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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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Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease:A crosssectional study

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World Journal of Gastroenterology 2025年第7期31卷 63-73页

作者： Yolanda Real Martinez Carlos Ernesto Fernandez-Garcia Esther Fuertes-Yebra Mario Calvo Soto Angela Berlana Vicente Barrios Maria Caldas Leticia Gonzalez Moreno Luisa Garcia-Buey Begoña Molina Baena Miguel Sampedro-Nuñez Maria J Beceiro C García-Monzón Águeda González-Rodríguez Servicio Aparato Digestivo Hospital Universitario La PrincesaInstituto de Investigación Sanitaria La PrincesaUniversidad Autónoma de MadridMadrid 28006Spain Unidad de Investigación Hospital Universitario Santa CristinaInstituto de Investigación Sanitaria La PrincesaMadrid 28009Spain Department of endocrinology Department of PediatricsHospital Infantil Universitario Niño JesúsInstituto de Investigación La PrincesaMadrid 28009Spain Centro de Investigación biomédica en Red de Fisiopatología de la Obesidad y Nutrición Instituto de Salud Carlos IIIMadrid 28029Spain Servicio de endocrinología y Nutrición Hospital Universitario La PrincesaInstituto de Investigación Sanitaria La PrincesaUniversidad Autónoma de MadridMadrid 28006Spain Instituto de Investigaciones biomédicas Sols-Morreale(IIBM) CSIC-UAMMadrid 28029Spain Centro de Investigación biomédica en Red de Diabetes y enfermedades Metabólicas Asociadas Madrid 28029Spain

BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these ***,their actual prevalence and pathophysiology remain to be *** To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with *** Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level *** degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional *** and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD *** analysis was performed comparing results according to liver fibrosis and *** No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver ***,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD *** serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.

关键词： Skeletal muscle alterations Myokines Metabolic dysfunction-associated steatotic liver disease Liver fibrosis Hepatosteatosis

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Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： Marta García-Juan Mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación biomédica en Red de enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

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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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Glial-derived transforming growth factor β1(TGF-β1):a key factor in multiple sclerosis neuroinflammation

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Neural Regeneration Research 2021年第3期16卷 510-511页

作者： Coram Guevara Fernando C.Ortiz Mechanisms of Myelin Formation and Repair Laboratory Instituto de Ciencias BiomédicasFacultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Glial cell activation and neuroinflammation in multiple sclerosis(MS):MS is an irreversible and progressive central nervous system(CNS)disease which originates in the autoimmune attack of lymphocytes against CNS *** specialized membrane,synthesized by oligodendrocytes(OL)in the CNS,provides metabolic support to axons and allows for saltatory conduction in *** lack of myelin(i.e.,demyelination)leads to axonal degeneration,neuronal death,and the consequent neurological disabilities(Franklin and Ffrench-Constant,2017).

关键词： inflammation degeneration sclerosis

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Are urbanization,biotic and social factors associated with the song frequency and song entropy attributes of three urban syntopic passerines?

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Avian Research 2025年第1期16卷 96-109页

作者： Xhareni Díaz-Lezama Alejandro Ariel Ríos-Chelén Jorge Castellanos-Albores Paula Lenríquez Programa de Posgrado en ciencias en Recursos Naturales y Desarrollo Rural El Colegio de la Frontera Sur.Carr.Panamericana y Periférico Sur s/n Barrio Ma.Auxiliadora29290.San Cristóbal de Las CasasChiapasMexico Centro Tlaxcala de Biología de la Conducta Universidad Autónoma de TlaxcalaUniversidad 1La Loma XicohtencatlCentro90000TlaxcalaMexico Departamento Conservación de la Biodiversidad El Colegio de la Frontera SurCarr.Panamericana y Periférico Sur s/n Barrio Ma.Auxiliadora29290 San Cristóbal de Las CasasChiapasMexico

Urban environments have challenging characteristics for bird acoustic *** levels of anthropogenic noise,as well as vegetation structure(e.g.,in urban parks),can potentially affect the song frequency characteristics of several bird *** additional factor such as the abundance of conspecific and heterospecific vocalizing birds may play an important role in determining the structure of bird *** this study,we analyzed whether noise levels,vegetation percentage,and abundance of conspecifics and heterospecifics influence the song characteristics of three syntopic songbird species:House Finch(Haemorhous mexicanus),Rufouscollared Sparrow(Zonotrichia capensis),and House Sparrow(Passer domesticus)living in urban *** recorded songs of these species and measured the peak frequency and entropy of their songs at 14 sites in the city of San Cristobal de Las Casas,Chiapas,*** found that the song peak frequency of House Finch and House Sparrow's songs was negatively related to the *** peak frequency of neither of the three species correlated with the average noise ***,the abundances of conspecific and heterospecific were related to the peak frequency of the three species'*** entropy of the House Finch and House Sparrow songs was positively and negatively related,respectively,to noise *** Sparrow song entropy was negatively related to the percentage of *** entropy of House Finches was negatively associated to conspecific and House Sparrow *** entropy of Rufous-collared Sparrows was positively related to conspecific *** conclusion,the song peak frequency and song entropy of the three songbird species were differentially related to urban noise,vegetation,and conspecific and heterospecific abundance,suggesting these factors influence bird song characteristics.

