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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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Unveiling the brain’s symphony:exploring the necessity and sufficiency of neural networks in behavior control

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Neural Regeneration Research 2025年第1期20卷 186-187页

作者： Fernando Jose Bustos Instituto de Ciencias Biomedicas Facultad de Medicina y Facultad de Ciencias de la VidaUniversidad Andres BelloSantiagoChile Millennium Nucleus of Neuroepigenetics and plasticity(EpiNeuro) SantiagoChile

Since the pioneering work by Broca and Wernicke in the 19th century,who examined individuals with brain lesions to associate them with specific behaviors,it was evident that behaviors are complex and cannot be fully attributable to specific brain areas ***,they involve connectivity among brain areas,whether close or *** that time,this approach was considered the optimal way to dissect brain circuitry and *** pioneering efforts opened the field to explore the necessity or sufficiency of brain areas in controlling behavior and hence dissecting brain ***,the connectivity of the brain and the mechanisms through which various brain regions regulate specific behaviors,either individually or collaboratively,remain largely *** animal models,researchers have endeavored to unravel the necessity or sufficiency of specific brain areas in influencing behavior;however,no clear associations have been firmly established.

关键词： behavior connectivity neural

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Response to lipopolysaccharide in Octodon degus pups produces age-related sickness behavior but does not have effects in juveniles

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Integrative Zoology 2019年第3期14卷 235-247页

作者： Natalia RAMIREZ-OTAROLA Janyra ESpINOZA Alexis M.KALERGIS pablo SABAT department of Ecological Sciences Science FacultyUniversidad de ChileSantiagoChile Millennium Institute Immunology and Immunotherapy Departamento de Genética Molecular y MicrobiologíaFacultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile departamento de Endocrinología Facultad de MedicinaPontificia Universidad Católica de ChileSantiagoChile department of Ecology Center of Applied Ecology&SustainabilityBiological Sciences FacultyPontificia Universidad Católica de ChileSantiagoChile

During vertebrate development,the immune function is inefficient and is mainly controlled by innate *** there have been detailed studies of various aspects of innate immune function,the effects of this function in the growth of vertebrates is still not well ***,there is little information regarding how early endotoxin exposure would affect juvenile phenotypes,specifically in a non-model mammal like a precocial *** evaluated the response to an antigen and its cost in offspring of the rodent Octodon *** inoculated pups at 4 different ages(8,15,22 and 30 days after birth)with an antigen to determine the ontogeny and costs of the response to an *** assessed changes in body mass,body temperature,sickness behavior and the levels of a key mediator of the inflammatory response,the cytokine interleukin-1β.We also determined the effects of early endotoxin exposure on the resting metabolic rate of juvenile animals(i.e.90 days after birth).The cytokine levels,body mass and body temperature were unaffected by time of inoculation and ***,pups subjected to inoculation at 22 days after birth with the antigen showed reduced loco*** resting metabolic rate was not affected by early endotoxin *** results suggest that the magnitude of *** responses would not change with *** discuss whether the lack of effect of the response on body mass or body condition is caused by environmental variables or by the precocial characteristics of ***.

关键词： acute phase response ecoimmunology lipopolysaccharide precocial sickness behavior

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Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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Neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical Neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

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Nonlinear numerical assessment of the seismic response of hillside RC buildings

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Earthquake Engineering and Engineering Vibration 2021年第2期20卷 423-440页

作者： Miguel A.Gómez Edgar Giovanny Díaz-Segura Juan Carlos Vielma Civil Engineering School Pontificia Universidad Católica de ValparaísoValparaíso 2340000Chile

