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Human CD4 ＋ effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells

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Cellular & Molecular Immunology 2013年第3期10卷 261-274页

作者： Gabriela Gonzalez-Perez Norma C Segovia Amaranta Rivas-Carvalho Diana P Reyes honorio torres-aguilar Sergio R aguilar-Ruiz Claudine Irles Gloria Soldevila Carmen Sainchez-torres 1Department of Molecular Biomedicine Centre de Investigacion y de Estudios Avanzados del I.P.N. (CINVESTAV-IPN) Mexico City Mexico Department of Physiology Facultad de Medicina Mexico City Mexico Department of Immunology Institute de Investigaciones Biomedicas Universidad Nacional Autonoma de Mexico (UNAM) Mexico City Mexico

The peripheral repertoire of CD4＋ T lymphocytes contains autoreactive cells that remain tolerant through several mechanisms. However, nonspecific CD4＋ T cells can be activated in physiological conditions as in the course of an ongoing immune response, and their outcome is not yet fully understood. Here, we investigate the fate of human naive CD4＋ lymphocytes activated by dendritic cells （DCs） presenting endogenous self-peptides in comparison with lymphocytes involved in alloresponses. We generated memory cells （Tmem） from primary effectors activated with mature autologous DCs plus interleukin （IL）-2 （Tmauto）, simulating the circumstances of an active immune response, or allogeneic DCs （Tmallo）. Tmem were generated from effector cells that were rested in the absence of antigenic stimuli, with or without IL-7. Tmem were less activated than effectors （demonstrated by CD25 downregulation） particularly with IL-7, suggesting that this cytokine may favour the transition to quiescence. Tmauto and TmaHo showed an effector memory phenotype, and responded similarly to polyclonal and antigen-specific stimuli. Biochemically, IL-7-treated Tma^o were closely related to conventional memory lymphocytes based on Erk-l/2 activation, whereas Tmauto were more similar to effectors. Autologous effectors exhibited lower responses to IL-7 than allogeneic cells, which were reflected in their reduced proliferation and higher cell death. This was not related to IL-7 receptor expression but rather to signalling deficiencies, according to STAT5 activation These results suggest that ineffective responses to IL-7 could impair the transition to memory cells of naive CD4＋ T lymphocytes recognizing self-peptides in the setting of strong costimulation.

关键词： human CD4+ T cells IL-7 memory self-peptides

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Current advances in using tolerogenic dendritic cells as a therapeutic alternative in the treatment of type 1 diabetes

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World Journal of Diabetes 2021年第5期12卷 603-615页

作者： William de Jesús Ríos-Ríos Sorely Adelina Sosa-Luis honorio torres-aguilar Department of Biochemical Sciences Faculty Universidad Autónoma“Benito Juárez”de OaxacaOaxaca 68120Mexico Department of Molecular Biomedicine Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico City 07360Mexico

Type 1 diabetes(T1D)is an autoimmune disease characterized by the destruction of insulin-producingβ-cells of the pancreatic islets by autoreactive T cells,leading to high blood glucose levels and severe long-term *** typical treatment indicated in T1D is exogenous insulin administration,which controls glucose levels;however,it does not stop the autoimmune *** strategies have been implemented aimed at stoppingβ-cell destruction,such as cellular *** cells(DCs)as an alternative in cellular therapy have gained great interest for autoimmune disease therapy due to their plasticity to acquire immunoregulatory properties both in vivo and in vitro,performing functions such as anti-inflammatory cytokine secretion and suppression of autoreactive lymphocytes,which are dependent of their tolerogenic phenotype,displayed by features such as semimature phenotype,low surface expression of stimulatory molecules to prime T cells,as well as the elevated expression of inhibitory *** may be obtained and propagated easily in optimal amounts from peripheral blood or bone marrow precursors,such as monocytes or hematopoietic stem cells,respectively;therefore,various protocols have been established for tolerogenic(tol)DCs manufacturing for therapeutic research in the treatment of *** this review,we address the current advances in the use of tolDCs for T1D therapy,encompassing protocols for their manufacturing,the data obtained from preclinical studies carried out,and the status of clinical research evaluating the safety,feasibility,and effectiveness of tolDCs.

关键词： Type 1 diabetes Dendritic cells Autoimmunity Immune tolerance Cell therapy Immunotherapy.

