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Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

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Neural Regeneration Research 2024年第9期19卷 2057-2067页

作者： Bismark Gatica-Garcia Michael J.Bannon Irma Alicia Martínez-Dávila Luis O.Soto-Rojas David Reyes-Corona Lourdes Escobedo Minerva Maldonado-Berny ME Gutierrez-Castillo Armando J.Espadas-Alvarez Manuel A.Fernandez-Parrilla Juan U.Mascotte-Cruz CP Rodríguez-Oviedo Irais E.Valenzuela-Arzeta Claudia Luna-Herrera Francisco E.Lopez-Salas Jaime Santoyo-Salazar Daniel Martinez-Fong departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico department of Pharmacology Wayne State University School of MedicineDetroitMIUSA Laboratorio de Patogénesis Molecular Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Red de Medicina para la Educación y desarrollo y la Investigación Científica de Iztacala(Red MEDICI) Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Nanoparticle Therapy Institute AguascalientesMéxico departamento de Biociencias e Ingeniería Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y DesarrolloInstituto Politécnico NacionalCiudad de MéxicoMéxico Escuela Nacional de Medicina y Homeopatía Instituto Politécnico NacionalCiudad de MéxicoMéxico departamento de Fisiología Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalCiudad de MéxicoMéxico departamento de biología Molecular y Biotecnología Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoMéxico departamento de Física Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico programa de Nanociencias y Nanotecnología Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate t

关键词： A1 astrocytes A2 astrocytes gene therapy microglia motor deficits nanoparticles neurodegeneration neuroinflammation senescence α-synuclein aggregates

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Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

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Neural Regeneration Research 2024年第2期19卷 289-295页

作者： Dina Medina-Vera Antonio Jesús López-Gambero Juan Antonio Navarro Carlos Sanjuan Elena Baixeras Juan decara Fernando Rodríguez de Fonseca Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND UGC Salud MentalMálagaSpain Facultad de Ciencias Universidad de MálagaMálagaSpain CIBER Enfermedades Cardiovasculares(CIBERCV) Hospital Universitario Virgen de la VictoriaUGC del CorazónMálagaSpain University of Bordeaux INSERMNeurocentre MagendieBordeauxFrance Euronutra S.L.Calle Johannes Kepler MálagaSpain departamento de Bioquímica y biología Molecular Facultad de MedicinaUniversidad de MálagaMálagaSpain

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

关键词： Alzheimer’s disease cyclin-dependent kinase 5 diabetes D-Pinitol inositols insulin resistance kinases phosphorylation PI3K/Akt tau

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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 system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The 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 results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We 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 pathways.While 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 outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Dietary carbohydrate-to-protein ratio influences growth performance,hepatic health and dynamic of gut microbiota in atlantic salmon(Salmo salar)

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Animal Nutrition 2022年第3期10卷 261-279页

作者： Alejandro Villasante Carolina Ramírez Hector Rodríguez Patricio Dantagnan Adrian Hernandez Elías Figueroa Jaime Romero Facultad de Medicina Veterinaria y Agronomía Universidad de Las AmericasSantiagoChile Laboratorio de Biotecnología de Alimentos Unidad de AlimentosInstituto de Nutricion y Tecnología de Los Alimentos(INTA)Universidad de ChileSantiagoChile Programa de Anatomía y Biología Del Desarrollo Facultad de MedicinaUniversidad de ChileSantiagoChile Núcleo de Investigacion en Produccion Alimentaria Facultad de Recursos NaturalesUniversidad Catolica de TemucoTemucoChile

