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Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

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Neural Regeneration Research 2024年第8期19卷 1835-1841页

作者： Irene Navarro-Lobato Mariam Masmudi-Martín Manuel F.López-Aranda Juan F.López-Téllez Gloria Delgado Pablo Granados-Durán Celia Gaona-Romero marta Carretero-Rey Sinforiano Posadas María E.Quiros-ortega Zafar U.Khan Laboratory of Neurobiology Centro de Investigaciones Médico Sanitarias(CIMES)University of MalagaMalagaSpain Department of Medicine Faculty of MedicineUniversity of MalagaMalagaSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) Institute of Health Carlos IIIMadridSpain the Donders Institute for Brain Cognition and Behaviour Radboud UniversityNijmegenThe Netherlands the Brain Metastasis Group National Cancer Research Centre(CNIO)MadridSpain the Department of Neurobiology University of California-Los AngelesLos AngelesCAUSA

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

关键词： behavioral performance brain-derived neurotrophic factor cognitive dysfunction episodic memory memory circuit activation memory deficits memory enhancement object recognition memory prevention of memory loss regulator of G protein signaling

Development and screening of(Ca-P-Si-F)-PEO coatings for biodegradability control of Mg-Zn-Ca alloys

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Journal of Magnesium and Alloys 2022年第8期10卷 2220-2237页

作者： Lara moreno marta Mohedano Raul Arrabal Endzhe Matykina Departamento de Ingeniería Química y de Materiales Facultad de Ciencias QuímicasUniversidad Complutense de Madrid28040 MadridSpain

PEO coatings were developed on MgZnxCayalloys for biomedical applications using different treatment times and a novel transparent electrolyte containing Ca,P,Si and F.Surface characteristics and chemical composition of studied materials were evaluated using scanning electron microscopy,X-ray diffraction and optical metrology.Corrosion investigations were performed for uncoated and coated materials using potentiodynamic polarization,electrochemical impedance spectroscopy and hydrogen evolution measurements in three media(0.9wt.%NaCl,α-MEM and inorganic part ofα-MEM).Findings revealed that Zn-rich intermetallics favour the formation of large voids in the coatings.Ca,P,F and Si are successfully incorporated into the coatings.Coatings consist of crystalline phases(Mg O,Mg F_(2)and Ca,Si-rich compounds)and amorphous material.Aminoacids and organic components ofα-MEM solution accelerate corrosion of the bare substrates but have no significant influence on the corrosion resistance of coated specimens.Therefore,inorganicα-MEM can be considered as an appropriate medium for fast screening of PEO coatings.The relatively small amount of F content in the barrier layer facilitates early failure of the coatings,which show undercoating corrosion.Zn-rich intermetallic particles in the undercoating crevice induce a more aggressive corrosive environment and enhanced micro-galvanic couple effect with the Mg matrix.This leads to faster degradation of the coated alloys compared to the bare substrates.

关键词： Magnesium Biomaterials Plasma electrolytic oxidation Corrosion

NHC-catalysed[3+2]-asymmetric annulation between pyrazolin-4,5-diones and enals:synthesis of novel spirocyclic pyrazolone γ-butyrolactones and computational study of mechanism and stereoselectivity

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Organic Chemistry Frontiers 2022年第2期9卷 420-427页

作者： marta Gil-Ordonez Alicia Maestro Pablo ortega Pablo G.Jambrina Jose M.Andres GIR-SintACat-Instituto Universitario CINQUIMA y Departamento de Química Orgánica Facultad de CienciasUniversidad de ValladolidPaseo Belén 747011 ValladolidSpain Departamento de Química Física University of Salamanca37008 SalamancaSpain

Chiral pyrazolones with a spirocyclic centre at the C4-position are widely found in a large family of medically relevant compounds.In recent years,organocatalysis,particularly that performed with quiral N-heterocyclic carbenes(NHCs),has allowed the enantioselective synthesis of these spirocyclic compounds despite its inherent difficulty.In this work,we describe the fully diastereo-and highly enantioselective synthesis of novel spirocyclic pyrazolone γ-butyrolactones via NHC-catalysed[3+2]annulation reaction of enals and 1H-pyrazol-4,5-diones.To understand the catalytic mechanism and origin of stereoselectivity,electronic structure calculations were carried out.After considering various pathways,we concluded that the stereoselectivity-determining step is the formation of the lactone that proceeds after addition of the NHC derived homoenolate to the electrophilic carbonyl group of pyrazolin-4,5-dione.Our calculations predict that the free energy barrier is lower for the(RS)product,which is also the main product experimentally obtained.

