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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

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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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Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri H.Juárez Adalberto Merighi Department of Veterinary Sciences University of TurinGrugliascoTOItaly Department of psychiatry and Neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC *** increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

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Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María portela-Lomba paloma Sobrado-Calvo Diana Simón Johnny Di pierdomenico Alejandro Gallego-Ortega Mar pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

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Ursane derivatives isolated from leaves of Hylocereus undatus inhibit glycation at multiple stages

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Chinese Journal of Natural Medicines 2018年第11期16卷 856-865页

作者： rosa MARTHA pérez-Gutiérrez SUSANA GABRIELA Enriquez-Alvirde Research Laboratory of Natural products School of Chemical Engineering and Extractive Industries National Polytechnic Institute

The present study was designed to evaluate the therapeutic potential of bioactive compounds from chloroform extract of the leaves of Hylocereus undatus in the formation of advanced glycation end products(AGEs) in vitro. Bioactivity-guided fractionation of chloroform extract from Hylocereus undatus afforded two novel 12-ursen-type triterpenes, 3β, 16α, 23-trihydroxy-urs-12-en-28-oic acid(1) and 3β, 6β, 19α, 22α-tetrahydroxy-urs-12-en-28-oic acid(2), as well as four known triterpenes 2α, 3β, 23-tetrahydroxy-urs-11-en-28-oic acid(3), 3β-acetoxy-28-hydroxyolean-12-ene(4), 3β, 16α-dihidroxyolean-12-ene(5) and 3β-acetoxy-olean-12-ene(6). Our results revealed that triterpenes 1–3 were able to inhibit the formation of AGEs in all tested assays. The data indicated that the triterpenes had inhibitory activity at the múltiple stages of glycation and that there might be a high potential for decreasing protein oxidation and protein glycation that can enhance glycative stress in diabetic complications.

关键词： Hylocereus undatus Advanced glycation end product Triterpenes

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Anchor Root Development: A World within Worlds

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Molecular plant 2020年第8期13卷 1105-1107页

作者： JoséManuel pérez-pérez Instituto de Bioingeniería Universidad Miguel Hernández03202 ElcheSpain

Many plant species develop shoot-borne adventitious roots(ARs)with specialized functions that contribute to plant adaptability by enhancing resource capture and stress *** Arabidopsis,as in many dicots,the postembryonic root system is primarily composed of lateral roots(LRs),which originate from the xylem pole pericycle cells through a process that involves periodic oscillation in gene expression mediated by a β-carotenoidderived signal(Dickinson et al.,2019).Our understanding of the key molecular and signaling events regulating AR initiation has recently been obtained from studies in Arabidopsis,where ARs are formed on etiolated hypocotyls upon transfer to light(Lakehal et al.,2019)or from excised leaf explants(Zhang et al.,2019).Anchor roots(ANRs)are a type of AR that originate immediately below the root-hypocotyl junction in an auxindependent manner and that require a diapocarotenoid-derived signal(anchorene)to emerge(Jia et al.,2019).ANR primordia activation may represent a generic mechanism to compensate for the loss of the growth potential of the primary root(pR),as it is enhanced by mutations affecting pR growth,by whole-root excision or by nitrogen deficiency(Jia et al.,2019).A recent paper by Bai et al.(2020)provides direct evidence that a regulatory module involving the Ap2/ERF transcription factor ABSCISIC ACID INSENSITIVE 4(ABI4),the mitogen-activated protein kinases(MApKs)MpK3 and MpK6,and the phosphatase pp2C12 controls ANR emergence in Arabidopsis.

关键词： roots Arabidopsis Root

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Incipient sliding of adhesive contacts

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Friction 2022年第6期10卷 963-976页

作者： Francesc pÉrez-RÀFOLS Lucia NICOLA Department of Industrial Engineering University of PadovaPadua I-35131Italy Department of Material Science and Engineering Delft University of TechnologyDelft 2628 CN the Netherlands

A model is proposed herein to investigate the incipient sliding of contacts in the presence of both friction and adhesion,where the interfacial response is modeled based on traction-separation laws.A Maugis-like parameter is defined to characterize the response in the tangential ***,the model is used to investigate the contact between a smooth cylinder and a flat body,where adhesion-friction interactions are strong.A range of behaviors are observed when a tangential displacement is imposed:When the parameter is low,the contact pressure exhibits a relatively constant profile;when it is high,a pressure spike is observed at the edge of the *** difference is caused by a significant interface compliance in the former case,which limits the amount of *** results for the mid-range values of the Maugis-like parameter can qualitatively replicate various experiments performed using polydimethylsiloxane(pDMS)balls.

