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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

Effect of Zn binding to phytate and humic substances on its uptake by wheat(Triticum durum l.)as affected by carbonates and Fe oxides

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Pedosphere 2022年第6期32卷 823-832页

作者： ana M.GARCÍA-l.pez Ramiro RECENA Antonio DElGADO Department of Agronomy ETSIAUniversity of SevilleSeville 41013(Spain)

Although complexation with soil organic matter may improve zinc(Zn)bioavailability to plants,the effect of Zn sorbent surface on the use of complexed Zn by plants remains *** objective of this research was to elucidate how Zn complexation with humic substances(HS)and phytate affects the uptake of Zn by wheat plants depending on the main sorbent surface in growth media,i.e.,carbonates and Fe *** this end,two pot experiments were performed,one using Fe oxide-coated siliceous as the siliceous growth medium sand and the other using a mixture of calcareous sand and siliceous sand as the calcareous growth *** experiment involved three Zn sources,Zn-HS complex,Zn phytate,and ZnSO_(4).All sources were applied with surface irrigation at two Zn rates(0.25 and 2 mg kg^(-1) growth medium).The Zn-HS complex significantly increased Zn uptake by plants in both media,relative to the other two Zn sources,but no significant difference was observed between Zn phytate and ZnSO_(4).In the calcareous medium,Zn-HS complex and Zn phytate resulted in significantly higher dry biomass yields of wheat than ZnSO_(4).In the siliceous medium,spike and shoot dry biomass yields with Zn-HS complex at the low rate and Zn phytate at both rates were not significantly different from those with ZnSO_(4) at the high *** harvest,approximately 50%of the Zn applied as Zn-HS complex remained extractable by diethylenetriaminepentaacetic acid(DTPA),while this proportion was less than 20%for the other Zn ***,Zn-HS complex and Zn phytate are sources of available Zn for plants,and they are more effective than ZnSO_(4) in increasing plant growth,particularly when carbonates are the main Zn sorbent surface.

关键词： calcareous growth medium micronutrient organic matter organic phosphorus Zn availability Zn deficiency Zn sorbent surface Zn source

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)

In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions

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Acta Pharmaceutica Sinica B 2021年第4期11卷 989-1002页

作者： ana lMartínez-l.pez Carlos JGonzález-Navarro Paula Aranaz JosélVizmanos Juan MIrache NANO-VAC Research Group Department of Chemistry and Pharmaceutical TechnologySchool of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Center for Nutrition Research School of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Department of Biochemistry&Genetics School of ScienceUniversity of NavarraPamplona 31080Spain Navarra Institute for Health Research(IdiSNA) Pamplona 31080Spain

The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of *** nanocarriers,based on the coating of zein nanoparticles with a polymer conjugate containing PEG,displayed a size of 260 nm with a negative surface charge and an insulin payload of 77 mg/*** intestinal pig mucus,the diffusivity of these nanoparticles(PPA-NPs)was found to be 20-fold higher than bare nanoparticles(NPs).These results were in line with the biodistribution study in rats,in which NPs remained trapped in the mucus,whereas PPA-NPs were able to cross this layer and reach the epithelium *** therapeutic effcacy was evaluated in Caenorhabditis elegans grown under high glucose *** this model,worms treated with insulin-loaded in PPA-NPs displayed a longer lifespan than those treated with insulin free or nanoencapsulated in *** finding was associated with a signifcant reduction in the formation of reactive oxygen species(ROS)as well as an important decrease in the glucose and fat content in *** effects would be related with the mucus-permeating ability of PPA-NPs that would facilitate the passage through the intestinal peritrophic-like dense layer of worms(similar to mucus)and,thus,the absorption of insulin.

