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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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In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells

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World Journal of Gastroenterology 2025年第3期31卷 84-102页

作者： patricia de la Cruz-Ojeda Ester parras-Martínez Raquel Rey-pérez Jordi Muntané Functional Genomics of Solid Tumors Laboratory Centre de Recherche des CordeliersParis 75006France Department of Oncology Surgery Cell Therapy and Organ TransplantationInstitute of Biomedicine of SevilleVirgen del Rocio University HospitalSeville 41013Spain Biomedical Research Center for Hepatic and Digestive Diseases CIBERehdMadrid 28029Spain Department of Medical physiology and Biophysics University of SevilleSeville 41009Spain

BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology *** is still a recommended treatment for a large proportion of patients with advanced *** patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 *** To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 *** available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 *** HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 *** RNA,including small and long RNA,was extracted with a commercial miRNeasy *** was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory *** MALAT,THAp9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARp,TFAp4 and FAXDC2 in HepG2 ***12,EpB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 *** axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAp4 were of high relevance for Sorafenib response in HepG2 cells,whereas pVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib *** Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARp,TFAp4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.

关键词： Cell culture Hepatocellular carcinoma Non-coding RNA RNAseq Sorafenib

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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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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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Multiple Chemical Sensitivity: A Sickness of Suffering, Not of Dying. Descriptive Study of 33 Cases

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Health 2025年第1期17卷 65-81页

作者： Blanca Navas-Soler Aarón Gutiérrez-pastor Antonio palazón-Bru Jorge Vallejo-Ortega Álex Méndez-Jover Celia Santano-pérez Carmen Seguí-pérez Marc Seguí-pérez Sonia Cascant-pérez Juan Carlos López-Corbalán Míriam pérez-Cardona Ramón pérez-Doménech Antonio Hernández-García patricia Lorca-Amorrich Ana Belén Llinares-Llinares Cristina Valverde-Cámara Rosa María Bustos-Martínez Juan Manuel Núñez-Cruz Isidro Hernández-Isasi José Juan Martínez-pérez José Manuel Santano-López María Dolores Jover-Ríos Juan Méndez-Mora José Miguel Seguí-Ripoll Internal Medicine Service University Hospital of San Juan de Alicante Alicante Spain Family and Community Medicine Service University Hospital of San Juan de Alicante Alicante Spain Foundation for the promotion of Health and Biomedical Research of the Valencian Community (FISABIO) University Hospital of San Juan de Alicante Alicante Spain Faculty of physics University of Alicante Alicante Spain Department of Clinical Medicine Medical School University Miguel Hernandez de Elche Alicante Spain CEU Veterinary School University Cardenal Herrera Alfara del Patriarca Campus Valencia Spain Secondary School Marist Brothers High School Alicante Spain primary Medicine Hospital Francesc Borgia of Gandia Valencia Spain Faculty of Medicine CEU Cardenal Herrera University Alfara del Patriarca Campus Valencia Spain Faculty of Economics University of Alicante Alicante Spain Department of Internal Medicine Hospital La Vega Baja of Orihuela Alicante Spain

Objective: We describe patients with MCS, the evolution of the Quick Environmental Exposure and Sensitivity Inventory (QEESI) score with a special focus on people whose fillings were removed. Methods: We have conducted a retrospective longitudinal cohort study in patients diagnosed with MCS and attended in the outpatient Internal Medicine department of the University Hospital of San Juan de Alicante, from January 1, 2008 to January 1, 2021. Sociodemographic, clinical, QEESI and treatment-related variables were collected. We performed descriptive and inferential analyses. Mixed linear models were used to analyze the QEESI. Calculations were carried out with an α error of 5%. Results: Thirty-three patients were included (72.7% women, mean age 56.2). MCS was mainly triggered by mercury (N = 20) and food intolerance (N = 22). The mean interval from symptoms onset was 120 months (SD 81.6). 114 QEESIs were analyzed: 82 (N = 17 without amalgams) and 32 (N = 16 with amalgams). In patients without amalgams, severity scores increased across all subscales except the masking index (vs. with amalgams). Mean scores for the group without amalgams (vs. with amalgams) were: chemical intolerance, 62.8 points (vs. 63.4 and 46.7);other intolerances, 52.7 points (vs. 62.8 and 50.3);symptom severity, 63.2 (vs. 76.7 and 63.3);masking index, 3.9 (vs. 3.2 and 2.8);and life impacts, 63.1 (vs. 58.4 and 49.8). Conclusion: The profile of patient with MCS is a middle-aged woman who is a frequent user of healthcare services, presents a long diagnostic delay and has borne a great personal, work and socioeconomic impact. The QEESI is useful for the clinical follow-up of patients, including the optimal treatment response in the case of amalgams. Clinical Significance: people affected by Multiple Chemical Sensitivity deserve the attention, understanding and help of health professionals and family members, to face an invisible illness for those who do not suffer from it. Support is needed and doctors

