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Necroptosis in global cerebral ischemia: a role for endoplasmic reticulum stress

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Neural Regeneration Research 2020年第3期15卷 455-456页

作者： Enrique Font-Belmonte paloma gonzález-rodríguez Arsenio Fernández-López Area de Biologia Celular Instituto de BiomedicinaUniversidad de LeonLeonSpain Neural Therapies SL Edificio Institutos de InvestigacionCampus de VegazanaLeonSpain

Necroptosis has been reported in the last years as a type of regulated cell death that can be ignited by a number of specific death receptors,such as FAS,tumor necrosis factor receptor 1(TNFR1),or pathogen recognition *** cell death subroutine is involved in the response to stress and in homeostatic functions,such as the maintenance of adult T-cell balance(Galluzzi et al.,2018).Dead receptor activation leads to the recruitment of protein complexes that act as nodes of signaling that can elicit different pathways driving to death or survival,depending on the cell conditions.

关键词： death cerebral ischemia

Neuroprotective effects of meloxicam on transient brain ischemia in rats:the two faces of anti-inflammatory treatments

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Neural Regeneration Research 2023年第9期18卷 1961-1967页

作者： Irene Fernández Ugidos paloma gonzález-rodríguez María Santos-Galdiano Enrique Font-Belmonte Berta Anuncibay-Soto Diego Pérez-rodríguez JoséManuel gonzalo-Orden Arsenio Fernández-López Área de Biología Celular Instituto de BiomedicinaCampus de Vegazana s/nUniversidad de LeónLeónSpain Neural Therapies SL.Edif.Institutos de Investigación.Planta baja.Local B43.Campus de Vegazana s/n.León.Spain Department of Medicina Cirugía y Anatomía VeterinariaUniversity of LeónLeónSpain Department of Pharmacology Tulane University School of MedicineNew OrleansLAUSA Department of Neurology David Geffen School of Medicine at University of California(UCLA)Los AngelesCAUSA Department of Life Sciences Imperial College London(ICL)LondonUK Department of Clinical and Movement Neurosciences UCL Queen Square Institute of NeurologyLondonUK

The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic *** use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental *** this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic *** study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged *** show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ***,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal ***,this treatment decreased the formation of neuronal progenitor *** study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.

关键词： anti-inflammatories astrocyte axonal sprouting cylinder test doublecortin focal brain ischemia glial scar inflammation neuroprotection new neuron generation transient stroke

Hydrogels for neuroprotection and functional rewiring: a new era for brain engineering

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Neural Regeneration Research 2020年第5期15卷 783-789页

作者： Rocío Fernández-Serra Rebeca Gallego paloma Lozano Daniel gonzález-Nieto Center for Biomedical Technology Universidad Politécnica de Madrid. MadridSpain Departamento de Tecnología Fotónica y Bioingeniería ETSI TelecomunicacionesUniversidad Politécnica de MadridMadridSpain Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) MadridSpain

The neurological devastation of neurodegenerative and cerebrovascular diseases reinforces our perseverance to find advanced treatments to deal with these fatal ***-performance preclinical results have failed at clinical level,as it has been the case for a wide variety of neuroprotective agents and cell-based therapies employed to treat high prevalent brain pathologies such as stroke,Alzheimer’s and Parkinson’s *** unquestionable reality is the current absence of effective therapies to neuroprotect the brain,to arrest neurodegeneration and rewire the impaired brain *** of the problem might arise from the lack of adequate in vitro and in vivo models and that most of the underlying pathophysiological mechanisms are not yet *** contributing factor is the lack of efficient systems to sustain drug release at therapeutic concentrations and enhance the survival and function of grafted cells in transplantation *** medical applications the use of biomaterials of different compositions and formats has experienced a boom in the last *** the greater complexity of central nervous system has probably conditioned their extensive use with respect to other organs,the number of biomaterials-based applications to treat the injured brain or in the process of being damaged has grown ***-based biomaterials have constituted a turning point in the treatment of cerebral disorders using a new form of advanced *** show mechanical properties in the range of cerebral tissue resulting very suitable for local implantation of drugs and *** is also possible to fabricate three-dimensional hydrogel constructs with adaptable mesh size to facilitate axonal guidance and *** this article,we review the current trends in this area highlighting the positive impact of hydrogel-based biomaterials over the exhaustive control of drug delivery,cell engraftment and axonal reinnervation in brain p