关键词： Nanoparticles Oral delivery Mucus-permeating Biodistribution Insulin Caenorhabditis elegans ROS

Amyotrophic lateral sclerosis: a complex syndrome that needs an integrated research approach

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Neural Regeneration Research 2019年第2期14卷 193-196页

作者： Javier Riancho Francisco J.Gil-Bea ana Santurtun Adolfo l.pez de Munaín Service of Neurology Hospital Sierrallana-Idival CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases Ministry of Economy and Competitiveness Institute Carlos Ⅲ) Neurosciences Area Institute Biodonostia Department of Physiology and Pharmacology University of Cantabria-Idival Department of Neurology University Hospital Donostia Department of Neurosciences University of the Basque Country Universidad País Vasco-Euskal Herria Unibertsitatea

Amyotrophic lateral sclerosis, the most common neurodegenerative disease affecting motor neurons, lacks an effective treatment. A small fraction of amyotrophic lateral sclerosis cases have a familial origin, related to mutations in causative genes, while the vast majority of amyotrophic lateral sclerosis cases are considered to be sporadic, resulting from the interaction between genes and environmental factors in predisposed individuals. During the past few years, dozens of drugs have been postulated as promising strategies for the disease after showing some beneficial effects in preclinical cellular and murine models. However, the translation into clinical practice has been largely unsuccessful and the compounds failed when were tested in clinical trials. This might be explained, at least partially, by the enormous complexity of the disease both from clinico-epidemiological and a pathogenic points of view. In this review, we will briefly comment on the complexity of the disease focusing on some recent findings, and we will suggest how amyotrophic lateral sclerosis research might be reoriented to foster the advance in the diagnostic and therapeutic questions.

关键词： amyotrophic lateral sclerosis AlS environment epidemiology genes phenotype therapy

PtRu nanoparticles supported on noble carbons for ethanol electrooxidation

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Journal of Energy Chemistry 2022年第3期31卷 168-180,I0006页

作者： Alberto Rodríguez-Gómez Enrico lepre luz Sánchez-Silva Nieves l.pez-Salas ana Raquel de la Osa Faculty of Chemical Sciences and Technologies University of Castilla-La ManchaEnrique Costa Novella Building.Avda.Camilo Jose Cela1213071 Ciudad RealSpain Colloid Chemistry Department Max Planck Institute of Colloids and InterfacesAm Mühlenberg 114476 PotsdamGermany

In this work,three cytosine derived nitrogen doped carbonaceous materials(noble carbons,NCs)with different atomic C/N ratios and porous networks have been synthesized and used as supports for Pt Ru electrocatalysts in the ethanol oxidation reaction(EOR)for clean hydrogen ***,the metal phase and the carbon support play critical roles in the electrocatalysts final *** NPs size distribution was obtained over supports with low atomic C/N ratios(i.e.,4 and 6)and defined porosity(i.e.,1701 m^(2)g^(-1)for Pt Ru/CNZ and 1834 m^(2)g^(-1)for Pt Ru/ClZ,respectively).In contrast,a lower C/N ratio and poor porous network(i.e.,65 m^(2)g^(-1),Pt Ru/ClK)led to the largest particle size and fostered an increase of the alloying degree between Pt and Ru NPs(i.e.,3%for C/N~6 and 28%for C/N~3).Electrochemical active surface area was found to increase with decreasing NPs size and the alloy extent,due to a higher availability of Pt active *** degradation tests showed that Pt Ru/NCs outperform similar to Pt Ru NPs on commercial carbon pointing at the stabilizing effect of *** Ru/CNZ exhibited the best electrochemical performance(i.e.,69.1 m A mgPt-1),outperforming Pt Ru/ClZ and Pt Ru/ClK by3-and 9-fold,respectively,due to a suitable compromise between particle sizes,degree of alloy,textural properties and elemental *** anodes were scaled-up to a proton exchange membrane cell and Pt Ru/CNZ was proved to provide the best electrocatalytic activity(262 m A cm^(-2)and low energy requirements),matching the values obtained by the state of the art of EOR electrocatalysts.

