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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)

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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neural Regeneration Research 2025年第2期20卷 343-353页

作者： ana Milena Silva Olaya Fernanda Martins Almeida ana Maria Blanco Martinez Suelen Adriani Marques PhD Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and nCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

Sex differences in Alzheimer's disease:an urgent research venue to follow

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neural Regeneration Research 2024年第12期19卷 2569-2570页

作者： Raquel jiménez-Herrera ana Contreras Juan D.navarro-López Lydia jiménez-Díaz neurophysiology&Behavior Lab University of Castilla-La ManchaSchool of Medicine of Ciudad RealCiudad RealSpain

Due to increasing life expectancy,the amount of people with dementia worldwide is expected to experience a substantial rise,with estimates indicating a growth from 55 million in 2019 to a staggering 139 million by the... 详细信息

关键词： Alzheimer predominant estimates

VAMP2 is implicated in the secretion of antibodies by human plasma cells and can be replaced by other synaptobrevins

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Cellular & Molecular Immunology 2018年第4期15卷 353-366页

作者： Laura Gómez-Jaramillo Raquel Romero-García Gema jiménez-Gómez Lisa Riegle ana belén Ramos-Amaya JoséAntonio Brieva Marie Kelly-Worden Antonio Campos-Caro Unidad de Investigación Hospital Universitario Puerta del MarCádizSpain Department of Biology Ball State UniversityMuncieINUSA

The production and secretion of antibodies by human plasma cells(PCs)are two essential processes of humoral *** secretion process relies on a group of proteins known as soluble n-ethylmaleimide-sensitive factor attachment protein receptors(SnAREs),which are located in the plasma membrane(t-SnAREs)and in the antibody-carrying vesicle membrane(v-SnARE),and mediate the fusion of both *** have previously shown that SnAP23 and STX4 are the t-SnAREs responsible for antibody ***,using human PCs and antibody-secreting cell lines,we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein(VAMP)isoforms,demonstrating that all isoforms(with the exception of VAMP1)are expressed by the referenced ***,the functional role in antibody secretion of each expressed VAMP isoform was tested using *** results show that VAMP2 may be the v-SnARE involved in vesicular antibody *** further support this conclusion,we used tetanus toxin light chain to cleave VAMP2,conducted experiments to verify co-localization of VAMP2 in antibody-carrying vesicles,and demonstrated the coimmunoprecipitation of VAMP2 with STX4 and SnAP23 and the in situ interaction of VAMP2 with *** together,these findings implicate VAMP2 as the main VAMP isoform functionally involved in antibody secretion.

关键词： exocytosis human immunoglobulin plasma cells VAMP proteins

The Janus face of n-terminal lysines in α-synuclein

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neural Regeneration Research 2020年第10期15卷 1840-1841页

作者： ana belén Uceda Laura Mari?o Miquel Adrover Institut Universitari d’Investigació en Ciències de la Salut (IUnICS) Institut d’Investigació Sanitària Illes Balears (Id ISBa) Departament de Química Universitat de les Illes Balears

Parkinson’s disease(PD)is the second most prevalent progressive neurodegenerative disorder after Alzheimer’s *** usually starts with a tremor in the extremities(usually in the hands)and gradually evolves with other symptoms such as bradykinesia,muscle stiffness,impaired posture,loss of automatic movements or speech *** symptoms worsen as the condition progresses and eventually lead to death.

关键词： impaired Alzheimer eventually

Open versus laparoscopic cholecystectomies in patients with or without type 2 diabetes mellitus in Spain from 2003 to 2013

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Hepatobiliary & Pancreatic Diseases International 2016年第5期15卷 525-532页

作者： JoséM de Miguel-Yanes Manuel Méndez-Bailón Rodrigo jiménez-García Valentín Hernández-Barrera napoleón Pérez-Farinós Fernando Turégano nuria munoz-Rivas ana López-de-Andrés Internal Medicine Department Hospital General Universitario“Gregorio Maranón”46Doctor Esquerdo28007MadridSpain Internal Medicine Department Hospital Clínico San CarlosCalle Profesor Martín Lagos28040MadridSpain Preventive Medicine and Public Health Department Health Sciences FacultyRey Juan Carlos UniversityAvenida de AtenasAlcorcón28292MadridSpain Spanish Agency of Alimentary Safety and nutrition Ministry of HealthSocial Policy and Equality56Alcalá28071MadridSpain Internal Medicine Department Hospital Infanta Leonor80Avenida Gran Vía del Este28031MadridSpain Surgery Department Hospital General Universitario“Gregorio Maranón”46Doctor Esquerdo28007MadridSpain