Atlantic salmon(Salmo salar)fed a carbohydrate-rich diet exhibit suboptimal growth performance,along with other metabolic disturbances.It is well known that gut microbes play a pivotal role in influencing metabolism of the host,and these microbes can be modified by the diet.The main goal of the present study was to determine the effect of feeding graded levels of digestible carbohydrates to Atlantic salmon on the distal intestine digesta microbiota at 3 sampling times(i.e.,weeks 4,8 and 12),during a 12-week trial.A low carbohydrate-to-high protein diet(LC/HP,0%wheat starch),a medium carbohydrate-tomedium protein diet(MC/MP,15%wheat starch)or a high carbohydrate-to-low protein diet(HC/LP,30%wheat starch)was fed to triplicate fish tanks(27 to 28 fish per tank).We performed an in-depth characterization of the distal intestine digesta microbiota.Further,growth parameters,liver histology and the expression of genes involved in hepatic neolipogenesis in fish were measured.Fish fed a HC/LP diet showed greater hepatosomatic and viscerosomatic indexes(P=0.026 and P=0.018,respectively),lower final weight(P=0.005),weight gain(P=0.003),feed efficiency(P=0.033)and growth rate(P=0.003)compared with fish fed the LC/HP diet.Further,feeding salmon a high digestible carbohydrate diet caused greater lipid vacuolization,steatosis index(P=0.007)and expression of fatty acid synthase(fas)and delta-6 fatty acyl desaturase(d6fad)(P=0.001 and P=0.001,respectively)in the liver compared with fish fed the LC/HP diet.Although,the major impact of feeding a carbohydrate-rich diet to Atlantic salmon in beta diversity of distal intestine digesta microbiota was observed at week 4(HC/LP vs MC/MP and HC/LP vs LC/HP;P=0.007 and P=0.008,respectively)and week 8(HC/LP vs MC/MP;P=0.04),no differences between experimental groups were detected after 12 weeks of feeding.Finally,at the end of the trial,there was a negative correlation between lactic acid bacteria(LAB)members,including Leuconostoc and Lactobacillus,with hepatic steatosis level,the hepatosomat

关键词： Microbiota Microbiome Atlantic salmon Steatosis Lactic acid bacteria Probiotics

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Driving factors behind multiple populations

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Science China(Physics,Mechanics & Astronomy) 2024年第5期67卷 172-181页

作者： Ruoyun Huang Baitian Tang Chengyuan Li Doug Geisler Mario Mateo ying-yi Song Holger Baumgardt Julio A.Carballo-Bello yue Wang Jundan Nie Bruno Dias JoséG.Fernández-Trincado School of Physics and Astronomy Sun Yat-sen UniversityZhuhai 519082China CSST Science Center for the Guangdong-Hong Kong-Macao Greater Bay Area Zhuhai 519082China departamento de Astronomía Universidad de ConcepcionConcepcionChile Instituto de Investigación Multidisciplinario en Ciencia y Tecnología Universidad de La SerenaLa SerenaChile departamento de Astronomía Facultad de CienciasUniversidad de La SerenaChile department of Astronomy University of MichiganAnn Arbor 48109USA David A.Dunlap department of Astronomy&Astrophysics University of TorontoToronto ON M5S 3H4Canada Dunlap Institute for Astronomy&Astrophysics University of TorontoToronto ON M5S 3H4Canada School of Mathematics and Physics The University of QueenslandSt.Lucia QLD 4072Australia Instituto de Alta Investigación Universidad de TarapacáAricaChile CAS Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China Instituto de Astrofísica Departamento de Ciencias FísicasFacultad de Ciencias ExactasUniversidad Andres BelloSantiagoChile Instituto de Astronomía Universidad Católica del NorteAntofagastaChile

Star clusters were historically considered simple stellar populations,with all stars sharing the same age and initial chemical composition.However,the presence of chemical anomalies in globular clusters(GCs),called multiple stellar populations(MPs),has challenged star formation theories in dense environments.Literature studies show that mass,metallicity,and age are likely controlling parameters for the manifestation of MPs.Identifying the limit between clusters with/without MPs in physical parameter space is crucial to reveal the driving mechanism behind their presence.In this study,we look for MP signals in Whiting 1,which is traditionally considered a young GC.Using the Magellan telescope,we obtained low-resolution spectra withinλλ=3850-5500?for eight giants of Whiting 1.We measured the C and N abundances from the CN and CH spectral indices.C and N abundances have variations comparable with their measurement errors(~0.1 dex),suggesting that MPs are absent from Whiting 1.Combining these findings with literature studies,we propose a limit in the metallicity vs.cluster compactness index parameter space,which relatively clearly separates star clusters with/without MPs(GCs/open clusters).This limit is physically motivated.On a larger scale,the galactic environment determines cluster compactness and metallicity,leading to metal-rich,diffuse,old clusters formed ex situ.Our proposed limit also impacts our understanding of the formation of the Sagittarius dwarf galaxy:star clusters formed after the first starburst(age≤8-10 Gyr).These clusters are simple stellar populations because the enriched galactic environment is no longer suitable for MP formation.