关键词： synthesis spiro mechanism

As-cast and extruded Mg-Zn-Ca systems for biodegradable implants:Characterization and corrosion behavior

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Journal of Magnesium and Alloys 2023年第3期11卷 1102-1120页

作者： Lara moreno Endzhe Matykina Kiryl A.Yasakau Carsten Blawert Raul Arrabal marta Mohedano Departamento de Ingeniería Química y de Materiales Facultad de Ciencias QuímicasUniversidad Complutense de Madrid28040 MadridSpain Department of Materials and Ceramic Engineering CICECO-Aveiro institute of materialsUniversity of Aveiro3810-193 AveiroPortugal Institute of Surface Science Helmholtz-Zentrum HereonMax-Planck Strasse 1Geesthacht 21502Germany

The aim of the present study is to evaluate the effect of alloy processing and composition as well as the pH control and testing medium on the in vitro corrosion performance of Mg-Zn-Ca systems for biodegradable implants.The grain size and secondary phases were analyzed by optical microscopy,scanning electron microscopy,transmission electron microscopy,and X-ray diffraction.Scanning kelvin probe force microscopy(SKPFM)was used to analyze the Volta potential values of the second phases.The corrosion performance of the three alloys was evaluated by electrochemical and hydrogen evolution methods inα-MEM with and without organic species(i.***.complete and inorganicα-MEM).Two strategies were followed to evaluate the influence of the pH on the corrosion behavior:daily solution replacement and CO_(2)flow based pH control.For all the materials,the organic medium accelerates the corrosion process.Constant pH maintained by CO_(2)flow through the medium results in considerably higher corrosion rates for all alloys.The impact of pH is lesser on the as-cast alloys due to the barrier effect of the secondary phases,particularly pronounced in the Mg1Zn1Ca alloy which showed the lowest corrosion rate.The wrought Mg0.5Zn0.2Ca alloy that lacks the refined secondary phase network and exhibits high number of twins undergoes accelerated uniform corrosion under constant pH conditions.

关键词： MgZnCa Magnesium Biomaterials Characterization Corrosion

Association between urinary concentrations of bisphenol A substitutes and diabetes in adults

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World Journal of Diabetes 2022年第7期13卷 521-531页

作者： Rafael moreno-Gómez-Toledano Esperanza Vélez-Vélez María I Arenas marta Saura Ricardo J Bosch Universidad de Alcalá Department of Biological Systems/Physiology UnitAlcaláde Henares 28871Spain Fundación Jiménez Díaz School of Nursing Jiménez Díaz FoundationAutonomous University of MadridMadrid 28040Spain Universidad de Alcalá Department of Biomedicine and BiotechnologyAlcaláde Henares 28871Spain Centro de Investigación en Red de Enfermedades Cardiovasculares Instituto Ramón y Cajal de Investigación SanitariaMadrid 28034Spain

BACKGROUND Due to new restrictions on the use of bisphenol A(BPA),industries are beginning to replace it with derived molecules such as bisphenol S and F(BPS and BPF).There is extensive evidence in the academic literature on the potential health effects of BPA,which is known to be a diabetogenic molecule.However,there are few publications related to new compounds derived from BPA.AIM To perform an epidemiological study of urinary BPS and BPF in the American National Health and Nutrition Examination Survey(NHANES)cohort,and analyze their possible relationship with diabetes mellitus.METHODS NHANES datasets from 2013 to 2016 were used due to the urinary BPF and BPS availability.Data from 3658 adults were analyzed to perform regression analysis exploring the possible relationship between BPA-derived compounds and diabetes.RESULTS Descriptive statistics,linear regression modeling,and logistic regression analysis revealed a significant relationship between urinary BPS,but not BPF,and diabetes risk.Additionally,a relationship was observed between both compounds and hypertension and a slight relationship between BPF and dyslipidemia.CONCLUSION In the present study,a strong relationship between urinary BPS,not BPF,and diabetes risk has been determined.BPA substitute molecules do not exempt the population from potential health risks.

