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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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Neural Regeneration Research 2025年第7期20卷 1944-1956页

作者： Julia Castillo-González elena González-Rey Institute of Parasitology and Biomedicine lopez-Neyra(IPBlN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

Calcium-sensitive protein MlC1 as a possible modulator of the astrocyte functional state

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Neural Regeneration Research 2025年第7期20卷 2008-2010页

作者： elena Ambrosini Angela lanciotti maria Stefania Brignone Department of Neuroscience Istituto Superiore di SanitàRomeItaly

Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult *** maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.

关键词： alterations modulator maintain

Context-dependent role of sirtuin 2 in inflammation

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Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado elena Puerta Department of Pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health Research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NlRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NlRP3 nuclear factorκB sirtuin 2

Grasslands Response to livestock Grazing Intensity in the Austral Pampas(Argentina):Testing the Intermediate Disturbance Hypothesis

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Phyton-International Journal of Experimental Botany 2024年第8期93卷 2037-2050页

作者： Ana elena de Villalobos maría Andrea long Grupo de Investigación en Ecosistemas de Pastizal(GIEP) CERZOSCONICETBahía Blanca8000Argentina Departamento de Biología Bioquímica y FarmaciaUniversidad Nacional del SurBahía Blanca8000Argentina

livestock grazing has a significant impact on natural grasslands,with approximately one-third of the world’s land area dedicated to this *** 20%of global grasslands are highly degraded due to overgrazing,affecting their productivity and conservation *** practices are required to ensure sustainable livestock production that supports *** Intermediate Disturbance Hypothesis(IDH)suggests that environments with moderate levels of disturbance exhibit a higher species *** grazing can reduce the dominance of certain species,thereby enhancing plant ***,concerns arise regarding the increase of exotic and unpalatable species under moderate grazing levels,complicating grassland conservation *** impact of livestock grazing on the functional structure of grasslands depends on factors such as grazing intensity,livestock species,and environmental *** in grazing intensity may increase specific and functional diversity under moderate grazing,potentially masking the presence of invasive exotic *** the Austral Pampas(Pampean phytogeographic province,Buenos Aires,Argentina),grasslands face various pressures from domestic livestock grazing that endanger their integrity if not properly ***,our study aims to investigate potential differences in species richness and diversity,functional diversity,exotic plant abundance,and the number and distribution of plant functional groups across varying grazing *** IDH is utilized as a tool to regulate livestock pressure for grassland *** and functional diversity indices were used to assess the impact of grazing on grassland *** grazing increased species and functional diversity,while intensively grazed or ungrazed areas showed reduced *** presence influenced the balance between native and exotic plants,with ungrazed areas having higher native plant abundance and grazed areas exhibiti

关键词： Natural grasslands grazing effects disturbance specific and functional diversity

Determination of l-norvaline and l-tryptophan in dietary supplements by nano-lC using an O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11- dihydroquinidine-silica hybrid monolithic column

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Journal of Pharmaceutical Analysis 2020年第1期10卷 70-77页

作者： Dongsheng Xu elena Sanchez-lopez Qiqin Wang Zhengjin Jiang maría luisa marina Departamento de Química Analítica Química Física e Ingeniería QuímicaUniversidad de AlcalaCtra.Madrid-Barcelona Km.33.60028871Alcala de Henares(Madrid)Spain Institute of Pharmaceutical Analysis College of PharmacyJinan UniversityGuangzhou510632China Department of Pharmacy and Guangdong Province Key laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine&New Drug Research Jinan UniversityGuangzhou510632China Instituto de Investigacion Química“Andres M.del Río”(IQAR) Universidad de AlcalaCtra.Madrid-Barcelona Km.33.60028871Alcala de Henares(Madrid)Spain

An analytical methodology based on an O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine(MQD)-silica hybrid monolithic column was developed for the enantioseparation of 9-fluorenylmethoxycarbonyl(FMOC)derivatized amino acids by nano-liquid *** mobile phase was optimized including the apparent pH,content of ACN,and concentration of the buffer to obtain a satisfactory enantioresolution performance.27 FMOC derivatized amino acids including 19 protein and 8 non-protein amino acids were tested,and 19 out of them were enantiomerically discriminated obtaining baseline separation for 11 of *** characteristics of the method were evaluated for norvaline and tryptophan in terms of linearity,precision,accuracy,limits of detection(lOD)and quantitation(lOQ)showing good performance to be applied to the enantiomeric determination of these amino acids in dietary *** and lOQ values were 9.3 and 31 mM for norvaline enantiomers and 7.5 and 25 mM for tryptophan enantiomers,*** contents of D-norvaline and D-tryptophan were below their respective lODs in all the analyzed *** of l-tryptophan and l-norvaline showed good agreement with the labeled contents except for one sample which did not show presence of l-norvaline,contrary to the label indication.

