关键词： Fermented milks Milk proteins Flavor compounds Microscopy images Microbial counts Quality properties

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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 mar.a 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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