关键词： stellar galactic galaxy

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Cerebral dopamine neurotrophic factor transfection in dopamine neurons using neurotensin-polyplex nanoparticles reverses 6-hydroxydopamine-induced nigrostriatal neurodegeneration

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Neural Regeneration Research 2022年第4期17卷 854-866页

作者： Manuel A.Fernandez-Parrilla David Reyes-Corona yazmin M.Flores-Martinez Rasajna Nadella Michael J.Bannon Lourdes Escobedo Minerva Maldonado-Berny Jaime Santoyo-Salazar Luis O.Soto-Rojas Claudia Luna-Herrera Jose Ayala-Davila Juan A.Gonzalez-Barrios Gonzalo Flores Maria E.Gutierrez-Castillo Armando JEspadas-Alvarez Irma A.Martínez-Dávila Porfirio Nava Daniel Martinez-Fong departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico programa Institucional de Biomedicina Molecular Escuela Nacional de Medicina y HomeopatíaInstituto Politécnico NacionalCiudad de MéxicoMéxico department of Biosciences IIIT-SrikakulamRajiv Gandhi University of Knowledge Technologies(RGUKT)Andhra PradeshIndia department of Pharmacology Wayne State University School of MedicineDetroitMIUSA departamento de Física Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Facultad de Estudios Superiores Iztacala Universidad Nacional Autónoma de MéxicoTlalnepantla de BazEdo.de MéxicoMéxico departamento de Fisiología Escuela Nacional de Ciencias BiológicasCiudad de MéxicoMéxico Laboratorio de Medicina Genómica Hospital Regional“1°de Octubre”ISSSTECiudad de MéxicoMéxico Laboratorio de Neuropsiquiatría Instituto de FisiologíaBenemérita Universidad Autónoma de PueblaPueblaPueblaMéxico departamento de Biociencias e Ingeniería Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y DesarrolloInstituto Politécnico NacionalCiudad de MéxicoMéxico programa de Nanociencias y nanotecnología Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico

Overexpression of neurotrophic factors in nigral dopamine neurons is a promising approach to reverse neurodegeneration of the nigrostriatal dopamine system,a hallmark in Parkinson's disease.The human cerebral dopamine neurotrophic factor(h CDNF)has recently emerged as a strong candidate for Parkinson's disease therapy.This study shows that h CDNF expression in dopamine neurons using the neurotensinpolyplex nanoparticle system reverses 6-hydroxydopamine-induced morphological,biochemical,and behavioral alterations.Three independent electron microscopy techniques showed that the neurotensin-polyplex nanoparticles containing the h CDNF gene,ranging in size from 20 to 150 nm,enabled the expression of a secretable h CDNF in vitro.Their injection in the substantia nigra compacta on day 21 after the 6-hydroxydopamine lesion resulted in detectable h CDNF in dopamine neurons,whose levels remained constant throughout the study in the substantia nigra compacta and striatum.Compared with the lesioned group,tyrosine hydroxylase-positive(TH^(+))nigral cell population and TH+fiber density rose in the substantia nigra compacta and striatum after h CDNF transfection.An increase inβIII-tubulin and growth-associated protein 43 phospho-S41(GAP43 p)followed TH^(+)cell recovery,as well as dopamine and its catabolite levels.Partial reversal(80%)of drugactivated circling behavior and full recovery of spontaneous motor and non-motor behavior were achieved.Brain-derived neurotrophic factor recovery in dopamine neurons that also occurred suggests its participation in the neurotrophic effects.These findings support the potential of nanoparticle-mediated h CDNF gene delivery to develop a disease-modifying treatment against Parkinson's disease.The Institutional Animal Care and Use Committee of Centro de Investigación y de Estudios Avanzados approved our experimental procedures for animal use(authorization No.162-15)on June 9,2019.

关键词： axonal growth brain-derived neurotrophic factor gene delivery nanoparticles neuritogenesis neuronal cytoskeleton neuroregeneration neurorestoration neurotrophic therapy Parkinson's disease reinnervation substantia nigra

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Auxin signaling gets oxidative to promote root hair growth

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Molecular Plant 2024年第5期17卷 696-698页

作者： Victoria Berdion Gabarain Miguel A.Ibeas Hernan Salinas-Grenet Jose M.Estevez Fundación Instituto Leloir&IIBBA-CONICET Av.Patricias Argentinas 435Buenos Aires C1405BWEArgentina Centro de Biotecnología Vegetal Facultad de Ciencias de la VidaUniversidad Andres BelloSantiagoChile ANID Millennium Science Initiative ProgramMillennium Nucleus for the Development of Super Adaptable Plants(MN-SAP)SantiagoChile ANID Millennium Science Initiative ProgramMillennium Institute for Integrative Biology(iBio)SantiagoChile

