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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

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Mesenchymal stromal cell therapy for damaged retinal ganglion cells, is gold all that glitters?

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Neural Regeneration Research 2019年第11期14卷 1851-1857页

作者： Fernando Lucas-Ruiz Caridad Galindo-Romero David García-Bernal María Norte-Munoz Kristy T. Rodríguez-Ramírez manuel salinas-navarro Jose E. Millán-Rivero manuel Vidal-Sanz Marta Agudo-Barriuso Grupo de Oftalmologia Experimental Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca)MurciaSpain Department of Talmologia Universidad de MurciaMurciaSpain Unidad de Terapia Celular y Trasplante Hematopoyetico Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca)MurciaSpain Department of Medicina Interna Universidad de MurciaMurciaSpain

Mesenchymal stromal cells are an excellent source of stem cells because they are isolated from adult tissues or perinatal derivatives, avoiding the ethical concerns that encumber embryonic stem cells. In preclinical models, it has been shown that mesenchymal stromal cells have neuroprotective and immunomodulatory properties, both of which are ideal for central nervous system treatment and repair. Here we will review the current literature on mesenchymal stromal cells, focusing on bone marrow mesenchymal stromal cells, adipose-derived mesenchymal stromal cells and mesenchymal stromal cells from the umbilical cord stroma, i.e.,Wharton’s jelly mesenchymal stromal cells. Finally, we will discuss the use of these cells to alleviate retinal ganglion cell degeneration following axonal trauma.

关键词： stem cells adipose stem cells umbilical cord bone marrow Wharton's jelly optic nerve axotomy neuroprotection

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Abiotic and biotic drivers of struvite solubilization in contrasting soils

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Pedosphere 2023年第6期33卷 828-837页

作者： Antonio RUIZ-navarro manuel DELGADO-BAQUERIZO Concha CANO-DíAZ Carlos GARCíA Felipe BASTIDA Centro de Edafologia y Biologia Aplicada del Segura Consejo Superior de Investigaciones Cientificas(CEBAS-CSIC)Department of Soil and Water ConservationEspinardoMurcia E-30100Spain ICL Specialty Fertilizers Iberia TotanaMurcia E-30850Spain Laboratorio de Biodiversidad y Funcionamiento Ecosistemico Instituto de Recursos Naturales y Agrobiologia de Sevilla(IRNAS)CSICAv.Reina Mercedes 10Sevilla E-41012Spain IRNAS-CSIC Unidad Asociada Universidad Pablo de OlavideUniversidad Pablo de Olavide(UPO)Sevilla 41013Spain Centre for Research and Development in Agrifood Systems and Sustainability(CISAS) Instituto Politecnico de Viana do Castelo(IPVC)Rua Escola Industrial e Comercial Nun'Alvares 34Viana do Castelo 4900-347Portugal

Phosphorus(P) limitation in the coming decades calls for the utilization of alternative fertilizers in agriculture. Struvite is a promising P source, but its potential role as a fertilizer is dependent on different physical, chemical, and biological properties, which are very heterogeneous in soil, complicating the prediction of the best soil conditions for its application. Here, we evaluated the solubility of struvite in soil, its redistribution into P fractions, and its potential abiotic and biotic drivers in 62 globally distributed soils with contrasting properties through an incubation assay. We found that after 40 d, about 35% of struvite P was redistributed into soil fractions more accessible to plants and microbes. Phosphorus redistribution from struvite was driven by a complex suite of soil physical, chemical, and microbial properties as well as environmental factors that varied across soils. Soil texture played a critical role in determining the redistribution of P in struvite-amended soils in soluble(H2O extraction), labile(NaHCO3 extraction), and moderately labile(NaOH extraction) fractions.In addition, the soil solution cation concentration was one of the most important drivers of available struvite-derived P fractions. The great importance of texture and cations in determining struvite-derived P fractions in soil was contrasted with the relatively minor role of pH. At the microbial level, the number of bacterial operational taxonomic units(OTUs) from the unfertilized soils that correlated with struvite-derived P fractions was higher than that of fungi. The number of OTUs that correlated with the struvite-derived soluble P fraction was dominated by fungi, whereas the number of OTUs that correlated with the struvite-derived labile P fraction was dominated by bacteria. Overall, this study provided a predictive framework for the potential use of struvite as a P fertilizer in contrasting soils.