关键词： Bird song Noise Song entropy Song peak frequency Vegetation

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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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The use of fibroblasts as a valuable strategy for studying mitochondrial impairment in neurological disorders

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Translational Neurodegeneration 2022年第1期11卷 401-425页

作者： Margrethe A.Olesen Francisca Villavicencio-Tejo Rodrigo A.Quintanilla Laboratory of Neurodegenerative Diseases Facultad de Ciencias de La SaludInstituto de Ciencias BiomédicasUniversidad Autónoma de ChileSantiagoChile

Neurological disorders(NDs)are characterized by progressive neuronal dysfunction leading to synaptic failure,cognitive impairment,and motor *** these diseases,Alzheimer’s disease(AD),Parkinson’s disease(PD),Huntington’s disease(HD),and amyotrophic lateral sclerosis(ALS)have raised a significant research *** disorders present common neuropathological signs,including neuronal dysfunction,protein accumulation,oxidative damage,and mitochondrial *** this context,mitochondrial impairment is characterized by a deficiency in ATP production,excessive production of reactive oxygen species,calcium dysregulation,mitochondrial transport failure,and mitochondrial dynamics *** defects in mitochondrial health could compromise the synaptic process,leading to early cognitive dysfunction observed in these ***,skin fibroblasts from AD,PD,HD,and ALS patients have been suggested as a useful strategy to investigate and detect early mitochondrial abnormalities in these *** this context,fibroblasts are considered a viable model for studying neurodegenerative changes due to their metabolic and biochemical relationships with ***,studies of our group and others have shown impairment of mitochondrial bioenergetics in fibroblasts from patients diagnosed with sporadic and genetic forms of AD,PD,HD,and ***,these mitochondrial abnormalities have been observed in the brain tissues of patients suffering from the same ***,fibroblasts represent a novel strategy to study the genesis and progression of mitochondrial dysfunction in AD,PD,HD,and *** review discusses recent evidence that proposes fibroblasts as a potential target to study mitochondrial bioenergetics impairment in neurological disorders and consequently to search for new biomarkers of neurodegeneration.

关键词： Mitochondria Fibroblasts Cell reprogramming Alzheimer’s disease Parkinson’s disease Huntington’s disease Amyotrophic lateral sclerosis Mitochondrial dysfunction

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ApoB-100, ApoE and CYP7A1 gene polymorphisms in Mexican patients with cholesterol gallstone disease

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World Journal of Gastroenterology 2010年第37期16卷 4685-4690页

作者： Sánchez-Cuén Jaime Aguilar-Medina Maribel Arámbula-Meraz Eliakym Romero-Navarro José Granados Julio Sicairos-Medina Laura Ramos-Payán Rosalío División de Gastroenterología Hospital Regional ISSSTE Facultad de ciencias Químico Biológicas Doctorado en Biotecnología y Maestría en Ciencias Biomédicas Universidad Autónoma de Sinaloa División de Inmunogenética Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

AIM: To determine the possible association of the ApoB100 (Xba Ⅰ ), ApoE (Hha Ⅰ ) and CYP7A1 (Bsa Ⅰ ) gene polymorphisms, with the development of cholesterol gallstone disease (GD) in a Mexican population. METHODS: The polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by ethnicity, age and sex: patients with GD (n = 101) and stone-free control subjects (n = 101). RESULTS: Allelic frequencies in patients and controls were: 34.16% vs 41.58% (P = 0.124) for X+of ApoB-100; 4.46% vs 5.94% (P = 0.501) for E2, 85.64% vs 78.22% (P = 0.052) for E3, 9.90% vs 15.84% (P = 0.075) for E4 of ApoE; and 25.74% vs 27.72% (P = 0.653) for C of CYP7A1. Differences in genotypic frequencies between the studied groups were not significant (P en the studied polymorphisms and cholelithiasis in this high prevalent population.

关键词： Apolipoprotein CYP7A1 Gallstones Mexicans Polymorphisms

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Effect of aging on behaviour of mesenchymal stem cells

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World Journal of Stem Cells 2019年第6期11卷 337-346页

作者： Juan Antonio Fafián-Labora Miriam Morente-López María C Arufe Grupo de Terapia Celular y Medicina Regenerativa Departamento de Fisioterapia Ciencias Biomédicas y MedicinaUniversidade da Coru?a

Organs whose source is the mesoderm lineage contain a subpopulation of stem cells that are able to differentiate among mesodermal derivatives (chondrocytes, osteocytes, adipocytes). This subpopulation of adult stem cells, called “mesenchymal stem cells” or “mesenchymal stromal cells (MSCs)”, contributes directly to the homeostatic maintenance of their organs;hence, their senescence could be very deleterious for human bodily functions. MSCs are easily isolated and amenable their expansion in vitro because of the research demanding to test them in many diverse clinical indications. All of these works are shown by the rapidly expanding literature that includes many in vivo animal models. We do not have an in-depth understanding of mechanisms that induce cellular senescence, and to further clarify the consequences of the senescence process in MSCs, some hints may be derived from the study of cellular behaviour in vivo and in vitro, autophagy, mitochondrial stress and exosomal activity. In this particular work, we decided to review these biological features in the literature on MSC senescence over the last three years.

关键词： Mesenchymal stem cells Aging Autophagy Mitochondrial stress Extracellular vesicles

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