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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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Contribution of the Open Access Modality to the Impact of Hybrid Journals Controlling by Field and Time Effects

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Journal of Data and Information Science 2022年第2期7卷 57-83页

作者： Pablo Dorta-gonzález maría Isabel Dorta-gonzález University of Las Palmas de Gran Canaria TiDES Research Institute35017 Las Palmas de Gran CanariaSpain University of La Laguna 38271 La LagunaSpain

Purpose:Researchers are more likely to read and cite papers to which they have access than those that they cannot ***,the objective of this work is to analyze the contribution of the Open Access(OA)modality to the impact of hybrid ***/methodology/approach:The“research articles”in the year 2017 from 200 hybrid journals in four subject areas,and the citations received by such articles in the period 2017-2020 in the Scopus database,were *** hybrid OA papers were compared with the paywalled *** journals were randomly selected from those with share of OA papers higher than some minimal *** than 60 thousand research articles were analyzed in the sample,of which 24%under the OA ***:We obtain at journal level that cites per article in both hybrid modalities(OA and paywalled)strongly ***,there is no correlation between the OA prevalence and cites per *** is OA citation advantage in 80%of hybrid ***,the OA citation advantage is consistent across fields and held in *** obtain an OA citation advantage of 50%in average,and higher than 37%in half of the hybrid ***,the OA citation advantage is higher in Humanities than in Science and Social *** limitations:Some of the citation advantage is likely due to more access allows more people to read and hence cite articles they otherwise would ***,causation is difficult to establish and there are many possible *** factors can affect the observed differences in citation *** mandates can be one of *** are likely to have OA requirement,and well-funded studies are more likely to receive more citations than poorly funded *** discussed factor is the selection bias postulate,which suggests that authors choose only their most impactful studies to be open *** implications:For hybrid journals,the open access modality is positive,in the sense that it provides a greater

关键词： Open access Open science Scholarly communication Hybrid journals Citation advantage

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Existence and Uniqueness to a Fully Nonlinear Version of the Loewner–Nirenberg Problem Dedicated to Celebrate the Sixtieth Anniversary of USTC

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Communications in Mathematics and Statistics 2018年第3期6卷 269-288页

作者： maría del mar gonzález YanYan Li Luc Nguyen Departamento de Matemáticas Universidad Autónoma de MadridCampus de Cantoblanco28049 MadridSpain Department of Mathematics Hill CenterBusch CampusRutgers University110 Frelinghuysen RoadPiscatawayNJ 08854USA Mathematical Institute and St Edmund Hall University of OxfordAndrew Wiles BuildingRadcliffe Observatory QuarterWoodstock RoadOxford OX26GGUK

We consider the problem of finding on a given Euclidean domainof dimension n≥3 a complete conformally flat metric whose Schouten curvature A satisfies some equations of the form f(λ(−A))=*** generalizes a problem considered by Loewner and Nirenberg for the scalar *** prove the existence and uniqueness of such metric when the boundary δΩ is a smooth bounded hypersurface(of codimension one).When δΩ contains a compact smooth submanifold ∑ of higher codimension with δΩ\∑ being compact,we also give a‘sharp’condition for the divergence to infinity of the conformal factor near ∑ in terms of the codimension.

关键词： Fully nonlinear Loewner-Nirenberg problem Singular fully nonlinear Yamabe metrics Conformal invariance

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Crosslinked hyaluronic acid with liposomes and crocin for management symptoms of dry eye disease caused by moderate meibomian gland dysfunction

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International Journal of Ophthalmology(English edition) 2020年第9期13卷 1368-1373页

作者： José-maría Sánchez-gonzález Concepción De-Hita-Cantalejo maría Carmen Sánchez-gonzález Department of Physics of Condensed Matter Optics AreaUniversity of SevilleSeville 41012Spain

AIM:To study the effect of uncrosslinked and crosslinked hyaluronic acid combined with other artificial tear components in patients with dry eye caused by moderate meibomian gland ***:Prospective,single-blind,contralateral eye *** eyes(25 patients)were *** selection for each tear type was random,and the eye drop formulations,0.4%uncrosslinked hyaluronic acid and 0.2%galactoxyloglucan(tear A)and 0.15%crosslinked hyaluronic acid,crocin,and liposomes(tear B)were *** determined dosing schedule was three times a day for six weeks,and the study participants underwent a clinical examination before and 45 d after lubricant *** Schirmer test,tear breakup time(TBUT)test,and Ocular Surface Disease Index(OSDI)questionnaire were applied before and after instillation period with both types of artificial ***:On the Schirmer test,a significant improvement was obtained with both tear A(Pmarind seed polysaccharide,and crosslinked hyaluronic acid combined with liposomes and crocin are effective for management symptoms of dry eye disease.

