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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

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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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Evaluation of glial cell proliferation with non-invasive molecular imaging methods after stroke

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neural Regeneration Research 2021年第11期16卷 2209-2210页

作者： ana Joya Abraham martín Achucarro Basque Center for neuroscience LeioaSpain CIC biomaGUnE Basque Research and Technology Alliance(BRTA)PaseoSpain Ikerbasque Basque Foundation for Science BilbaoSpain

Glial proliferation:For the last decades,glial cells have been wrongly believed to have a mere passive supporting role for ***,this notion has clearly changed and it is now admitted that these cells are essential for the correct development and regulation of the nervous *** cell population are commonly subdivided in astrocytes,oligodendrocytes and *** the development,neural stem cells(nSCs)(called neuroepithelial progenitor cells or nPCs)transform into radial glia,the primary progenitor cells for neurons,astrocytes and oligodendrocytes(Zuchero and Barres,2015).Microglial cells,however,derive from a mesenchymal precursor infiltration,meaning that during brain development,precursors generated in the bone narrow invade the nervous parenchyma and differentiate into microglial cells(Zuchero and Barres,2015).This proliferative capacity is preserved in the adult mammalian brain,and neurogenic nSCs are stored in two restricted regions of the central nervous system(CnS),the forebrain subventricular zone(SVZ)and the hippocampal dentate gyrus(subgranular zone).These cells continue to produce neurons and glial cells during the adulthood,being activated after certain signals and leaving the quiescent state(Urbán et al.,2019).This process,in which glial progenitor cells differentiate into mature glia during development and in the adult brain to maintain and regulate brain function,is called gliogenesis(Ardaya et al.,2020).

关键词： admitted maintain supporting

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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

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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

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

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

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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

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Long-term open circuit microbial electrosynthesis system promotes methanogenesis

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Journal of Energy Chemistry 2020年第2期29卷 3-6页

作者： Raúl Mateos Adrián Escapa María Isabel San-martín Heleen De Wever ana Sotres Deepak Pant Chemical and Environmental Bioprocess Engineering Group Natural Resources Institute(IRENA)University of LeonLeon 24071Spain Department of Electrical Engineering and Automatic Systems Universidad de LeonLeon 24071Spain Reparation and Conversion Technology Flemish Institute for Technological Research(VITO)Mol 2400Belgium

Microbial electrosynthesis(MES) can potentially provide a mean for storing renewable energy surpluses as chemical energy. However, the fluctuating nature of these energy sources may represent a threat to MES, as the microbial communities that develop on the biocathode rely on the continuous existence of a polarized electrode. This work assesses how MES performance, product generation and microbial community evolution are affected by a long-period(6 weeks) power off(open circuit). Acetogenic and H2-producing bacteria activity recovered after reconnection. However, few days later syntrophic acetate oxidation bacteria and H2-consuming methanogens became dominant, producing CH4 as the main product, via electromethanogenesis and the syntrophic interaction between eubacterial and archaeal communities which consume both the acetic acid and the hydrogen present in the cathode environment. Thus,the system proved to be resilient to a long-term power interruption in terms of electroactivity. At the same time, these results demonstrated that the system could be extensively affected in both end product generation and microbial communities.

关键词： Biocathode Electromethanogenesis Microbial electrosynthesis Microbial community dynamics Methanogens Acetogens

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémartínez-Hernández Alejandro martín-belmonte Rocío Alfaro-Ruiz Miriam Fernández ana Esther Moreno-martínez Mar Cuadrado-Tejedor ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Precision medicine in pantothenate kinase-associated neurodegeneration

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neural Regeneration Research 2019年第7期14卷 1177-1185页

作者： Mónica álvarez-Córdoba Marina Villanueva-Paz Irene Villalón-García Suleva Povea-Cabello Juan M.Suárez-Rivero marta Talaverón-Rey Javier Abril-Jaramillo ana belén Vintimilla-Tosi José A.Sánchez-Alcázar Centro Andaluz de Biología del Desarrollo(CABD-CSIC-Universidad Pablo de Olavide) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos Ⅲ Centro de neurología Avanzada Centro Civet

neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal *** predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal *** the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAn) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PAnK2)which catalyzed the first reaction of the coenzyme A biosynthesis *** there is no effective treatment to prevent the inexorable course of these *** aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in ***,we have described that dermal fibroblasts obtained from PKAn patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative *** addition,PKAn fibroblasts showed a morphological senescence-like ***,pantothenate supplementation,the substrate of the PAnK2 enzyme,corrected all pathophysiological alterations in responder PKAn fibroblasts with low/residual PAnK2 enzyme ***,pantothenate treatment had no favourable effect on PKAn fibroblasts harbouring mutations associated with the expression of a truncated/incomplete *** correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAn *** observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PAnK2 in s

关键词： neurodegeneration with brain iron accumulation pantothenate kinase-associated neurodegeneration pantothenate kinase 2 pantothenate induced neurons precision medicine induced neuron fibroblast

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Quality of Life in Congenital Heart Disease Patients according to Their anatomical and Physiological Classification

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Congenital Heart Disease 2023年第2期18卷 197-206页

作者： Efrén martínez-Quintana Hiurma Estupiñán-León ana Beatriz Rojas-Brito Liuva Déniz-Déniz Alejandro Barreto-martín Fayna Rodríguez-González Cardiology Service Complejo Hospitalario Universitario Insular-Materno InfantilLas Palmas de Gran Canaria35016Spain Department of Medical and Surgical Sciences Faculty of Health SciencesUniversidad de Las Palmas de Gran CanariaLas Palmas de Gran Canaria35016Spain Ophthalmology Service Hospital Universitario de Gran Canaria Dr.NegrínLas Palmas de Gran Canaria35012Spain

Background:Living well is as important as living *** objective of this study is to assess quality of life(QoL)in congenital heart disease(CHD)according to current AHA/ACC anatomical and physiological ***:Cross-sectional study examining the World Health Organization QoL Bref questionnaire(WHOQoL-Bref)in consecutive outpatient CHD patients from a single ***:191 CHD patients were *** age was 28±13 years and 59%were male.44(23%),115(60%)and 33(17%)CHD patients showed mild,moderate and great anatomical defects respectively while 69(36%)patients were in physiological Stage A,27(14%)in Stage B,84(44%)in Stage C and 11(6%)in Stage *** significant differences were seen in relation the anatomical classification and the different sections of the WHOQoL-Bref *** patients in Stages C and D had significant lower physical domain scores than patients in the Stage A(pno significant differences were seen in the psychological,social relationships and environmental *** binary logistic regression analysis showed that having a higher educational level was a protective factor[OR 0.32(95%CI,0.12-0.87),p=0.026]while being married or cohabit was a risk factor[OR 3.46(95%CI,1.13-10.63),p=0.030]for having a worse rated ***,having a worse functional class(nYHA≥2)[OR 3.44(95%CI,1.20-9.81),p=0.021]was associated with dissatisfaction with ***:Patients with advanced physiological stages scored lower on the physiological *** statistical significance was seen,according to the anatomical and physiological classification,in the psychological,social relationship and environmental domains.

关键词： Quality of life congenital heart disease complexity

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