关键词： 9-Fluorenylmethoxycarbonyl Amino acids Chiral separation Nano-lC Quinidine-silica hybrid monolithic column

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

Residual activity of cetrimide and chlorhexidine on Enterococcus faecalis-infected root canals

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International Journal of Oral Science 2014年第1期6卷 46-49页

作者： Carmen maría Ferrer-luque maría Teresa Arias-Moliz Matilde Ruíz-linares maría elena martínez García Pilar Baca Department of Stomatology School of Dentistry University of Granada Department of Microbiology School of Dentistry University of Granada

Effective final irrigation regimen is an important step in order to achieve better disinfection and ensure residual antimicrobial effects after root canal preparation. The aim of this study was to compare the residual antimicrobial activity of 0.2% cetrimide, and 0.2% and 2% chlorhexidine in root canals infected with Enterococcus faecalis. Biofilms of E. faecalis were grown on uniradicular roots for 4 weeks. After root canal preparation, root canals were irrigated with 17% ethylenediaminetetraacetic acid （EDTA） to remove the smear layer. The roots were randomly divided into three experimental groups （n=26） according to the final irrigating solution： Group I, 5 ml 0.2% cetrimide; Group II, 5 ml 0.2% chlorhexidine; and Group III, 5 ml 2% chlorhexidine. Samples were collected for 50 days to denote the presence of bacterial growth. The proportion of ungrown specimens over 50 days was evaluated using the nonparametric Kaplan-Meier survival analysis. Differences among groups were tested using the log-rank test and the level of statistical significance was set at P〈0.05. The highest survival value was found with 2% chlorhexidine, showing statistically significant differences from the other two groups. At 50 days, E. faecalisgrowth was detected in 69.23% specimens in Groups I and II, and in 34.61% specimens of Group III. There were no significant differences between 0.2% cetrimide and 0.2% chlorhexidine. Final irrigation with 2% chlorhexidine showed greater residual activity than 0.2% chlorhexidine and 0.2% cetrimide in root canals infected with E. faecalis.

关键词： antimicrobial effects biofilms cetrimide chlorhexidine Enterococcus faecalis final irrigation residual activity

Alexander disease:the road ahead

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Neural Regeneration Research 2023年第10期18卷 2156-2160页

作者： maría A.Pajares elena Hernández-Gerez Milos Pekny Dolores Pérez-Sala Department of Structural and Chemical Biology Centro de Investigaciones Biológicas Margarita SalasMadridSpain laboratory of Astrocyte Biology and CNS Regeneration Center for Brain RepairDepartment of Clinical NeuroscienceInstitute of Neuroscience and PhysiologySahlgrenska Academy at the University of GothenburgGothenburgSweden University of Newcastle NewcastleNSWand the Florey Institute of Neuroscience and Mental HealthParkvilleVICAustralia

Alexander disease is a rare neurodegenerative disorder caused by mutations in the glial fibrillary acidic protein,a type III intermediate filament protein expressed in *** early(infantile or juvenile)and adult onsets of the disease are known and,in both cases,astrocytes present characteristic aggregates,named Rosenthal *** are spread along the glial fibrillary acidic protein sequence disrupting the typical filament network in a dominant *** the presence of aggregates suggests a proteostasis problem of the mutant forms,this behavior is also observed when the expression of wild-type glial fibrillary acidic protein is ***,several isoforms of glial fibrillary acidic protein have been described to date,while the impact of the mutations on their expression and proportion has not been exhaustively ***,the posttranslational modification patterns and/or the protein-protein interaction networks of the glial fibrillary acidic protein mutants may be altered,leading to functional changes that may modify the morphology,positioning,and/or the function of several organelles,in turn,impairing astrocyte normal function and subsequently affecting *** particular,mitochondrial function,redox balance and susceptibility to oxidative stress may contribute to the derangement of glial fibrillary acidic protein mutant-expressing *** study the disease and to develop putative therapeutic strategies,several experimental models have been developed,a collection that is in constant *** fact that most cases of Alexander disease can be related to glial fibrillary acidic protein mutations,together with the availability of new and more relevant experimental models,holds promise for the design and assay of novel therapeutic strategies.

关键词： astrocytes endoplasmic reticulum stress glial fibrillary acidic protein mutants metabolism misassembly misfolding neurodegeneration oxidative stress posttranslational modifications unfolded protein response

Chiral carbon dots:synthesis,optical properties,and emerging applications

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light(Science & Applications) 2022年第4期11卷 542-564页

作者： Aaron Doring elena Ushakova Andrey l.Rogach Department of Materials Science and Engineering and Centre for Functional Photonics(CFP)City University of Hong Kong83 Tat Chee AvenueKowloonHong Kong SARChina. Center of Information Optical Technologies ITMO UniversitySaint Petersburg 197101Russia. Shenzhen Research Institute City University of Hong Kong518057 ShenzhenChina

Carbon dots are luminescent carbonaceous nanoparticles that can be endowed with chiral properties,making them particularly interesting for biomedical applications due to their low cytotoxicity and facile *** recent years,synthetic efforts leading to chiral carbon dots with other attractive optical properties such as two-photon absorption and circularly polarized light emission have *** start this review by introducing examples of molecular chirality and its origins and providing a summary of chiroptical spectroscopy used for its *** approaches used to induce chirality in nanomaterials are *** the main part of this review we focus on chiral carbon dots,introducing their fabrication techniques such as bottom-up and top-down chemical syntheses,their morphology,and optical/chiroptical *** then consider emerging applications of chiral carbon dots in sensing,bioimaging,and catalysis,and conclude this review with a summary and future challenges.

关键词： properties synthesis chiral