关键词： bacteria fungi environmental factor operational taxonomic unit phosphorus fertilizer phosphorus fraction phosphorus solubilization soil fertility soil property

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Validation of a preclinical dry eye model in New Zealand white rabbits during and following topical instillation of 1% ophthalmic atropine sulfate

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Animal Models and Experimental Medicine 2022年第3期5卷 266-273页

作者： Alejandra Sánchez-Ríos Elba Yadira Correa-Gallegos José manuel Medina-Espinoza Andrea Anaid navarro-Sanchez Oscar Olvera-Montaño Leopoldo Baiza-Durán Patricia Muñoz-Villegas Medical Affairs Department Laboratorios SophiaSA de CVZapopanJaliscoMexico

Background : The objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate(OAS) in New Zealand white(NZW) rabbits.Methods : OAS(1%) was applied three times per day to 30 eyes of 15 healthy NZW rabbits. Sacrifice, enucleation, and lacrimal gland removal took place on days 15, 21,and 30(OAS group). A second group(n = 5) was used as control. Clinical evaluations took place on days 3, 10, 15, 18, 21, 24 and 30. The primary endpoints were:Schirmer I test, tear break-up time(TBUT), and corneal fluorescein staining. As secondary endpoints, clinical changes including intraocular pressure, and histopathology were evaluated.Results : While OAS was administered, the Schirmer I test showed a statistically significant reduction for OAS group versus control( p < 0.001), and versus basal production( p < 0.001). TBUT showed statistically significant differences between groups(days 3 and 10;p = 0.001) and versus basal values(day 3;p < 0.001). Fluorescein staining showed a statistically significant difference(day 3;p = 0.001). The most frequent clinical finding was conjunctival hyperemia(76.9% OAS vs. 20% control). For histopathology, all OAS subjects presented some degree of inflammation(86.7% minimal;13.3% mild) whereas the control presented only 30% minimal inflammation. Goblet cell density showed no difference.Conclusions : The effectiveness of the OAS dry eye model in NZW rabbits as reported in previous studies was confirmed, provided that the application of the drug is maintained throughout the intervention;it is not a viable model after OAS administration is suspended.

关键词： atropine sulfate dry eye rabbit model safety Schirmer I test TBUT

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Estimation of rainfall thresholds for shallow landslides in the Sierra Madre Oriental, northeastern Mexico

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Journal of Mountain Science 2020年第7期17卷 1565-1580页

作者： Jorge A.salinas-Jasso Fernando Velasco-Tapia Ignacio navarro de León Ricardo A.salinas-Jasso Efraín Alva-Nino Facultad de Ciencias de la Tierra Universidad Autónoma de Nuevo LeónEx-Hacienda de Guadalupe km 8.Carr.Linares-Cerro PrietoLinaresN.L.67700México Secretaría de Desarrollo Sustentable de Nuevo León Washington #2000Col.ObreraMonterreyN.L.64010México

Landslides induced by prolonged rainfalls are frequent mass movements along the northeastern portion of the Sierra Madre Oriental in Mexico,causing significant damage to infrastructure.In this work,we have studied the connection between rainfall and landslides in the Santa Rosa Canyon,a catchment located in the northeastern Mexico.A landslide database triggered by major storms and hurricanes that have hit the region over the past 30 years was analyzed.A total of 92 rainfall events in the Santa Rosa Canyon were studied to determine the amount of precipitation needed to trigger shallow landslides.For each event the duration(D,in hours)and the cumulated rainfall event(E,in mm)were determined by using historical rainfall data from weather stations located near the study area.We have proposed an ED threshold for rainfall-induced landslides with durations 0.5

关键词： Shallow landslides Cumulated rainfall Rainfall thresholds Northeastern Mexico Early warning systems.

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Clones identification of Sequoia sempervirens (D. Don) Endl. in Chile by using PCR-RAPDs technique

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2009年第2期10卷 112-119页

作者： manuel TORALIBAEZ Margarita CARU Miguel A. HERRERA Luis GONZALEZ Luis M. MARTIN Jorge MIRANDA Rafael M. navarro-CERRILLO Department of Forest Management Faculty of ForestryUniversity of Chile Santa Rosa 11315La PintanaSantiagoChile Department of Ecological Sciences Faculty of SciencesUniversity of ChileSanta Rosa 11315La PintanaSantiagoChile Department of Forestry School of Agriculture and Forestry University of Córdoba14080 CórdobaSpain Department of Genetic School of Agriculture and ForestryUniversity of Córdoba14080 CórdobaSpain Department of Forest Management Faculty of ForestryUniversity of ChileSanta Rosa 11315La PintanaSantiagoChile