关键词： Bisphenol S Bisphenol F Diabetes mellitus National Health and Nutrition Examination Survey Urine

Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

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World Journal of Stem Cells 2022年第7期14卷 453-472页

作者： Victoria Pulido-Escribano Bárbara Torrecillas-Baena marta Camacho-Cardenosa Gabriel Dorado MaríaÁngeles Gálvez-moreno Antonio Casado-Díaz Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17 Instituto Maimónides de Investigación Biomédica de CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain Dep.Bioquímica y Biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de CórdobaCIBERFESCórdoba 14071Spain

The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.

关键词： Cell priming Extracellular vesicles Hypoxia Hypoxia-inducible factor Mesenchymal stemcells Regenerative medicine

Effectiveness of statins vs.exercise on reducing postprandial hypertriglyceridemia in dyslipidemic population:A systematic review and network meta-analysis

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Journal of Sport and Health Science 2022年第5期11卷 567-577页

作者： Laura Alvarez-Jimenez Alfonso moreno-Cabanas Miguel Ramirez-Jimenez Felix Morales-Palomo Juan Fortega Ricardo Mora-Rodriguez Exercise Physiology Lab at Toledo Sports Science DepartmentUniversity of Castilla-La ManchaToledo 45004Spain

Background:Individuals at risk of suffering cardiovascular disease(CVD) present with larger increases in blood trigyceride(TG) concentration after a high-fat meal than do healthy individuals.These postprandial hypertriglyceride levels are an independent risk factor for CVD.Prescription of statins and a bout of prolonged exercise are both effective in lowering postprandial hypertriglyceride levels.We aimed to evaluate the comparative effectiveness of statins vs.a bout of aerobic exercise in reducing fasting and postprandial TG(PPTG) concentrations in indiv、duals at high nsk of developing CVD.Methods:Thirty-seven sltudies from a systematic literature search of the PubMed,EMBASE,and Cochrane databases were included in this review.The selected studies conducted trials involving statin therapy(n=20) or a bout of aerobic exercise(n=19) and measured their impact on PPTG levels as the outcome.Two studies analyzed both treatments and were included in duplicate.The meta-analysis was constructed using a random-effects model to calculate the mean difference(MD).The Student t test was used to compare the data sets for statins vs.exercise.Results:Overall,statin and exercise interventions showed similar reductions in PPTG levels,with an MD of-0.65 mmol/L for statins(95% confidence interval(95%CI):-0.54 to-0.77;p <0.001) and-0.46 mmol/L for exercise(95%CI:-0.21 to-0.71;p <0.01).However,statins lowered fasting TG levels more than exercise(MD=-1.54 mmol/L,95%CI:-2.25 to-0.83;p=0.009).Conclusion:Although aerobic exercise is effective in lowering blood TG levels,statins seem to be more efficient,especially in the fasted state.A combination of exercise and statins might reveal a valuable approach to the treatment and prevention of CVD.More studies are required to determine the underlying mechanisms and the possible additive effects of these interventions.

关键词： Aerobic exercise Cardiovascular disease Hydroxymethylglutaryl-CoA reductase inhibitor Meta-analysis Metabolic syndrome

Hyperthermic intraperitoneal chemotherapy:Rationale and technique

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World Journal of Gastrointestinal Oncology 2010年第2期2卷 68-75页

作者： Santiago González-moreno Luis A González-Bayón Gloria ortega-Pérez Peritoneal Surface Oncology Program Department of Surgical OncologyCentro Oncológico MD Anderson International Espaa28033 MadridSpain