关键词： incipient sliding adhesion traction-separation laws

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presynaptic endoplasmic reticulum architecture and hereditary spastic paraplegia

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Neural Regeneration Research 2024年第3期19卷 485-486页

作者： Juan Josépérez-Moreno Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevillaand Departamento de Biología CelularFacultad de BiologíaUniversidad de SevillaSevilleSpain

Hereditary spastic paraplegia(HSp)is a clinically and genetically heterogeneous neurodegenerative disorder,characterized primarily by progressive spasticity and weakness in the lower *** ients can also experience peripheral neuropathy,cognitive impairment,and other neurological *** date,more than 80 genes have been implicated in HSp,encompassing various cellular components,although mutations in genes encoding endoplasmic reticulum(ER)-shaping proteins are the most prevalent(parodi et al.,2017).ER-shaping proteins are generally known for regulating the tubulation and curvation of the ER,but most of them show additional functions,including fusion of ER tubules,microtubule-severing,ER autophagy,lipid droplet synthesis,contact sites with other organelles(Öztürk et al.,2020).This highlights the complexity of studying the role of these proteins and the link between ER function and HSp.

关键词： reticulum endoplasmic

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Long-term outcomes after stenting as a"bridge to surgery"for the management of acute obstruction secondary tocolorectal cancer

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World Journal of Gastrointestinal Oncology 2016年第1期8卷 105-112页

作者： javier suárez javier jimenez-pérez department of general surgery coloproctology unitcomplejo hospitalario de navarra31008 PamplonaSpain department of gastroenterology endoscopy unithospital de la ribera46600 AlziraSpain

Obstructive symptoms are present in 8% of cases at the time of initial diagnosis in cases of colorectal cancer. Emergency surgery has been classically considered the treatment of choice in these patients. However, in the majority of studies, emergency colorectal surgery is burdened with higher morbidity and mortality rates than elective surgery, and many patients require temporal colostomy which deteriorates their quality of life and becomes permanent in 10%-40% of cases. The aim of stenting by-pass to surgery is to transform emergency surgery into elective surgery in order to improve surgical results, obtain an accurate tumoral staging and detection of synchronous lesions, stabilization of comorbidities and performance of laparoscopic surgery. Immediate results were more favourable in patients who were stented concerning primary anastomosis, permanent stoma, wound infection and overall morbidity, having the higher surgical risk patients the greater benefit. However, some findings laid out the possible implication of stenting in long-term results of oncologic treatment. perforation after stenting is related to tumoral recurrence. In studies with perforation rates above 8%, higher recurrences rates in young patients and lower disease free survival have been shown. On the other hand, after stenting the number of removed lymph nodes in the surgical specimen is larger, patients can receive adjuvant chemotherapy earlier and in a greater percentage and the number of patients who can be surgically treated with laparoscopic surgery is larger. Finally, there are no consistent studies able to demonstrate that one strategy is superior to the other in terms of oncologic benefits. At present, it would seem wise to assume a higher initial complication rate in young patients without relevant comorbidities and to accept the risk of local recurrence in old patients(> 70 years) or with high surgical risk(ASA Ⅲ/Ⅳ).

关键词： Self-expanding metallic stent Colorectalcancer Obstructive colorectal cancer Colorectal cancerchemotherapy Colorectal cancer surgery

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Rehabilitation of degraded areas in northeastern patagonia, Argentina: Effects of environmental conditions and plant functional traits on performance of native woody species

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Journal of Arid Land 2020年第4期12卷 653-665页

作者： Juan M ZEBERIO Carolina A pÉrez National University of Río Negro Atlantic HeadquartersCenter for Environmental Studies from Norpatagonia(CEANPa)Viedma 8500Argentina National Council of Scientific and Technical Research(CONICET) Viedma 8500Argentina Ecological and Environmental Systems Research Laboratory(LISEA) National University of La PlataLa Plata 1900Argentina

Degradation processes affect a vast area of arid and semi-arid lands around the world and damage the environment and people′s health. Degradation processes are driven by human productive activities that cause direct and indirect effects on natural resources, such as species extinction at regional scale, reduction and elimination of vegetation cover, soil erosion, etc. In this context, ecological rehabilitation is an important tool to recover key aspects of the degraded ecosystem. Rehabilitation trials rely on the use of native plant species with characteristics that allow them to obtain high survival and growth rates. The aim of this work was to assess the survival and growth of native woody species in degraded areas of northeastern patagonia and relate them to plant functional traits and environmental variables. We observed high early and late survival rates, and growth rates in prosopis flexuosa DC. var. depressa F.A. Roig and Schinus johnstonii F.A. Barkley, and low values in Condalia microphylla Cav. and Geoffroea decorticans(Gillies ex Hook. & Arn.) Burkart. Early survival rates were positively associated with specific leaf area(SLA) and precipitation, but negatively associated with wood density, the maximum mean temperature of the warmest month and the minimum mean temperature of the coldest month. Late survival rates were positively associated with SLA and soil organic matter, but negatively associated with plant height and precipitation. The temperature had a positive effect on late survival rates once the plants overcame the critical period of the first summer after they were transplanted to the field. prosopis flexuosa and S. johnstonii were the most successful species in our study. This could be due to their functional traits that allow these species to acclimatize to the local environment. Further research should focus on C. microphylla and G. decorticans to determine how they relate to productive conditions, acclimation to environmental stress, auto-eco

关键词： arid lands Condalia microphylla Geoffroea decorticans prosopis flexuosa Schinus johnstonii survival rates height growth basal diameter growth

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