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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-p.rez 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 p.rez-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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Speed Control of a DC Motor by Using Fuzzy Variable Structure Controller

Speed Control of a DC Motor by Using Fuzzy Variable Structur...

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第二十七届中国控制会议

作者： p.rez claudia Strefezza Miguel Universidad Simón Bolívar Departamento de Procesosy Sistemas

ISBN: (纸本)9787900719706

Since DC motors are wide used in the industry,many applications control theory has been *** an alternative the following work presents the design of a fuzzy variable structure control for the speed control of a DC *** strategy control combines fuzzy and sliding mode control *** fuzzy rules are used for this *** parameters of the fuzzy controller are adjusted by using the VSC for a better response and *** simulations results with the control scheme presented here offer higher robustness and is easier to adjust compared with classical fuzzy controllers.

关键词： Fuzzy control Variable structure controller DC motor

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Efficacy of antimicrobials in preventing resistance in solid organ transplant recipients:A systematic review of clinical trials

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World Journal of Transplantation 2025年第1期15卷 156-164页

作者： Carlos M Ardila pradeep K Yadalam Jaime Ramírez-Arbelaez Department of Basic Sciences Faculty of Dentistry Biomedical Stomatology Research GroupUniversidad de Antioquia U de AMedellín 0057Colombia Department of postdoctoral program CIFE University CenterCuernavaca 62330MorelosMexico Department of periodontics Saveetha Dental CollegeSaveetha Institute of Medical and HealthSIMATSSaveetha UniversityChennai 600077Tamil NaduIndia Department of Transplantation Hospital San Vicente FundaciónRionegro 054047Colombia

BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ *** To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant *** A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and *** review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial *** search strategy involved analyzing multiple databases,including pubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language *** After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were *** most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also *** antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and *** concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;pported deaths in three clinical trials were 75,and there were 24 graft rejections in two *** All clinical trials reported significant proportions of antimicrobial-resistant microor

关键词： Antimicrobial resistance Antimicrobials Antivirals Solid organ transplant recipients Infections Microorganisms Cytomegalovirus

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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 p.rez 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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Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma

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World Journal of Gastroenterology 2023年第17期29卷 2571-2599页

作者： Fernanda Villarruel-Melquiades María Eugenia Mendoza-Garrido claudia M García-Cuellar Yesennia Sánchez-p.rez Julio Isael p.rez-Carreón Javier Camacho Departamento de Farmacología Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAV-IPN)Mexico City 07360Mexico Departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAVIPN)Mexico City 07360Mexico Subdirección de Investigación Básica Instituto Nacional de Cancerología(INCan)Mexico City 14080Mexico Instituto Nacional de Medicina Genómica Instituto Nacional de Medicina Genómica(INMEGEN)Mexico City 14610Mexico

Hepatocellular carcinoma(HCC)is one of the most lethal malignant tumours *** mortality-to-incidence ratio is up to 91.6%in many countries,representing the third leading cause of cancer-related *** drugs,including the multikinase inhibitors sorafenib and lenvatinib,are first-line drugs used in HCC ***,these therapies are ineffective in most cases due to late diagnosis and the development of tumour ***,novel pharmacological alternatives are urgently *** instance,immune checkpoint inhibitors have provided new approaches targeting cells of the immune ***,monoclonal antibodies against programmed cell death-1 have shown benefits in HCC *** addition,drug combinations,including first-line treatment and immunotherapy,as well as drug repurposing,are promising novel therapeutic ***,we review the current and novel pharmacological approaches to fight *** studies,as well as approved and ongoing clinical trials for liver cancer treatment,are *** pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.

关键词： Liver cancer Systemic therapy Immunotherapy Drug repurposing Drug combinations Hepatocellular carcinoma

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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 p.rez-p.rez 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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Host-parasite interactions in perpetual darkness:Macroparasite diversity in the cavefish Astyanax mexicanus

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Zoological Research 2023年第4期44卷 782-792页

作者： Ana Santacruz David Hernández-Mena Ramses Miranda-Gamboa Gerardo p.rez-ponce De León claudia patricia Ornelas-García Departamento de Zoología Instituto de BiologíaUniversidad Nacional Autónoma de MéxicoMéxico City CP 04510México Departamento de Sistemas y procesos Naturales Escuela Nacional de Estudios Superiores Unidad MéridaUcúYucatán CP 97357México Instituto de Energías Renovables Universidad Nacional Autónoma de MéxicoTemixcoMorelos CP 62580México Colección Nacional de peces Departamento de ZoologíaInstituto de BiologíaUniversidad Nacional Autónoma de MéxicoMéxico City CP 04510México Stowers Institute for Medical Research Kansas CityMO 64110USA

Astyanax mexicanus has repeatedly colonized cave environments,displaying evolutionary parallelisms in many troglobitic *** being a model system for the study of adaptation to life in perpetual darkness,the parasites that infect cavefish are practically *** this study,we investigated the macroparasite communities in 18 cavefish populations from independent lineages and compared them with the parasite diversity found in their sister surface fish populations,with the aim of better understanding the role that parasites play in the colonization of new *** the cavefish populations,we identified 13 parasite taxa,including a subset of 10 of the 27 parasite taxa known for the surface *** infecting the cavefish belong to five taxonomic groups,including trematodes,monogeneans,nematodes,copepods,and *** are the most dominant group,found in 14 *** macroparasites include species with direct life cycles and trophic transmission,including invasive ***,paired comparisons indicate higher parasite richness in the cavefish than in the surface *** variation in parasite composition across the caves suggests historical and geographical contingencies in the host-parasite colonization process and potential evolution of local *** base-line data on parasite diversity in cavefish populations of *** provides a foundation to explore the role of divergent parasite infections under contrasting ecological pressures(cave *** environments)in the evolution of cave adaptive traits.

关键词： Adaptation Metazoan parasites Niche change parasite assemblage prevalence

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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 p.rez-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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