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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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Oleanolic acid:a promising neuroprotective agent for cerebral ischemia

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Neural Regeneration Research 2015年第4期10卷 540-541页

作者： Caltana Laura Nieto María Luisa Brusco Alicia instituto de biología Celulary Neurociencia IBCN(UBA-CONICET)Buenos AiresArgentina instituto biologíay genética molecular CSIC-UVAValladolidSpain

Stroke is considered the most common and severely disabling neurological disease. It is one of the leading causes of death after heart disease and cancer, causing 10% deaths worldwide and involving risk factors such as smoking, obesity and nutritional disbalance. Disability affects 75% of stroke survivors through severe mental and/or physical impairment depending on the affected brain area （Go et al., 2014）.

关键词： acid Oleanolic acid

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Non-steroidal anti-inflammatory drugs(NSAIDs) and neuroprotection in the elderly a view from the mitochondria

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Neural Regeneration Research 2015年第9期10卷 1371-1372页

作者： María Calvo-Rodríguez Lucía Nú?ez Carlos Villalobos instituto de biologíay genética molecular (IBGM) Consejo Superior de Investigaciones Científicas (CSIC) and Universidad de Valladolid

The most important risk factor for stroke and neurodegeneration is aging. In fact, survival after stroke diminishes largely with aging. In fact, recovery after brain artery occlusion is dramatically worsened by aging, even normal aging is associated with neuron damage and cognitive decline. Mechanisms involved in aging-related, cognitive decline and susceptibility to neuron damage in stroke and neurode- generation are largely unknown. One of the most important mech- anisms contributing to neural dysfunction and death is excitotox- icity. This process is based on the fact that the excessive glutamate receptor stimulation may lead to neuronal damage. This overstim- ulation may be due to increased concentration of glutamate, or the prolonged activation of receptors.

关键词： NSAIDs Non-steroidal anti-inflammatory drugs and neuroprotection in the elderly a view from the mitochondria view

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Calcitriol induces post-thawed bovine sperm capacitation

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BIOCELL 2023年第5期47卷 1135-1143页

作者： ANA CECILIA LIAUDAT FRANCISCA EBEL BIANCA ANA OPIZZO MARINA AURORA GONZALEZ DAMIÁN BLOIS PABLO BOSCH NANCY RODRIGUEZ Departamento de biología molecular Instituto de Biotecnología Ambiental y Salud(INBIAS)Río Cuarto5800Argentina

Background:Capacitation is a set of physiological changes sperms undergo to acquire fertilizing *** vivo,this process is directly associated with high calcium levels in sperm ***,the vitamin D hypercalcemic metabolite,is related to human sperm motility,capacitation,and acrosome *** work aimed to study the effect of calcitriol on bull sperm quality parameters and ***:One million freezethawed spermatozoa were obtained from different bulls and treated with 20 nM of calcitriol for 30 *** cells(negative control)and treated ones with calcitriol or heparin(100μg/mL,positive capacitation control)were evaluated for motility,viability,and functional ***(70μM,30 min)treatment was included as a reactive oxygen species(ROS)positive sperm ***:The results elucidated that sperm exposed to 20 nM calcitriol showed higher viability,vigor,and capacitation than their positive and negative *** percentage of sperm with intact plasma and acrosome membranes,mitochondrial membrane potential(ΔΨm),and phosphatidylserine externalization was similar in all the conditions evaluated,while ROS production was higher with heparin and menadione-treated groups than the calcitriol group or negative ***:Our results indicate that calcitriol induces the capacitation of thawed bull spermatozoa and maintains acceptable values of progressive motility,viability,and vigor without altering key biological parameters such as redox status,ΔΨm,and cell death.