关键词： Chemical Sensitivity Electromagnetic Sensitivity Mercury poisoning Amalgams QEESI

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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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The impact of endocrine-disrupting chemicals on stem cells:Mechanisms and implications for human health

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Journal of Environmental Sciences 2025年第1期147卷 294-309页

作者： Juan p.Munoz Laboratorio de Bioquímica Departamento de QuímicaFacultad de CienciasUniversidad de TarapacáArica 1000007Chile

Endocrine-disrupting chemicals(EDCs)are compounds,either natural or man-made,that interferewith the normal functioning of the endocrine *** is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction,metabolic disorders,neurological alterations,and increased risk of hormone-dependent *** cells(SCs)are integral to these pathological processes,and it is therefore crucial to understand how EDCs may influence SC *** review examines the literature on different types of EDCs and their effects on various types of SCs,including embryonic,adult,and cancer *** mechanisms through which EDCs may influence the phenotype of SCs are also ***,the possible implications of these effects on human health are *** available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways,including by altering hormonal pathways,DNA damage,epigenetic changes,reactive oxygen species production and alterations in the gene expression *** disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders,obesity,infertility,reproductive abnormalities,and ***,the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

关键词： Endocrine-disrupting chemicals Stem cells Cancer stem cells Epigenetic Hormones

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Maximum mass of magnetic white dwarfs

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Research in Astronomy and Astrophysics 2015年第10期15卷 1735-1741页

作者： Daryel Manreza paret Jorge ernesto Horvath Aurora pérez Martínez Departamento de Fisica General Facultad de FísicaUniversidad de la Habana Instituto de Astronomia Geofisica e Ciencias Atmosfericas USP Instituto de Cibernética Matemática y Física(ICIMAF)

We revisit the problem of the maximum masses of magnetized white dwarfs （WDs）. The impact of a strong magnetic field on the structure equations is addressed. The pressures become anisotropic due to the presence of the magnetic field and split into parallel and perpendicular components. We first construct stable solutions of the Tolman-Oppenheimer-Volkoff equations for parallel pressures and find that physical solutions vanish for the perpendicular pressure whenB ≥ 10^13 G. This fact estab- lishes an upper bound for a magnetic field and the stability of the configurations in the （quasi） spherical approximation. Our findings also indicate that it is not possible to obtain stable magnetized WDs with super-Chandrasekhar masses because the val- ues of the magnetic field needed for them are higher than this bound. To proceed into the anisotropic regime, we can apply results for structure equations appropriate for a cylindrical metric with anisotropic pressures that were derived in our previous work. From the solutions of the structure equations in cylindrical symmetry we have con- firmed the same bound for B- 10^13 G, since beyond this value no physical solutions are possible. Our tentative conclusion is that massive WDs with masses well beyond the Chandrasekhar limit do not constitute stable solutions and should not exist.

关键词： magnetic fields -- white dwarfs -- equation of state

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Anisotropic stellar structure equations for magnetized strange stars

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Research in Astronomy and Astrophysics 2015年第7期15卷 975-985页

作者： Daryel Manreza paret Jorge ernesto Horvath Aurora pérez Mart'nez Departamento de F'sica General Facultad de F'sica Universidad de la Habana Instituto de Astronomia Geofisica e Ciencias Atmosfericas USP Instituto de Cibernética Matemática y Física (ICIMAF)

The fact that a fermion system in an external magnetic field breaks the spherical symmetry suggests that its intrinsic geometry is axisymmetric rather than spherical. In this work we analyze the impact of anisotropic pressures, due to the presence of a magnetic field, in the structure equations of a magnetized quark *** assume a cylindrical metric and an anisotropic energy momentum tensor for the source. We found that there is a maximum magnetic field that a strange star can sustain, closely related to the violation of the virial relations.

关键词： magnetic fields -- stars: neutron -- equation of state

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