关键词： advanced therapies Alzheimer’s disease biomaterials brain hydrogels neurological diseases Parkinson’s disease polymers stroke

Intravitreal dexamethasone implants for diabetic macular edema

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International Journal of Ophthalmology(English edition) 2018年第1期11卷 77-82页

作者： Alicia Pareja-Ríos paloma Ruiz-de la Fuente-rodríguez Sergio Bonaque-gonzález Maribel López-Gálvez Virginia Lozano-López Pedro Romero-Aroca University Hospital of the Canary Islands Santa Cruz deTenerifeIslas Canarias 38320Spain Wooptix S.L San Cristobal de La Laguna 38204Spain University Clinical Hospital of Valladolid Institute of Applied Ophthalmobiology(IOBA)Valladolid 47011Spain University Hospital Sant Joan de Reus Tarragona 43204Spain

AIM： To evaluate the safety and efficacy of a dexamethasone（DEX） intravitreal implant for diabetic macular edema（DME）.METHODS： Totally 113 eyes of 84 patients were divided in three subgroups： naive patients（n=11）, pseudophakic patients（n=72） and phakic patients（n=30）. Inclusive criterion comprised adult diabetic patients with central fovea thickening and impaired visual acuity resulting from DME for whom previous standard treatments showed no improvement in both central macular thickness（CMT） and best corrected visual acuity（BCVA） after at least 3 mo of treatment. Outcome data were obtained from patient visits at baseline and at months 1, 3, 5, 9 and 12 after the first DEX implant injection. At each of these visits, patients underwent measurement of BCVA, a complete eye examination and measurement of CMT and macular volume（MV） carried out with optical coherence tomography（OCT） images. RESULTS： Seventy-three eyes（64.5%） received a single implant, 30（26.5%） received two implants and 10（9%） received three implants. At baseline, average in BCVA, CMT and MV were 43.5±20.8, 462.8±145 and 12.6±2.5 respectively. These values improved significantly at 1 mo（BCVA： 47.2±19.5, CMT： 339.6±120, MV： 11.11±1.4） and 3 mo（BCVA： 53.2±18.1, CMT： 353.8±141, MV： 11.3±1.3）（P≤0.05）. At 5 mo（BCVA： 50.9±19.8, CMT： 425±150, MV： 12.27±2.3）, 9 mo（BCVA： 48.4±17.6, CMT： 445.5±170, MV： 12.5±2.3） and 12 mo（BCVA： 47.7±18.8, CMT： 413.2±149, MV： 12.03±2.5）, improvements in the three parameters were no longer statistically significant and decreased progressively but did not reach baseline values. There were no clinical differences between subgroups. Ocular complications were ***： Patients with DEX implants show maximum efficacy at 3 mo which then declined progressively, but is still better than baseline values at the end of follow-up.

关键词： Ozurdex diabetic macular edema dexamethasone retina diabetes

Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

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World Journal of Gastroenterology 2016年第44期22卷 9744-9751页

作者： ángel Hernández-Bartolomé Rosario López-rodríguez María Jesús Borque Leticia gonzález-Moreno Yolanda Real-Martínez Luisa García-Buey Ricardo Moreno-Otero paloma Sanz-Cameno Gastroenterology Service Instituto Investigación Sanitaria Princesa Molecular Biology Unit Instituto Investigación Sanitaria Princesa CIBERehd

AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR *** were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUC-ROC).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease(P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in *** Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.