关键词： Noble carbon Cytosine H2 production Ethanol electrooxidation PtRu anode PEM cell

Multifunctional antimicrobial chlorhexidine polymers by remote plasma assisted vacuum deposition

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Frontiers of Chemical Science and Engineering 2019年第2期13卷 330-339页

作者： ana Mora-Boza Francisco J.Aparicio Maria Alcaire Carmen l.pez-Santos Juan P.Espinós Daniel Torres-lagares ana Borrás Angel Barranco Consejo Superior de Investigaciones Cientificas. Instituto de Ciencia de Materiales de Sevilla (CSIC-Universidad de Sevilla) c/Americo Vespucio 49 41092 SevillaSpain Facultad de Odontologia Universidad de Sevilla (USE) c/Avicena41009 SevillaSpain

Novel antibacterial materials for implants and medical instruments are essential to develop practical strategies to stop the spread of healthcare associated infections. This study presents the synthesis of multifunctional antibacterial nanocoatings on polydimethylsiloxane (PDMS) by remote plasma assisted deposition of sublimated chlorhexidine powders at low pressure and room temperature. The obtained materials present effective antibacterial activity against Escherichia coli K12, either by contact killing and antibacterial adhesion or by biocide agents release depending on the synthetic parameters. In addition, these multifunctional coatings allow the endure hydrophilization of the hydrophobic PDMS surface, thereby improving their biocompatibility. Importantly, cell-viability tests conducted on these materials also prove their non-cytotoxicity, opening a way for the integration of this type of functional plasma films in biomedical devices.

关键词： plasma polymers conformal plasma deposition chlorhexidine bactericide PDMS biocompatibility

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-l.pez 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

Prevalence of hepatocarcinoma-related hepatitis B virus mutants in patients in grey zone of treatment

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World Journal of Gastroenterology 2019年第38期25卷 5883-5896页

作者： ana Isabel Gil-García Antonio Madejón Irene Francisco-Recuero ana l.pez-l.pez Emiliana Villafranca Miriam Romero Araceli García Antonio Olveira Rocío Mena Juan Ramón larrubia Javier García-Samaniego Hepatology Unit Hospital Universitario La PazMadrid 28046Spain Centro de Investigación Biomédica en Red Instituto de Salud Carlos IIIMadrid 28029Spain Instituto de Investigación del Hospital Universitario la Paz Madrid 28046Spain Biochemistry Department Faculty of MedicineUniversidad Autónoma de MadridMadrid 28029Spain Instituto de Genética Médica y Molecular Hospital Universitario La PazMadrid 28046Spain Translational Hepatology Unit Hospital General Universitario de GuadalajaraGuadalajara 19002Castilla-La ManchaSpain

BACKGROUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health *** this sense,the identification of HBV mutants related with an increased risk of hepatocellular carcinoma(HCC)could be useful to identify subpopulations with potential indication of antiviral *** To analyze the prevalence/persistence of hepatitis B virus(HBV)preS and basal core promoter(BCP)/precore/core variants associated to HCC development in CHB patients in the grey *** Work was designed as a longitudinal retrospective study,including 106 plasma samples from 31 patients with CHB in the grey zone of treatment:Hepatitis B e antigen negative,HBV-DNA levels between 12-20000 IU/ml,normal or discordant transaminase levels during follow up and mild/moderate necroinflammatory activity in liver biopsy or Fibroscan(up to 9.5 kPa).Serum HBVDNA was tested using the Abbott Real Time HBV Assay and the BCP/precore/core and the hepatitis B surface antigen(HBsAg)coding regions were analyzed in positive samples by PCR/bulk-sequencing to identify the HCCrelated HBV *** High-risk HCC related mutants were detected in 24(77%)patients:19(61%)in the BCP/precore/core,and 7(23%)in the HBsAg coding region(2 preS1 and 5 preS2 deletions).The prevalence of preS deletions was genotype-dependent:3/5(60%)patients with preS2 deletions and 1/2 with preS1 deletions were infected with the HBV-E *** HBV-E was the most prevalent in sub-Saharan patients,a correlation between preS deletions and ethnicity was also found:6/8(75%)sub-Saharan vs 1/19(5%)Caucasian patients had preS deletions(P=0.00016).Remarkably,this correlation was maintained in those patients infected with HBV-A,a minor genotype in sub-Saharan patients:2/2 patients infected with HBV-A from West Africa vs 0/6 of Caucasian origin had preS *** HCC related variants were the major strains and persisted over time(up to 48 mo).Pa

关键词： Hepatitis B virus Hepatocellular carcinoma PreS deletions Hepatitis B virus treatment Grey zone