关键词： Bovine Sperm capacitation Calcitriol Cell viability Plasma membrane integrity Reactive oxygen species

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C3G contributes to platelet activation and aggregation by regulating major signaling pathways

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2103-2117页

作者： Sara Gutiérrez-Herrero Cristina Fernández-Infante Luis Hernández-Cano Sara Ortiz-Rivero Carlos Guijas Víctor Martín-Granado JoséRamón González-Porras Jesús Balsinde Almudena Porras Carmen Guerrero instituto de biología molecular y Celular del Cáncer(IMBCC) University of Salamanca-CSICSalamancaSpain instituto de Investigación Biomédica de Salamanca(IBSAL) SalamancaSpain instituto de biología y genética molecular(IBGM) Consejo Superior de Investigaciones Científicas(CSIC)University of ValladolidValladolidSpain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM) MadridSpain Departamento de Hematologiá Hospital Universitario de Salamanca(HUS)SalamancaSpain Departamento de Bioquímica y biología molecular Facultad de FarmaciaComplutense University of Madrid.Instituto de Investigación Sanitaria del Hospital Clínico San Carlos(IdISSC)MadridSpain Departamento de Medicina University of SalamancaSalamancaSpain

C3G is a GEF(guanine nucleotide exchange factor)for Rap GTPases,among which the isoform Rap1b is an essential protein in platelet *** transgenic mouse models with platelet-specific overexpression of C3G or mutant C3GΔCat,we have unveiled a new function of C3G in regulating the hemostatic function of platelets through its participation in the thrombin-PKCRap1b pathway.C3G also plays important roles in angiogenesis,tumor growth,and metastasis through its regulation of the platelet *** addition,C3G contributes to megakaryopoiesis and ***,we used a platelet-specific C3G-KO mouse model to further support the role of C3G in hemostasis.C3G-KO platelets showed a significant delay in platelet activation and aggregation as a consequence of the defective activation of Rap1,which resulted in decreased thrombus formation in ***,we explored the contribution of C3G-Rap1b to platelet signaling pathways triggered by thrombin,PMA or ADP,in the referenced transgenic mouse model,through the use of a battery of specific *** found that platelet C3G is phosphorylated at Tyr504 by a mechanism involving *** phosphorylation was shown to be positively regulated by ERKs through their inhibition of the tyrosine phosphatase ***,C3G participates in the ADP-P2Y12-PI3K-Rap1b pathway and is a mediator of thrombin-TXA2 ***,it inhibits the synthesis of TXA2 through cPLA2 *** together,our data reveal the critical role of C3G in the main pathways leading to platelet activation and aggregation through the regulation of Rap1b.

关键词： C3G platelet activation

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Comparative mitogenome phylogeography of two anteater genera (Tamandua and Myrmecophaga;Myrmecophagidae, Xenarthra): Evidence of discrepant evolutionary traits

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Zoological Research 2021年第5期42卷 525-547页

作者： Manuel Ruiz-García Daniel Pinilla-Beltrán Oscar E.Murillo-García Christian Miguel Pinto Jorge Brito Joseph Mark Shostell Laboratorio de genética de Poblaciones molecular-biología Evolutiva Departamento de BiologíaFacultad de CienciasPontificia Universidad JaverianaBogotáDC 110231Colombia Grupo de Investigación en Ecología Animal Departamento de BiologíaFacultad de Ciencias Naturales y ExactasUniversidad del ValleApartado AéreoCali 25360Colombia instituto de Ciencias Biológicas Escuela Politécnica NacionalQuito 17012759Ecuador instituto Nacional de Biodiversidad(INABIO) Quito 170135Ecuador Math Science and Technology DepartmentUniversity of Minnesota CrookstonCrookstonMN 56716USA

The species within Xenarthra(sloths,anteaters,and armadillos)are quintessential South American *** the three groups,Vermilingua(anteaters)contains the fewest extant and paleontological ***,we sampled and sequenced the entire mitochondrial genomes(mitogenomes)of two Tamandua species(Tamandua tetradactyla and ***)(n=74)from Central and South America,as well as Myrmecophaga tridactyla(n=41)from South *** Tamandua,we detected three different *** oldest(THI)contained many specimens with the *** morphotype(but also several with the *** morphotype)and originated in southeastern South America(currently Uruguay)before moving towards northern South America,where the THII haplogroup *** primarily contained specimens with the *** morphotype(but also several with the *** morphotype)and was distributed in Central America,Colombia,and *** and THII yielded a genetic distance of 4%.THII originated in either northern South America or“in situ”in Central America with haplogroup THIII,which consisted of~50%*** and 50%*** *** was mostly located in the same areas as THII,i.e.,Central America,Ecuador,and Colombia,though mainly in the *** three haplogroups overlapped in Colombia and ***,*** and *** were not reciprocally *** this reason,we considered that a unique species of Tamandua likely exists,i.e.,*** contrast to Tamandua,*** did not show different morphotypes throughout its geographical range in the ***,two very divergent genetic haplogroups(MHI and MHII),with a genetic distance of~10%,were *** basal haplogroup,MHI,originated in northwestern South America,whereas the more geographically derived haplogroup,MHII,overlapped with MHI,but also expanded into central and southern South ***,Tamandua migrated from south to north whereas Myrmecophaga migrated from