关键词： Chronic hepatitis C Area under the curve of receiver operator characteristics Liver fibrosis Cirrhosis Angiopoietin-2 Angiopoietin-1 Biomarker Angiogenesis

Neurodevelopmental disorders:An innovative perspective via the response to intervention model

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World Journal of Psychiatry 2021年第11期11卷 1017-1026页

作者： Celestino rodríguez Debora Areces Trinidad García Marisol Cueli paloma gonzalez-Castro Department of Psychology University of OviedoOviedo 33003AsturiasSpain

Neurodevelopmental disorders are a group of conditions classified together by the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders which include intellectual disability,communication disorders,autism spectrum disorder,attention-deficit/hyperactivity disorder,specific learning disorder(SLD),and motor *** is present in many students,who exhibit significant difficulties in the acquisition of reading,written expression,and mathematics,mostly due to problems with executive functions(EF).The present study is a review of the current situation of neurodevelopmental disorders and SLD focusing on the benefits of the response to intervention model(RtI),which allows the combination of evaluation and intervention *** also addresses the key role of *** importance of adapting RtI to new possibilities such as the use of virtual reality is discussed and a theoretical framework for carrying that out is provided.

关键词： Neurodevelopmental disorders Specific learning disorder Response to intervention model Virtual reality

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

Development of a modified predicted heat strain model for hot work environments

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International Journal of Mining Science and Technology 2020年第4期30卷 477-481页

作者： paloma Lazaro Moe Momayez Department of Mining and Geological Engineering The University of ArizonaTucsonAZ 85750USA

Excessive exposure to heat can lead to injuries,illness,and death among *** actual cost of heat-related injuries and illnesses is unknown because of underreporting and lack of symptom ***-factorial,evidence-based,and field-ready guidelines for identifying–and predicting–physiolo gical markers of heat strain are currently *** predicted heat strain(PHS)model,is the latest attempt by mining companies to aid in the evaluation and management of occupational heat *** adopted algorithm relies on worksite environmental measurements and an estimate of individual metabolic rate for mine workers to provide an estimate of the workers’core temperature during a work *** are several known limitations of the PHS model,including the assumption that the subject worker is hydrated and fit.A modified PHS model was presented based on eight physical parameters that are measured at different intervals during a work shift;these parameters are air temperature,relative humidity,air velocity,radiation,metabolic rate,acclimatization,clothing insulation and *** validate the results,the predictions from the modified PHS model were compared with direct physiological measurements obtained from ingestible pills and heat stress monitors under different environmental and working conditions.

关键词： Predicted heat strain Hot underground mines Heat strain Heat stress

Newly Described Components and Regulatory Mechanisms of Circadian Clock Function in Arabidopsis thaliana

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Molecular Plant 2012年第3期5卷 545-553页

作者： Manuel Adrian Troncoso-Ponce and paloma Mas Center for Research in Agricultural Genomics （CRAG） Parc de Recerca UAB Edifici CRAG Barcelona 08193 Spain

The circadian clock temporally coordinates plant growth and metabolism in close synchronization with the diurnal and seasonal environmental changes. Research over the last decade has identified a number of clock components and a variety of regulatory mechanisms responsible for the rhythmic oscillations in metabolic and physiological activities. At the core of the clock, transcriptional/translational feedback loops modulate the expression of a significant proportion of the genome. In this article, we briefly describe some of the very recent advances that have improved our understanding of clock organization and function in Arabidopsis thaliana. The new studies illustrate the role of clock protein complex for- mation on circadian gating of plant growth and identify alternative splicing as a new regulatory mechanism for clock function. Examination of key clock properties such as temperature compensation has also opened new avenues for func- tional research within the plant clockwork. The emerging connections between the circadian clock and metabolism, hor- mone signaling and response to biotic and abiotic stress also add new layers of complexity to the clock network and underscore the significance of the circadian clock regulating the daily life of plants.

关键词： circadian clock circadian rhythms Arabidopsis thaliana feedback loops.