关键词： liposome crosslinked hyaluronic acid meibomian gland dysfunction contact lens dry eye disease

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Liver disease and erythropoietic protoporphyria:A concise review

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World Journal of Gastroenterology 2010年第36期16卷 4526-4531页

作者： maría José Casanova-gonzález maría Trapero-marugán E Anthony Jones Ricardo Moreno-Otero Department of the Gastroenterology and Hepatology Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBEREHD)Madrid 28006Spain

The porphyries are a group of metabolic disorders characterized by deficiencies in the activity of enzymes involved in the biosynthesis of *** erythropoietic protoporphyria(EPP),in the majority of cases an autosomal dominant disease,there is a mutation of the gene that encodes ferrochelatase(FECH).FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes,plasma,skin and *** prevalence of this inherited disorder oscillates between 1:75 000 and 1:200 *** manifestations of EPP appear in early infancy upon first exposure to the ***,approximately 5%-20% of patients with EPP develop liver *** of protoporphyrin in the liver is associated with cholestatic phenomena and oxidative stress that predisposes to hepatobiliary disease of varying degrees of severity,such as cholelithiasis,mild parenchymal liver disease,progressive hepatocellular disease with end-stage liver disease and acute liver *** damage is the major risk in EPP patients,so surveillance and frequent clinical and biochemical liver follow-up is *** diagnostic approach consists in detecting increased levels of protoporphyrin,decreased activity of FECH and genetic analysis of the FECH gene.A variety of nonsurgical therapeutic approaches have been adopted for the management of EPP associated with liver disease,but none of these has been shown to be unequivocally ***,some may have a place in preparing patients for liver *** transplantation does not correct the constitutional deficiency of ***,there is a risk of recurrence of liver disease after liver transplantation as a result of continuing overproduction of *** authors recommend that bone marrow transplantation should be considered in liver allograft recipients to prevent recurrence of hepatic disease.

关键词： Erythropoietic protoporphyria Protoporphyrin Liver Ferrochelatase

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A novel viewpoint in glaucoma therapeutics: enriched environment

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Neural Regeneration Research 2022年第7期17卷 1431-1439页

作者： maría F.gonzález Fleitas Damián Dorfman Ruth E.Rosenstein Laboratory of Retinal Neurochemistry and Experimental Ophthalmology Department of Human BiochemistrySchool of Medicine/CEFyBOUniversity of Buenos Aires/CONICETBuenos AiresArgentina

Glaucoma is one of the world’s most frequent visual impairment causes and leads to selective damage to retinal ganglion cells and their *** glaucoma’s most accepted risk factor is increased intraocular pressure(IOP),the mechanisms behind the disease have not been fully *** date,IOP lowering remains the gold standard;however,glaucoma patients may still lose vision regardless of effective IOP ***,the exclusive IOP control apparently is not enough to stop the disease progression,and developing new resources to protect the retina and optic nerve against glaucoma is a goal of vast clinical *** pharmacological treatments,environmental conditions have been shown to prevent neurodegeneration in the central nervous *** this review,we discuss current concepts on key pathogenic mechanisms involved in glaucoma,the effect of enriched environment on these mechanisms in different experimental models,as well as recent evidence supporting the preventive and therapeutic effect of enriched environment exposure against experimental glaucomatous ***,we postulate that stimulating vision may become a non-invasive and rehabilitative therapy that could be eventually translated to the human disease,preventing glaucoma-induced terrible sequelae resulting in permanent visual disability.