关键词： Anteaters genetic diversity Mitogenomes Myrmecophaga Neotropics Phylogeography Spatial structure Tamandua

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molecular complexity of visual mapping: a challenge for regenerating therapy

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Neural Regeneration Research 2020年第3期15卷 382-389页

作者： Mara Medori Gonzalo Spelzini Gabriel Scicolone CONICET–Universidad de Buenos Aires Instituto de Biología Celular y Neurociencias“Prof.E.De Robertis”(IBCN)Ciudad Autónoma de Buenos AiresArgentina Universidad de Buenos Aires Facultad de MedicinaDepartamento de Biología CelularHistologíaEmbriología y GenéticaCiudad Autónoma de Buenos AiresArgentina

Investigating the cellular and molecular mechanisms involved in the development of topographically ordered connections in the central nervous system constitutes an important issue in neurobiology because these connections are the base of the central nervous system normal *** dominant model to study the development of topographic maps is the projection from the retinal ganglion cells to the optic tectum/*** expression pattern of Eph/ephrin system in opposing gradients both in the retina and the tectum,labels the local addresses on the target and gives specific sensitivities to growth cones according to their topographic origin in the *** rigid precision of normal retinotopic mapping has prompted the chemoaffinity hypothesis,positing axonal targeting to be based on fixed biochemical affinities between fibers and ***,several lines of evidence have shown that the mapping can adjust to experimentally modified targets with flexibility,demonstrating the robustness of the guidance *** we discuss the complex ways the Ephs and ephrins interact allowing to understand how the retinotectal mapping is a precise but also a flexible process.

关键词： axon growth axon guidance development Eph and ephrin mapping regeneration retinal ganglion cells retino-tectal system

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Implications of receptor for advanced glycation end products for progression from obesity to diabetes and from diabetes to cancer

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World Journal of Diabetes 2023年第7期14卷 977-994页

作者： Andrea Garza-Campos José Roberto Prieto-Correa José Alfredo Domínguez-Rosales Zamira Helena Hernández-Nazará Programa de Doctorado en Ciencias en biología molecular en Medicina Universidad de GuadalajaraGuadalajara 44340JaliscoMexico Departamento de biología molecular y genómica Instituto de Investigación en Enfermedades Crónico-DegenerativasUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico

Obesity and type 2 diabetes mellitus(T2DM)are chronic pathologies with a high incidence *** share some pathological mechanisms,including hyperinsulinemia,the production and release of hormones,and *** above,over time,affects other systems of the human body by causing tissue hypoxia,low-grade inflammation,and oxidative stress,which lay the pathophysiological groundwork for *** leading causes of death globally are T2DM and *** main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death(i.e.,damage-associated molecular patterns)such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products(RAGE)-a multiligand receptor involved in inflammatory and metabolic and neoplastic *** review analyzes the latest advanced reports on the role of RAGE in the development of obesity,T2DM,and cancer,with an aim to understand the intracellular signaling mechanisms linked with cancer *** review also explores inflammation,oxidative stress,hypoxia,cellular senescence,RAGE ligands,tumor microenvironment changes,and the“cancer hallmarks”of the leading tumors associated with *** assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.