BACKGROUnD: This study aimed to compare the rates of open and laparoscopic cholecystectomies and outcomes in patients with or without type 2 diabetes mellitus (T2DM) in Spain from 2003 to 2013. METHODS: We collected all cases of open and laparoscopic cholecystectomies using national hospital discharge data and evaluated the annual cholecystectomy rates stratiifed by T2DM status. We analyzed tendency for in-hospital mortality (IHM). We also analyzed the impact of T2DM on IHM in patients who underwent cholecystectomies. RESULTS: We identiifed 611 533 cholecystectomies (71.3%laparoscopic) in the patients, in whom 78 227 (12.8%) patients had T2DM. The rates of open cholecystectomies were 3-fold higher (130.0/105 vs 41.1/105) in patients with T2DM than in those without T2DM, and the rate of laparoscopic cholecys-tectomies was almost 2-fold higher (195.2/105 vs 111.8/105) in patients with T2DM. The annual rate of laparoscopic pro-cedures showed an 11-year relative increase of 88.3% (from 117.0/105 to 220.3/105) in T2DM and 49.2% (from 79.2/105 to 118.2/105) in patients without T2DM (Pn procedures showed an 11-year relative decrease of 27.6% in patients with T2DM and 37.9% in those without T2DM (Pncy laparoscopic cho-lecystectomy was increased in the 11 years, whereas the rate of emergency open cholecystectomies was decreased (both Panalysis revealed that older age, higher comorbidity and emergency cholecystectomy were associated with a higher IHM. Compared with patients without T2DM, patients with T2DM demonstrated a lower IHM after open cholecystectomy [OR=0.82 (0.78-0.87)], but a higher IHM after laparoscopic cholecystectomy (OR=1.18 (1.03-1.35))Time-trend analyses showed a signiifcant reduction in IHM in patients with or without T2DM after the two procedures. COnCLUSIOn: The rate of cholecystectomy was higher in patients with T2DM, and laparoscopic cholecystectomy was p

关键词： diabetes mellitus cholecystectomy mortality in-hospital mortality

Hepatitis C virus nS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment

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World Journal of Gastroenterology 2017年第25期23卷 4538-4547页

作者： Paloma munoz de Rueda José Manuel Fuentes RodríguezRosa Quiles Pérez ana Gila Medina ana belén Martínálvarez Jorge Casado Ruíz ángeles Ruíz Extremera Javier Salmerón Research Support Unit San Cecilio University Hospital of Granada Instituto de Investigación Biosanitaria CIBERehd Instituto de Salud Carlos III Unit for Clinical Management of Digestive Diseases San Cecilio University Hospital of Granada Granada University

To determine the number of mutations in the nS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODSSequences within HCV nS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFn-α), n = 49; IFn-α + ribavirin (RBV), n = 75; pegylated (peg) IFn-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (nVR). RESULTSFor both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in nVR (SVR vs nVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). COnCLUSIOnThe obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.

关键词： Interferon-based therapy Interferon-free therapy Chronic hepatitis C nS5A region Sustained virological response number of mutations

The Development of Sino-Ecuadorian Economic Relations——Based on the Perspective of Comparative analysis about Ecuadorian-Sino and Peru-Sino Economic Relations

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The Development of Sino-Ecuadorian Economic Relations——Bas...