Root hairs(RHs)emerge as cylindrical cell protrusions from the root epidermis in a polar manner,and these outgrows increase the rhizosphere space to acquire water and nutrients,anchor the plant,and interact with various soil microorganisms.Auxin is one of the key hormones to promote RH growth,and high levels of auxin are directly promoted by low levels of macronutrients in the soil,such as phosphate(Bhosale et al.,2018)and nitrates(Jia et al.,2023).The nutritional signals for roots,which rapidly change in both time and place within the soil,are tightly linked to signaling pathways that execute swifts on cellular processes to adjust to a challenging environment.Plant rapid alkalinization factors(RALFs)are peptides that are released outside the cell and act as peptide-hormone signals.They attach to the extracellular domains of members of the Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE family,specifically FERONIA(FER)in conjunction with its co-receptor LORELEI-LIKE-GPIANCHORED PROTEIN 1.

关键词： soil outside alkali

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Mutated trimeric RBD vaccines:a platform against variants of concern

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2038-2040页

作者： Belén Aparicio Juan J.Lasarte Pablo Sarobe programa de Inmunología e Inmunoterapia Centro de Investigación Médica Aplicada(CIMACCUN)Universidad de NavarraPamplona31008Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBEREHD) Pamplona31008Spain IdiSNA Instituto de Investigación Sanitaria de NavarraPamplona31008Spain

He et al.recently reported in Nature Communications1 the development of a protein vaccine against SASR-CoV-2 Omicron variant consisting of a trimer of the spike protein receptor-binding domain(RBD)of the delta variant fused to heptad-repeat sequences 1 and 2.This vaccine induced broad-spectrum neutralizing antibodies and fully protected mice and non-human primates against challenge with live delta and Omicron virus.

关键词： vaccine vaccines

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Food-derived peptides with inhibitory capacity for HMG-CoA reductase activity: a potential nutraceutical for hypercholesterolemia

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Food Science and Human Wellness 2023年

作者： Guillermo Santos-Sánchez Ana Isabel álvarez-López Eduardo Ponce-Espa?a Patricia Judith Lardone Antonio Carrillo-Vico Ivan Cruz-Chamorro Instituto de Biomedicina de Sevilla IBiS (Universidad de Sevilla HUVR Junta de Andalucía CSIC) departamento de Bioquímica Médica y biología Molecular e Inmunología Universidad de Sevilla

Cardiovascular diseases (CVDs) are the leading global cause of mortality and disease burden. Statins are the most prescribed lipid-lowering drugs to treat hypercholesterolemia and prevent CVDs. The biochemical mechanism of statins consists of competitive inhibition of the 3-hydroxy-3-methylglutaryl-CoA reductase enzyme (HMG-CoAR)， the limiting enzyme in cholesterol biosynthesis. Due to statin intolerance in some patient groups， the search for new inhibitors is a field of great interest. This review focusses on the studies reporting the inhibitory effect of protein hydrolysates and biopeptides on the HMG-CoAR enzyme activity. The analysis of the action mechanism and physicochemical characteristics of the HMG-CoAR inhibitory peptides revealed that the molecular weight， amino acid composition， charge， and polarity are key aspects of the interaction with the HMG-CoAR enzyme. In conclusion， this review reveals the potential of using food peptides as new cholesterol-lowering agents and opens a new interesting field of research. However， clinical approaches are mandatory to confirm their therapeutic hypercholesterolemic effect.

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The tip of the iceberg:ROP2 directly interacts with SyP121 to regulate root-hair polarization,elongation,and exocytosis

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Molecular Plant 2022年第7期15卷 1084-1086页

作者： Martiniano M.Ricardi Jose M.Estevez Instituto de Fisiología Biología Molecular y Neurociencias(IFIBYNE-UBA-CONICET)and Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresCiudad UniversitariaBuenos Aires C1428EHAArgentina Fundación Instituto Leloir and IIBBA-CONICET.Av.Patricias Argentinas 435 Buenos Aires C1405BWEArgentina Centro de Biotecnología Vegetal Facultad de Ciencias de la VidaUniversidad Andres BelloSantiago 8370146Chile ANID-Millennium Science Initiative Program-Millennium Nucleus for the development of Super Adaptable Plants(MN-SAP) Santiago 8370146Chile

Root hairs(RHs)grow in a polar manner as cylindrical protrusions from the root epidermis.They significantly expand the root volume in the rhizosphere to search for water and nutrients,anchor the plant,and promote interactions with several kinds of microorganisms in the soil.Trichoblasts,the epidermis cell type responsible for RH development,switch from anisotropic cell elongation to tip growth through polarization of the growth machinery to a predefined RH initiation domain(RHID)at the plasma membrane.

关键词： tip polarization cylindrical

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