Major damage has been reported in hilly areas after major earthquakes,primarily because of two special conditions:the variation in the seismic ground motion due to the inclined ground surface and the irregularities caused by a stepped base level in the *** aim of this study is to evaluate possible differences in the responses of chilean hillside buildings through numerical linear-elastic and nonlinear *** the first step,a set of response-spectrum analyses were performed on four simplified 2D structures with mean base inclination angles of 0°,15°,30°,and 45°.The structures were designed to comply with chilean seismic codes and standards,and the primary response parameters were *** assess the seismic performance of the buildings,nonlinear static(pushover)and dynamic(time-history)analyses were performed with SeismoStruct *** analyses were used to compare the nonlinear response at the maximum roof displacement and the damage ***-history analyses were performed to assess the nonlinear dynamic response of the structures subjected to seismic ground motions modified by topographic *** consider the topographic modification,acceleration records were obtained from numerical models of soil,which were calculated using the rock acceleration record of the Mw 8.01985 chilean *** differences in the structure responses(roof displacements and maximum element forces and moments)were caused by the topographic effects in the seismic input motion,with the highly predominant ones being the differences caused by the step-back configuration at the base of the *** concentrations of shear forces in short walls were observed,corresponding to the walls located in the upper zone of the foundation *** response of the structures with higher angles was observed to be more prone to fragile failures due to the accumulation of shear *** though hillside buildings gain stiffness in the lower stories,resulting

关键词： topographic effect hillside buildings nonlinear analyses shear-wall buildings

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Misfolded amyloid-beta conformational variants(strains)as drivers of Alzheimer's disease neuropathology

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Neural Regeneration Research 2025年第11期20卷 3219-3220页

作者： Salvatore Saieva Rodrigo Morales department of Neurology The University of Texas Health Science Center at HoustonHoustonTXUSA Centro Integrativo de Biologia y Quimica Aplicada(CIBQA) Universidad Bernardo O’HigginsSantiagoChile

pathological and clinical variability in Alzheimer's disease(AD):AD is clinically cha racterized by progressive memory loss and cognitive *** a pathological point of view,the main features of AD are the deposition of amyloid plaques(composed of amyloid-beta,Aβ)and neurofibrillary tangles containing hyperphosphorylated Tau in the brain,accompanied by neu ronal and synaptic loss,neuroinflammation and brain atrophy(Jellinger,2022).Regardless of these common traits,growing evidence shows increased heterogen eity in the brain of AD patients considering both clinical manifestations and pathological features.

关键词： amyloid Alzheimer clinical

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Role of peripheral amyloid-β aggregates in Alzheimer’s disease: mechanistic, diagnostic, and therapeutic implications

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Neural Regeneration Research 2025年第4期20卷 1087-1089页

作者： Nazaret Gamez Rodrigo Morales department of Neurology The University of Texas Health Science Center at HoustonHoustonTXUSA Centro Integrativo de Biologia y Quimica Aplicada(CIBQA) Universidad Bernardo O’HigginsSantiagoChile

Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)***,Aβdeposits have been identified in peripheral ***,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well *** presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated *** latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of *** this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.

关键词： therapeutic amyloid latter

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Role of Salmonella enterica exposure in chilean Crohn's disease patients

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World Journal of Gastroenterology 2013年第35期19卷 5855-5862页

作者： Manuel Alvarez-Lobos Daniela p pizarro Christian E palavecino Abner Espinoza Valentina p Sebastián Juan C Alvarado patricio Ibaez Carlos Quintana Orlando Díaz Alexis M Kalergis Susan M Bueno CAREI Group (Active Cohort Registry of Inflammatory Bowel Disease) Department of Gastroenterology Facultad de MedicinaPontificia Universidad Católica de Chile departamento de Genética Molecular y Microbiología Facultad de Ciencias Biológicas Pontificia Universidad Católica de Chile School of Medicine Facultad de MedicinaPontificia Universidad Católica de Chile department of Respiratory Diseases Facultad de Medicina Pontificia Universidad Católica de Chile