作者： EGAS GALLEGOS ana belén 华东师范大学

学位级别：硕士

随着中国国际地位的提升,中国通过贸易和资本外流对拉丁美洲产生了重要影响。这些资本外流已经发展成基础设施、融资和外国直接投资项目。在拉丁美洲地区,厄瓜多尔是为了寻找替代发展的途径,而与中国建立起密切经济联系的国家之一。本... 详细信息

随着中国国际地位的提升,中国通过贸易和资本外流对拉丁美洲产生了重要影响。这些资本外流已经发展成基础设施、融资和外国直接投资项目。在拉丁美洲地区,厄瓜多尔是为了寻找替代发展的途径,而与中国建立起密切经济联系的国家之一。本文重点关注2007-2017年期间中厄发展情况,以深入探讨“与中国的双边关系对厄瓜多尔的发展有何贡献”这一问题。这项研究对于厄瓜多尔等拉美国家具有重要意义,使其明确能否依靠与中国的经济关系获得持续的发展。本文提供了中国对外贸易和对外直接投资的数据,对理论分析进行了概述,并对各国制定的政策、法律和战略进行了解释。为了验证和支撑研究中提出的论点,我将中国与秘鲁的经济关系作为对照,来改进厄瓜多尔的经济战略。之所以选择秘鲁,是因为他在现实中与厄瓜多尔有着很多相似的地方,而且与中国有着更高水平的经济合作。我的初步研究发现,厄瓜多尔必须提高其在地区合作中的参与度,促进互补性经济,实现工业经济的共同增长,以免成为仅仅依靠资源的国家。如果不能实现这一目标,像厄瓜多尔这样的小国将永远不能维护其有长期利益,与中国的经济联系也仅是一种依附关系。本研究也希望对理解在拉美的COFDI做出贡献。

关键词：中国厄瓜多尔外国直接投资国际贸易秘鲁双边关系

Beta-blocker therapy in elderly patients with renal dysfunction and heart failure

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Journal of Geriatric Cardiology 2021年第1期18卷 20-29页

作者： Juan Martínez-Milla Marcelino Cortés García Julia Anna Palfy Mikel Taibo Urquía Marta López Castillo ana Devesa Arbiol ana Lucía Rivero Monteagudo María Luisa Martín Mariscal Inés jiménez-Varas Sem Briongos Figuero Juan Antonio Franco-Pelaéz JoséTuñón Department of Cardiology Hospital Universitario Fundación Jiménez Díaz-Quirónsalud Centro nacional de Investigaciones Cardiovasculares MadridSpain Department of Cardiology Hospital Central de Asturias Department of Cardiology Hospital Universitario Ruber-Quirónsalud Department of Cardiology Hospital Universitario Infanta Leonor Department of Endocrinology Hospital Clínico San Carlos Universidad Autónoma de Madrid CIBERCV MadridSpain

OBJECTIVE To assess the role of beta-blockers(BB)in patients with chronic kidney disease(CKD)aged≥75 *** AnD RESULTS From January 2008 to July 2014,we included 390 consecutive patients≥75 years of age with ejection fraction≤35%and glomerular filtration rate(GFR)≤60 m L/min per 1.73 m^*** analyzed the relationship between treatment with BB and mortality or cardiovascular *** mean age of our population was 82.6±4.1 *** ejection fraction was 27.9%±6.5%.GFR was 60-45 m L/min per 1.73 m^2 in 50.3%of patients,45-30 m L/min per 1.73 m^2 in 37.4%,andn per 1.73 m^2 in 12.3%.At the conclusion of follow-up,67.4%of patients were receiving *** median follow-up was28.04(IR:19.41-36.67)*** the study period,211 patients(54.1%)died and 257(65.9%)had a major cardiovascular event(death or hospitalization for heart failure).BB use was significantly associated with a reduced risk of death(HR=0.51,95%CI:0.35-0.74;Pnts receiving BB consistently showed a reduced risk of death across the different stages of CKD:stage IIIa(GFR=30-45 m L/min per 1.73 m^2;HR=0.47,95%CI:0.26-0.86,Pn per 1.73 m^2;HR=0.55,95%CI:0.26-1.06,P=0.007),and stages IV and V(GFRn per 1.73 m~2;HR=0.29,95%CI:0.11-0.76;P=0.047).COnCLUSIOnS The use of BB in elderly patients with HFr EF and renal impairment was associated with a better *** of BB should be encouraged when possible.

关键词： CKD GFR Beta-blocker therapy in elderly patients with renal dysfunction and heart failure