关键词： Type 2 diabetes Cancer Obesity Advanced glycation end product receptor Receptor for advanced glycation end products Glycation end products,advanced

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MicroRNAs dysregulation in hepatocellular carcinoma: Insights in genomic medicine

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World Journal of Hepatology 2015年第11期7卷 1530-1540页

作者： Iván Lyra-González Laura E Flores-Fong Ignacio González-García David Medina-Preciado Juan Armendáriz-Borunda Departamento de biología molecular y genómica CUCS Universidad de Guadalajara Instituto de Biología Molecular en Medicina y Terapia Génica O.P.D. Hospital Civil de Guadalajara "Fray Antonio Alcalde" O.P.D. Hospital Civil de Guadalajara "Juan I. Menchaca" Departamento de biología molecular y genómica CUCS Universidad de Guadalajara

Hepatocellular carcinoma(HCC) is the leading primary liver cancer and its clinical outcome is still poor. MicroRNAs(mi RNAs) have demonstrated an interesting potential to regulate gene expression at post-transcriptional level. Current findings suggest that mi RNAs deregulation in cancer is caused by genetic and/or epigenetic, transcriptional and post-transcriptional modifications resulting in abnormal expression and hallmarks of malignant transformation: aberrant cell growth, cell death, differentiation, angiogenesis, invasion and metástasis. The important role of mi RNAs in the development and progression of HCC has increased the efforts to understand and develop mechanisms of control overt this single-stranded RNAs. Several studies have analyzed tumoral response to the regulation and control of deregulated mi RNAs with good results in vitro and in vivo, proving that targeting aberrant expression of mi RNAs is a powerful anticancer therapeutic. Identification of up and/or down regulated mi RNAs related to HCC has led to the discovery of new potential application for detection of their presence in the affected organism. Mi RNAs represent a relevant new target for diagnosis, prognosis and treatment in a wide variety of pathologic entities, including HCC. This manuscript intends to summarize current knowledge regarding mi RNAs and their role in HCC development.

关键词： Hepatocellular carcinoma MicroRNAs Regulation Therapeutic targets

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Gut microbiota in a population highly affected by obesity and type 2 diabetes and susceptibility to COVID-19

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World Journal of Gastroenterology 2021年第41期27卷 7065-7079页

作者： Jaime García-Mena Karina Corona-Cervantes Daniel Cuervo-Zanatta Tizziani Benitez-Guerrero JuanManuel Vélez-Ixta Norma Gabriela Zavala-Torres Loan Edel Villalobos-Flores Fernando Hernández-Quiroz Claudia Perez-Cruz Selvasankar Murugesan Fernando Guadalupe Bastida-González Paola Berenice Zárate-Segura Departamento de genética y biología molecular Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico City 07360CDMXMexico Departamento de genética y biología molecular and Departamento de Farmacología Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico City 07360CDMXMexico Departamento de Farmacología Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico City 07360CDMXMexico Department of Mother and Child Health SIDRA MedicineDoha 26999Qatar Laboratorio Estatal de Salud Pública del Estado de México ISEMToluca de Lerdo 50180Estado de MéxicoMexico Escuela Superior de Medicina Instituto Politécnico NacionalMexico City 11340CDMXMexico

Coronavirus disease 2019(COVID-19)is a disease produced by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and it is currently causing a catastrophic pandemic affecting humans *** disease has been lethal for approximately 3.12 million people around the world since January ***,among the most affected countries,Mexico ranks third in deaths after the United States of America and *** the high number of deceased people might also be explained by social aspects and lifestyle customs in Mexico,there is a relationship between this high proportion of deaths and comorbidities such as high blood pressure(HBP),type 2 diabetes,obesity,and metabolic *** official epidemiological figures reported by the Mexican government have indicated that 18.4%of the population suffers from HBP,close to 10.3%of adults suffer from type 2 diabetes,and approximately 36.1%of the population suffers from *** in the gut microbiota(GM)have been associated with these diseases and with COVID-19 severity,presumably due to inflammatory *** data about the association between GM dysbiosis and metabolic diseases could suggest that the high levels of susceptibility to SARSCoV-2 infection and COVID-19 morbidity in the Mexican population are primarily due to the prevalence of type 2 diabetes,obesity,and metabolic syndrome.

关键词： SARS-CoV-2 COVID-19 High blood pressure Hypertension Type 2 diabetes Obesity Metabolic syndrome Gut microbiota Immunity

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