The combination of complete cytoreductive surgery and perioperative intraperitoneal chemotherapy provides the only chance for long-term survival for selected patients diagnosed with a variety of peritoneal neoplasms,either primary or secondary to digestive or gynecologic malignancy.Hyperthermic intraperitoneal chemotherapy (HIPEC) delivered in the operating room once the cytoreductive surgical procedure is fi nalized,constitutes the most common form of administration of perioperative intraperitoneal chemotherapy.This may be complemented in some instances with early postoperative intraperitoneal chemotherapy (EPIC).HIPEC combines the pharmacokinetic advantage inherent to the intracavitary delivery of certain cytotoxic drugs,which results in regional dose intensification,with the direct cytotoxic effect of hyperthermia.Hyperthermia exhibits a selective cell-killing effect in malignant cells by itself,potentiates the cytotoxic effect of certain chemotherapy agents and enhances the tissue penetration of the administered drug.The chemotherapeutic agents employed in HIPEC need to have a cell cycle nonspecific mechanism of action and should ideally show a heat-synergistic cytotoxic effect.Delivery of HIPEC requires an apparatus that heats and circulates the chemotherapeutic solution so that a stable temperature is maintained in the peritoneal cavity during the procedure.An open abdomen (Coliseum) or closed abdomen technique may be used,with no signif icant differences in eff icacy proven to date.Specif ic technical training and a solid knowledge of regional chemotherapy management are required.Concerns about safety of the procedure for operating room personnel are expected but are manageable if universal precautions and standard chemotherapy handling procedures are used.Different HIPEC drug regimens and dosages are currently in use.A tendency for concurrent intravenous chemotherapy administration (bidirectional chemotherapy,so-called "HIPEC plus") has been observed in recent years,with the aim to further enhance the cyt

关键词： Hyperthermia Intracavitary chemotherapy Peritoneal neoplasms Peritoneal carcinomatosis Cytoreductive surgery

Pure and mixed plantations of Persian walnut (Juglans regia L.) for high quality timber production in Chile, South America

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Journal of Plant Ecology 2020年第1期13卷 12-19页

作者： Verónica Loewe-Muñoz Mónica Balzarini marta ortega González Chilean Forest Institute(INFOR) Metropolitan OfficeSucre 2397ÑuñoaSantiagoChile CONICET Biometry Unit College of AgricultureUniversidad Nacional de CórdobaCiudad UniversitariaCC509CP 5000CórdobaArgentina Chilean Forest Institute(INFOR) Biobío OfficeCamino a Coronel Km 7.5San Pedro de la PazConcepciónChile

波斯胡桃(Juglans regia L.)是用于装饰工业的一种森林物种,需要适当的管理才能生产出经济效益好的高质量原木。由于种间关联和管理水平可以提高林分生产力,因此本研究的创新之处在于评估波斯胡桃在不同混合种植中以及在适度的管理强度... 详细信息

波斯胡桃(Juglans regia L.)是用于装饰工业的一种森林物种,需要适当的管理才能生产出经济效益好的高质量原木。由于种间关联和管理水平可以提高林分生产力,因此本研究的创新之处在于评估波斯胡桃在不同混合种植中以及在适度的管理强度的纯人工林中的表现。在两种截然不同的管理方案下种植纯林和混交林后,连续7年每年对波斯胡桃的生长、直度和存活率进行测定。在第7年时,记录所有人工林中病害情况。在每种管理强度下,除纯林外,检验三种混交林:仅与主要森林物种混交、主要森林物种和黑桤木(Alnus glutinosa L.,伴生种)混交,以及主要物种和灌木俄罗斯橄榄(Elaeagnus angustifolia L.,保育种)混交。利用重复生长数据对人工林类型与管理方案之间的交互作用进行检验。研究发现人工林类型与管理方案的交互作用显著,表明在管理水平高和低的条件下,人工林效应存在不同的机制。与纯林相比,在低管理水平下,有保育灌木混交的波斯胡桃的树高增加了78%、直径生长增加了53%。同样,在管理强度不高的情况下,与灌木混交有更多的健康益处(胡桃枯萎病的发生率低于单一栽培)和更好的直度。在高管理强度下(灌溉、施肥、抚育和频繁修剪),与俄罗斯橄榄混交时这些有益效应消失。因此,波斯胡桃种植园的具体选址设计取决于可预见的管理强度。

关键词：高质量木材单一栽培森林协会伴生种俄罗斯橄榄