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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

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)

NEW HYBRID CONJUGATE GRADIENT METHOD As A CONVEX COMBINATION OF Ls AND FR METHODs

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Acta Mathematica scientia 2019年第1期39卷 214-228页

作者： sne?ana s.DJORDJEVI? Faculty of Technology University of Nis

In this paper, we present a new hybrid conjugate gradient algorithm for unconstrained optimization. This method is a convex combination of Liu-storey conjugate gradient method and Fletcher-Reeves conjugate gradient method. We also prove that the search direction of any hybrid conjugate gradient method, which is a convex combination of two conjugate gradient methods, satisfies the famous D-L conjugacy condition and in the same time accords with the Newton direction with the suitable condition. Furthermore, this property doesn't depend on any line search. Next, we also prove that, moduling the value of the parameter t,the Newton direction condition is equivalent to Dai-Liao conjugacy *** strong Wolfe line search conditions are *** global convergence of this new method is *** comparisons show that the present hybrid conjugate gradient algorithm is the efficient one.

关键词： hybrid conjugate gradient method convex combination Dai-Liao conjugacy condition Newton direction

Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged froms transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

Abscisic acid, a promising therapeutic molecule to prevent Alzheimer’s and neurodegenerative diseases

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Neural Regeneration Research 2020年第6期15卷 1035-1036页

作者： ana María sánchez-Pérez Department of Medicine Universitat Jaume I

Neuroinflammatory processes induce neuronal damage and underlie the onset of neurodegenerative pathologies,including Alzheimer’s disease(AD)(Calsolaro and Edison,2016).several conditions,ranging from emotional stress to metabolic syndrome,including traumatic brain injury,chronic infections or gut microbiota disruption can cause or aggravate ***,aging is the major factor associated with neurodegenerative diseases.

关键词： degenerative Alzheimer diseases

spatial distribution of archaeal and bacterial ammonia oxidizers in the littoral buffer zone of a nitrogen-rich lake

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Journal of Environmental sciences 2012年第5期24卷 790-799页

作者： Huub J. M. Op den camp Department of Microbiology IWWR Radboud University Nijmegen

The spatial distribution and diversity of archaeal and bacterial ammonia oxidizers （AOA and AOB） were evaluated targeting amoA genes in the gradient of a littoral buffer zone which has been identified as a hot spot for N cycling. Here we found high spatial heterogeneity in the nitrification rate and abundance of ammonia oxidizers in the five sampling sites. The bacterial amoA gene was numerically dominant in most of the surface soil but decreased dramatically in deep layers. Higher nitrification potentials were detected in two sites near the land/water interface at 4.4–6.1 μg NO2-N/（g dry weight soil·hr）, while only 1.0–1.7 μg NO2-N/（g dry weight soil·hr） was measured at other sites. The potential nitrification rates were proportional to the amoA gene abundance for AOB, but with no significant correlation with AOA. The NH4＋ concentration was the most determinative parameter for the abundance of AOB and potential nitrification rates in this study. Higher richness in the surface layer was found in the analysis of biodiversity. Phylogenetic analysis revealed that most of the bacterial amoA sequences in surface soil were affiliated with the genus of Nitrosopira while the archaeal sequences were almost equally affiliated with Candidatus ‘Nitrososphaera gargensis’ and Candidatus ‘Nitrosocaldus yellowstonii’. The spatial distribution of AOA and AOB indicated that bacteria may play a more important role in nitrification in the littoral buffer zone of a N-rich lake.

关键词： littoral zone ammonia oxidation archaea bacteria heterogeneity abundance

Endophyte infection of Festuca eskia enhances seedling survival to drought and cutting at the expense of clonal expansion

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Journal of Plant Ecology 2011年第4期4卷 201-208页

作者： anaïs Gibert Laurent Hazard Institut National de la Recherche Agronomique UMR 1248 AGIR31320 Castanet TolosanFrance

symbiotic relationships between fungal endophytes and grass species are known to increase stress resistance in the grass host;however,there is little evidence to suggest that the positive effects occur early in the grass life *** this study,we explored the effects of the endophyte Epichloe¨festucae on the growth and survival of Festuca eskia seedlings under drought and frequent cutting *** Festuca eskia seedlings were collected from the western part of the plant repartition area in a non-symbiotic population located in a mesic and heavily grazed site(W-Ns)and from the eastern part in a symbiotic population from a xeric and lightly grazed site(E-s).The E-s population was experimentally freed from its endophyte(E-F).Two greenhouse experiments were conducted to compare growth and survival between the three seedling types under drought stress and frequent *** the first experiment,126 seedlings per seedling type(n=378)were grown for 6 weeks under non-limiting conditions before the cessation of *** 3 weeks without irrigation,full irrigation was restored for 10 days to measure the survival *** length,leaf elongation rate and survival rate were assessed per *** the second experiment,156 seedlings per seedling type(n=468)were grown under non-limiting *** seedlings were cut to 3 cmhigh,twice a week,during the first month of *** elongation and tillering were monitored on 52 seedlings per seedling *** each type,seedling survival rate was determined by the number of plants alive after 10 days of regrowth,without *** Findings The drought experiment revealed a phenotypic differentiation to drought in 30 *** populations,suggesting adaptive differentiation:the eastern seedlings showed the highest survival rate.A tradeoff between growth and survival was highlighted:the highest drought survival rate was associated with the lowest leaf elongation rate under non-limiting water ***

关键词： Epichloëfestucae water stress cutting fitness native grass mutualism

Evaluation of suprachiasmatic nucleus in Alzheimer’s disease with non-invasive magnetic resonance methods

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Neural Regeneration Research 2022年第8期17卷 1753-1754页

作者： rico singer A.Alia Leiden Institute of Chemistry Leiden UniversityLeidenThe Netherlands Institute of Medical Physics and Biophysics University of LeipzigLeipzigGermany

The suprachiasmatic nucleus and Alzheimer’s disease(AD):AD is the most frequently diagnosed form of dementia,with the total number of AD patients worldwide expected to triple by 2050 compared to 2015(Prince et al.,2015).Despite years of research,much of the AD pathology remains unclear with no treatment or cure *** its two hallmarks,amyloid-β(Aβ)plagues and hyperphosphorylated tau tangles,a distortion of circadian rhythms is commonly ***,poor sleep quality or trouble falling asleep are common AD symptoms,sometimes developing 10-15 years before cognitive symptoms associated with AD(Ju et al.,2014).

关键词： al. Alzheimer supra