关键词： brain-derived neurotrophic factor chondroitin sulfate enriched environment glaucoma optic nerve axons optic nerve glia retinal ganglion cells visual stimulation

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Effect of climate change on drinking water supply in Santiago de Chile

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Research in Cold and Arid Regions 2013年第1期5卷 27-34页

作者： Gerardo Ahumada David Bustos maría gonzález Department of Civil Engineering Universidad de Chile Santiago Chile

Climate change is likely to increase the occurrence of floods and flashfloods that affect Santiago de Chile＇s drinking water supply system throughout the 21st century. A relationship between flashfloods in the Maipo River--Santiago＇s main raw water source, drainage area in the Maipo Alto Sub Basin and precipitation 48 hours previous to the event was found. Despite having legal guide- lines to guarantee continuity and stability in water supply, Chilean law does not specify the maximum admissible magnitude of an event. A 12% drop of average monthly flow at Maipo en E1 Manzano Station was estimated for the 2035-2065 period due to cli- mate change, meaning water suppliers would not be able to meet 90% monthly water supply security, required by Chilean law. Water suppliers would need to increase their current allotted quota of the Maipo River, from 24.5% to a percentage between 26% and 30% to comply. If the 0 ~C isotherm keeps increasing its elevation through the 21st century, more intense floods could occur because of additional drainage area granted by the elevation of the snow line, even if precipitation does not suffer a significant change. In order to withstand a five day turbidity event, 2 m3/s of groundwater, or any non river source, should be temporarily in- coroorated to the emergency dfinkin~ water production.

关键词： climate change drinking water water availability floods water supply security

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Seventeenth-century Seville houses:a survey by the Alarife Juan De Legarra(1637)

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Built Heritage 2024年第2期8卷 13-32页

作者： Pilar Moya-Olmedo maría Núñez-gonzález Fernando Vilaplana-Villajos Departamento de Ideación Gráfica Arquitectónica Escuela Técnica Superior de Arquitectura Universidad Politécnica de MadridAv.de Juan de Herrera 428040MadridSpain Departamento de Expresión Gráfica Arquitectónica Escuela Técnica Superior de Arquitectura Universidad de SevillaAv.de Reina Mercedes 2Seville41012Spain

Despite the wealth of preserved information,research on the domestic architecture of Seville has been *** of this historical data is available in survey books that were formally compiled in Seville from the Modern Age *** books had detailed descriptions and sometimes illustrations provided by surveyors who were commissioned by owners or *** intention of this study is to illustrate that the information contained in building surveys goes beyond simple descriptions or measurements often accompanied by *** are a comprehensive account that,even centuries later,help reconstruct the architecture,material culture and everyday life that no longer *** research contributes to the understanding of the domestic architectural history of Seville by focusing on one specific survey(a collection of drawings and a written description)extracted from the Hospital de las Cinco Llagas Collection,which is found in the Seville Provincial Council *** least one of the drawings and the written survey can be attributed to the Alarife(architect or master builder)Juan de Legarra,who signed them in *** research explores the architectural development of the city,offering fresh insights into its architecture,heritage,and *** supplements existing historical,visual,and written records derived from prior studies with a meticulously curated ***,it uses visualisation techniques to reconstruct buildings,augmenting the *** endeavour has yielded anticipated benefits,particularly in facilitating visual *** surveys have proven to be invaluable for historical inquiry,yielding unexpected insights through the thorough analysis of both written and graphic sources which serve as a basis for hypothetical construction plans due to their detailed ***,this study has contributed to enriching both historical and architectural *** incorporation of digital technologies into this architec

关键词： Historical documentation Survey Cultural heritage Virtual architecture Domestic architecture Archaeology

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Submicroscopic 11p13 deletion including the elongator acetyltransferase complex subunit 4 gene in a girl with language failure, intellectual disability and congenital malformations: A case report

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World Journal of Clinical Cases 2020年第21期8卷 5296-5303页

作者： Jaime Toral-Lopez Luz maría gonzález Huerta Olga Messina-Baas Sergio A Cuevas-Covarrubias Departamento de Genética Medica Centro Medico EcatepecISSEMYMEcatepec 55000México Programa de Maestría y Doctorado en Ciencias Médicas Odontológicas y de la Salud/Hospital Infantil de MéxicoUniversidad Nacional Autónoma de MéxicoMéxico 06720México Departamento de Biología Molecular Hospital General de MéxicoCuauhtémoc 06720México Departamento de Oftalmología Hospital General de MéxicoCuauhtémoc 06720México Genetica Hospital General de MéxicoCuauhtémoc 06726Mexico Sergio A Cuevas-CovarrubiasPrograma de Maestría y Doctorado en Ciencias MédicasOdontológicas y de la SaludUniversidad Nacional Autónoma de MéxicoMéxico 06720Mexico

BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic,language failure,intellectual disability and congenital malformations to strengthen our understanding of the ***,treatment is only rehabilitation and surgery for cleft lip and *** SUMmarY The proband was a 2-years-8-months-old *** history was negative for congenital malformations or intellectual *** patient had microcephaly,upward-slanting palpebral fissures,depressed nasal bridge,bulbous nose and bilateral cleft lip and *** magnetic resonance imaging showed cortical atrophy and band *** motor and intellectual development is delayed.A submicroscopic deletion in 11p13 involving the elongator acetyltransferase complex subunit 4 gene(ELP4)and a loss of heterozygosity in Xq25-q26.3 were *** There is no treatment for the ELP4 deletion caused by a submicroscopic 11p3 *** describe a second case of deletion of the ELP4 gene without aniridia,which confirms the association between ELP4 gene with several defects and absence of this ocular *** clinical data in the deletion of the ELP4 gene as cleft palate,facial dysmorphism,and changes at level brain could be associated to this gene or be part of the effect of the recessives genes involved in the loss of heterozygosity region of Xq25-26.3.

关键词： Submicroscopic 11p13 deletion Elongator acetyltransferase complex subunit 4 gene Language failure Intellectual disability Congenital malformations Case report

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Biological insights in non-small cell lung cancer

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Cancer Biology & Medicine 2023年第7期20卷 500-518页

作者： Rafael Rosell Anisha Jain Jordi Codony-Servat Eloisa Jantus-Lewintre Blake Morrison Jordi Barretina Ginesta maría gonzález-Cao Germans Trias i Pujol Research Institute Badalona 08028Spain IOR Hospital Quiron-DexeusBarcelona 08028Spain Department of Microbiology JSS Academy of Higher Education&ResearchMysuru 570015India Pangaea Oncology Hospital Quiron-DexeusBarcelona 08028Spain Department of Biotechnology Universitat Politècnica de ValenciaMixed Unit TRIAL(General University Hospital of Valencia Research Foundation and Príncipe Felipe Research Center)CIBERONCValencia 46014Spain Sumitomo Pharma Oncology Inc.CambridgeMA and LehiUT 84043USA

Lung oncogenesis relies on intracellular cysteine to overcome oxidative *** tumor types,including non-small cell lung cancer(NSCLC),upregulate the system x-c cystine/glutamate antiporter(xCT)through overexpression of the cystine transporter SLC7A11,thus sustaining intracellular cysteine levels to support glutathione *** factor erythroid 2-related factor 2(NRF2)serves as a master regulator of oxidative stress resistance by regulating SLC7A11,whereas Kelch-like ECH-associated protein(KEAP1)acts as a cytoplasmic repressor of the oxidative responsive transcription factor *** in KEAP1/NRF2 and p53 induce SLC7A11 activation in *** cystine is crucial in supplying the intracellular cysteine levels necessary to combat oxidative *** in cystine availability lead to iron-dependent lipid peroxidation,thus resulting in a type of cell death called *** inhibitors of xCT(either SLC7A11 or GPX4)induce ferroptosis of NSCLC cells and other tumor *** cystine uptake is impaired,the intracellular cysteine pool can be sustained by the transsulfuration pathway,which is catalyzed by cystathionine-B-synthase(CBS)and cystathionine g-lyase(CSE).The involvement of exogenous cysteine/cystine and the transsulfuration pathway in the cysteine pool and downstream metabolites results in compromised CD8^(+)T cell function and evasion of immunotherapy,diminishing immune response and potentially reducing the effectiveness of immunotherapeutic *** is a previously unrecognized form of regulated cell *** NSCLCs driven by EGFR,ALK,or KRAS,selective inhibitors induce pyroptotic cell death as well as *** targeted therapy,the mitochondrial intrinsic apoptotic pathway is activated,thus leading to the cleavage and activation of ***,gasdermin E is activated,thus leading to permeabilization of the cytoplasmic membrane and cell-lytic pyroptosis(indicated by characte

关键词： Solute carrier family 7 member 11(SLC7A11) nuclear factor erythroid 2-related factor 2(NRF2) ferroptosis pyroptosis KRAS G12C allele-specific inhibitors non-small cell lung cancer(NSCLC)

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