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Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol-and glycosaminoglycan-binding sites in the laminin receptor

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Neural Regeneration Research 2025年第3期20卷 819-820页

作者： Rayudu Gopalakrishna Jennifer aguilar Emily Lee William J.Mack Department of Integrative Anatomical Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA Department of Neurological Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA

The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models;however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated ... 详细信息

关键词： resveratrol molar dated

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Dendritic spine degeneration:a primary mechanism in the aging process

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Neural Regeneration Research 2025年第6期20卷 1696-1698页

作者： Gonzalo Flores Leonardo aguilar-Hernández Fernado García-Dolores Humberto Nicolini Andrea Judith Vázquez-Hernández Hiram Tendilla-Beltrán Instituto de Fisiología Benemérita Universidad Autónoma de Puebla(BUAP)PueblaMexico Instituto de Ciencias Forenses(INCIFO) Tribunal Superior de Justicia de la Ciudad de México(TSJCDMX).Mexico CityMexico Instituto Nacional de Medicina Genómica(INMEGEN) Mexico CityMexico

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;aguilarHernández et al., 2023).

关键词： aging process stress

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Cdk5 and aberrant cell cycle activation at the core of neurodegeneration

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Neural Regeneration Research 2023年第6期18卷 1186-1190页

作者： Raquel Requejo-aguilar Department of Biochemistry and Molecular Biology University of CórdobaCórdobaSpain Maimónides Biomedical Research Institute of Córdoba(IMIBIC) 14071 CórdobaSpain

Neurodegenerative diseases are caused by the progressive loss of specific *** exact mechanisms of action of these diseases are unknown,and many studies have focused on pathways related to abnormal accumulation and processing of proteins,mitochondrial dysfunction,and oxidative stress leading to apoptotic ***,a growing body of evidence indicates that aberrant cell cycle re-entry plays a major role in the pathogenesis of *** activation of the cell cycle in mature neurons could be promoted by several signaling mechanisms,including c-Jun N-terminal kinases,p38 mitogen-activated protein kinases,and mitogen-activated protein kinase/extracellular signal-regulated kinase cascades;post-translational modifications such as Tau-phosphorylation;and DNA damage *** all these events,implicated Cdk5,a proline-directed serine/threonine protein kinase,seems to be responsible for several cellular processes in neurons including axon growth,neurotransmission,synaptic plasticity,neuronal migration,and maintenance of neuronal ***,under pathological conditions,Cdk5 dysregulation may lead to cell cycle re-entry in post-mitotic ***,Cdk5 hyperactivation,by its physiologic activator p25,hyper-phosphorylates downstream substrates related to neurodegenerative *** review summarizes factors such as oxidative stress,DNA damage response,signaling pathway disturbance,and Ubiquitin proteasome malfunction contributing to cell cycle re-entry in post-mitotic *** also describes how all these factors are linked to a greater or lesser extent with ***,it offers a global vision of the function of cell cycle-related proteins in mature neurons with a focus on Cdk5 and how this protein contributes to the development of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease by cell cycle activation.

关键词： Alzheimer´s disease amyotrophic lateral sclerosis apoptosis Cdk5 cell cycle Huntington´s disease neurodegeneration neuron oxidative stress Parkinson´s disease signaling Tau phosphorylation

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Development and characterization of whey protein films incorporated with tarbush polyphenols and candelilla wax

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Food Bioscience 2022年第1期45卷 1-7页

作者： Olga B.Alvarez-Perez Janeth M.Ventura-Sobrevilla Cristian torres-Leon Romeo Rojas-Molina Raúl Rodríguez-Herrera Miguel A.aguilar-Gonzalez Cristobal N.aguilar Bioprocesses and Bioproducts Research Group Food Research DepartmentSchool of ChemistryUniversidad Autonoma de Coahuila25280SaltilloCoahuilaMexico School of Health Sciences Universidad Autonoma de Coahuila26090Piedras NegrasCoahuilaMexico School of Agronomy Research Center and Development for Food IndustryUniversidad Autonoma de Nuevo Leon6050General EscobedoNuevo LeonMexico Center for Research and Advanced Studies of the National Polytechnique Institute Parque Industrial Saltillo-Ramos ArizpeCoahuilaMexico

Edible films were prepared with whey protein incorporating candelilla wax,and glycerol in aqueous *** polyphenols were added as bioactive *** optimization based on the water vapor permeability(WVP)of the formulation was performed using a Box-Behnken *** films were characterized by the determination of WVP,moisture,solubility,color,antioxidant and antifungal *** electron microscopy(SEM)was also performed to observe the surface and cross-section *** lowest permeability values were found with concentrations of 1.27,0.3 and 0.5% of protein,wax and glycerol *** was proved that the addition of polyphenols into films causes a significant effect only on solubility and transparency *** films have suitable properties as a barrier for the goods they could be applied *** is proposed for use in foods such as fresh or minimally processed fruits and vegetables.