AIM:To study the association between exposure toSalmonella enterica(SE)and Crohn’s disease(CD)and its clinical implications in chilean ***:Ninety-four unrelated chilean CD patients from CAREI(Active Cohort Registry of Inflammatory Bowel Disease)presenting to a single inflammatory bowel disease(IBD)unit of a University Hospital were prospectively included in this study.A complete clinical evaluation,including smoking history,was performed at the initial visit,and all the important data of clinical evolution of CD were *** samples from these CD patients and 88 healthy sex-and agematched control subjects were analyzed for exposure to SE and for their NOD2/CARD15 gene status using the presence of anti-Salmonella lipopolysaccharide antibodies[immunoglobulin-G type(IgG)]and polymerase chain reaction(pCR),*** also evaluated exposure to SE in 90 sex-and age-matched patients without CD,but with known smoking status(30 smokers,30 non-smokers,and 30 former smokers).RESULTS:CD patients comprised 54 females and 40males,aged 35.5±15.2 years at diagnosis with a mean follow-up of 9.0±6.8 *** was inflammatory in 59 patients(62.7%),stricturing in 24(25.5%)and penetrating in 15(15.5%).Thirty cases(31.9%)had lesions in the ileum,29(30.8%)had ileocolonic lesions,32(34.0%)had colonic lesions and 23(24.4%)had perianal *** CD patients(17%)were exposed to SE compared to 15(17%)of 88 healthy control subjects(p=0.8).Thirty-one CD patients(32.9%)were smokers,and 7(7.4%)were former smokers at *** the group exposed to SE,10 of 16 patients(62.5%)were active smokers compared to 21 of 78 patients(26.9%)in the unexposed group(p=0.01).On the other hand,10 of 31 smoking patients(32%)were exposed to SE compared to 5 of 56 nonsmoking patients(9%),and one of the seven former smokers(14%)(p=0.01).In the group of 90 patients without CD,but whose smoking status was known,there was no differ-ence in exposure to SE[3 of 30 smokers(10%),5 of30 non-s

关键词： Crohn’s disease Salmonella Infection Tobacco Smoking Environmental factors

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COVID-19 and Indirect Liver Injury:A Narrative Synthesis of the Evidence

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Journal of Clinical and Translational Hepatology 2021年第5期9卷 760-768页

作者： Francisco Idalsoaga Gustavo Ayares Juan pablo Arab Luis Antonio Díaz departamento de Gastroenterología Escuela de MedicinaPontificia Universidad Católica de ChileSantiagoChile Centro de Envejecimiento y Regeneración(CARE) Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)*** most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase,with a prevalence of 16-53%among *** with severe coronavirus disease 2019(COVID-19)seem to have higher rates of acute liver dysfunction,and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during *** with chronic liver diseases also have a higher risk of severe disease and mortality(mainly seen in patients with metabolic-associated fatty liver disease).Several pathways of damage have been proposed in the liver involvement of COVID-19 patients;although,the end-cause is most likely *** liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 *** enzyme is expressed widely in cholangiocytes and less in *** factors attributed to liver damage include drug-induced liver injury,uncontrolled release of proinflammatory molecules(“cytokine storm”),pneumonia-associated hypoxia,and direct damage by the *** steatosis,vascular thrombosis,fibrosis,and inflammatory features(including Kupffer cell hyperplasia)are the most common liver histopathological findings in deceased COVID-19 patients,suggesting important indirect mechanisms of liver *** this translational medicinebased narrative review,we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19,the histopathological findings,and the impact of these mechanisms in patients with chronic liver disease.

关键词： COVID-19 SARS-CoV-2 Liver hepatitis Liver injury Novel coronavirus

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Numerical modeling of cracking pattern's influence on the dynamic response of thickened tailings disposals: a periodic approach

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Earthquake Engineering and Engineering Vibration 2018年第1期17卷 179-190页

作者： Gabriel Ferrer Esteban Sáez Christian Ledezma School of Engineering Pontificia Universidad Católica de Chile National Research Center for Integrated Natural Disaster Management

Copper production is an essential component of the chilean economy. During the extraction process of copper, large quantities of waste materials（tailings） are produced, which are typically stored in large tailing ponds. Thickened Tailings Disposal（TTD） is an alternative to conventional tailings ponds. In TTD, a considerable amount of water is extracted from the tailings before their deposition. Once a thickened tailings layer is deposited, it loses water and it shrinks, forming a relatively regular structure of tailings blocks with vertical cracks in between, which are then filled up with ＂fresh＂ tailings once the new upper layer is deposited. The dynamic response of a representative column of this complex structure made out of tailings blocks with softer material in between was analyzed using a periodic half-space finite element model. The tailings＇ behavior was modeled using an elasto-plastic multi-yielding constitutive model, and chilean earthquake records were used for the seismic analyses. Special attention was given to the liquefaction potential evaluation of TTD.

关键词： Thickened tailings Liquefaction periodic modeling

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