关键词： Edible films Whey protein Shelf life Candelilla wax Euphorbia antisyphilitica Fluorensia cernua polyphenols

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On the role of endogenous neurotoxins and neuroprotection in Parkinson's disease

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Neural Regeneration Research 2017年第6期12卷 897-901页

作者： Juan Segura-aguilar Molecular and Clinical Pharmacology ICBM Faculty of Medicine University of Chile

For 50 years ago was introduced L-3,4-dihydroxyphenylalanine（L-dopa） in Parkinson＇s disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson＇s disease. The question is what triggers these mechanisms. The age of normal onset in idiopathic Parkinson＇s disease suggests that environmental factors such as metals, pollutants or genetic mutations cannot be involved because these factors are related to early onset of Parkinsonism. Therefore, we have to search for endogenous neurotoxins and neuroprotection in order to understand what trigger the loss of dopaminergic neurons. One important feature of Parkinson＇s disease is the rate of the degenerative process before the motor symptoms are evident and during the disease progression. The extremely slow rate of Parkinson＇s disease suggests that the neurotoxins and the neuroprotection have to be related to dopamine metabolism. Possible candidates for endogenous neurotoxins are alpha-synuclein neurotoxic oligomers, 4-dihydroxyphenylacetaldehyde and ortho-quinones formed during dopamine oxidation to neuromelanin. Vesicular monoamine transporter-2, DT-diaphorase and glutathione transferase M2-2 seems to be the most important neuroprotective mechanism to prevent neurotoxic mechanism during dopamine oxidation.

关键词： dopamine endogenous endoplasmic degeneration reticulum extremely glutathione Dopamine transporter metabolism

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Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

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Neural Regeneration Research 2024年第3期19卷 529-535页

作者： Sandro Huenchuguala Juan Segura-aguilar Escuela de Tecnología Médica Facultad de SaludUniversidad Santo TomásLos CarrerasOsornoChile Molecular&Clinical Pharmacology Instituto de Ciencias Biomedicas(ICBM)Faculty of medicineUniversity of ChileIndependenciaSantiagoChile

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal *** preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical ***,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic *** lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big *** our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic *** exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic *** endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in t

关键词： 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 6-hydroxydopamine aminochrome dopaminergic neurons DT-diaphorase exogenous neurotoxins glutathione transferase M2-2

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Gold nanoshells： Contrast agents for cell imaging by cardiovascular optical coherence tomography

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Nano Research 2018年第2期11卷 676-685页

作者： Jie Hu Francisco Sanz-Rodríguez Fernando Rivero Emma Martín Rodríguez Río aguilar torres Dirk H. Ortgies José García Solé Fernando Alfonso Daniel Jaque Fluorescence Imaging Group Departamento de Física de Materiales Instituto Nicolás Cabrera Facultad de Ciencias Universidad Autónoma de Madrid Madrid Spain Instituto Ramón y Cajal de Investigación Sanitaria Hospital Ramón y Cajal Madrid Spain Departamento de Biología Universidad Autónoma de Madrid Madrid Spain Cardiology Department Hospital Universitario de la Princesa IIS-IP Universidad Autónoma de Madrid Madrid Spain

Optical coherence tomography （OCT） has gained considerable attention in interventional cardiovascular medicine and is currently used in clinical settings to assess atherosclerotic lesions and to optimize stent placement. Artery imaging at the cellular level constitutes the first step towards cardiovascular molecular imaging, which represents a major advance in the development of personalized noninvasive therapies. In this work we demonstrate that cardiovascular OCT can be used to detect individual cells suspended in biocompatible fluids. Importantly, the combination of this catheter-based clinical technique with gold nanoshells （GNSs） as intracellular contrast agents led to a substantial enhancement in the backscattered signal produced by individual cells. This cellular contrast enhancement was attributed to the large backscattering cross-section of GNSs at the OCT laser wavelength （1,300 nm）. A simple intensity analysis of OCT cross-sectional images of suspended cells makes it possible to identify the sub-population of living cells that successfully incorporated GNSs. The generalizability of this method was demonstrated using two different cell lines （HeLa and Jurkat cells）. This work provides novel insights into cardiovascular molecular imaging using specifically modified GNSs.

关键词： optical coherencetomography (OCT)intravascular imaging gold nanoparticles three-dimensional (3D)imaging

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State and perspectives on flavonoid neuroprotection against aminochrome-induced neurotoxicity

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Neural Regeneration Research 2021年第9期16卷 1797-1798页

作者： Victor Silva Juan Segura-aguilar Laboratory of Neurochemistry and Cell Biology Department of Biochemistry and BiophysicsInstitute of Health SciencesFederal University of Bahia40110-100SalvadorBahiaBrazil Molecular and Clinical Pharmacology ICBMFaculty of MedicineUniversity of ChileChile

Parkinson's disease(PD) motor symptoms are induced by the loss of dopaminergic neurons containing neuromelanin in the nigrostriatal system. The exact mechanism that triggers the degeneration of the nigrostriatal neurons is still unknown but there is general consensus in the scientific community that mitochondrial dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, protein degradation dysfunction of both lysosomal and proteasomal systems, endoplasmic reticulum stress.

关键词： degeneration reticulum aggregation

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