A protocol of polymerase chain reaction-random amplified polymorphic DNAs (PCR-RAPDs) was established to analyse the gene diversity and genotype identification for clones of Sequoia sempervirens (D. Don) Endl. in Chile. Ten (out of 34) clones from introduction trial located in Voipir-Villarrica, Chile, were studied. The PCR-RAPDs technique and a modified hexadecyltrimethylammonium bromide (CTAB) protocol were used for genomic DNA extraction. The PCR tests were carried out employing 10-mer random primers. The amplification products were detected by electrophoresis in agarose gels. Forty nine polymorphic bands were obtained with the selected primers (BG04, BF07, BF12, BF13, and BF14) and were ordered according to their molecular size. The genetic similarity between samples was calculated by the Jaccard index and a dendrogram was con- structed using a cluster analysis of unweighted pair group method using arithmetic averages (UPGMA). Of the primers tested, 5 (out of 60) RAPD primers were selected for their reproducibility and high polymorphism. A total of 49 polymorphic RAPD bands were detected out of 252 bands. The genetic similarity analysis demonstrates an extensive genetic variability between the tested clones and the dendrogram depicts the genetic relationships among the clones, suggesting a geographic relationship. The results indicate that the RAPD markers permitted the identification of the assayed clones, although they are derived from the same geo- graphic origin.

关键词： RAPD标记技术 PCR检测基因型鉴定北美红杉无性系随机扩增多态性DNA 智利基因组DNA提取

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Simultaneous pars plana vitrectomy,panretinal photocoagulation,cryotherapy,and Ahmed valve implantation for neovascular glaucoma

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International Journal of Ophthalmology(English edition) 2021年第9期14卷 1396-1401页

作者： Carolina Bernal-Morales Marina Dotti-Boada Alvaro Olate-Perez manuel J.navarro-Angulo Laura Pelegrín Marc Figueras-Roca Institut Clínic d’Oftalmologia(ICOF) Hospital ClínicBarcelona 08028Spain August Pi i Sunyer Biomedical Research Institute(IDIBAPS) Barcelona 08028Spain

AIM:To describe and evaluate the efficacy of Ahmed glaucoma valve implantation(AGV)combined with pars plana vitrectomy(PPV)in a single surgical act for the treatment of advanced neovascular glaucoma(NVG).METHODS:Retrospective observational case series included 51 eyes from 50 patients with severe NVG treated with PPV,AGV,and panretinal photocoagulation and/or cryotherapy in a single surgical act during a 13-year period(2005-2018).Preoperative,intraoperative and postoperative data at day 1 and months 1,3,6,21,and 24 were systematically collected.Definition of surgical success was stablished at IOP between 6 and 21 mm Hg with or without topical treatment.RESULTS:Main indications for surgery were NVG secondary to proliferative diabetic retinopathy(39.2%)and central retinal vein occlusion(37.3%).Mean(±SD)preoperative IOP was 42.0±11.2 mm Hg decreasing to 15.5±7.1 mm Hg at 12 mo and 15.8±9.1 mm Hg at 24 mo of follow up.Cumulative incidence of success of IOP control was 76.0%at first postoperative month,reaching 88.3%at 6 mo.Prevalence of successful IOP control at long term was 74.4%at 12 mo and 71.4%at 24 mo.Eye evisceration for unsuccessful NVG management was required in 1 case(2.0%).CONCLUSION:Combination of AGV implantation and PPV in a single act may be a suitable option for severe forms of NVG in a case-by-case basis for effective IOP control and a complete panretinal photocoagulation.

关键词： neovascular glaucoma Ahmed valve pars plana vitrectomy panretinal photocoagulation cryotherapy

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IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice

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International Journal of Oral Science 2020年第1期12卷 31-39页

作者： Angustias Page Ana Bravo Cristian Suarez-Cabrera Raquel Sanchez-Baltasar Marta Oteo Miguel Angel Morcillo MLlanos Casanova Jose CSegovia manuel navarro Angel Ramirez Molecular Oncology Unit.Centro de Investigaciones Energéticas Medioambientales y Tecnológicas(CIEMAT)MadridSpain Instituto de Investigación 12 de Octubre i+12 MadridSpain Centro de Investigación Biomédica en Red de Cáncer(CIBERONC) MadridSpain Department of Anatomy Animal Production and Veterinary Clinical SciencesLaboratory of Pathology Phenotyping of Genetically Engineered MiceFaculty of Veterinary MedicineUniversity of Santiago de CompostelaLugoSpain Biomedical Applications and Pharmacokinetics Unit Centro de Investigaciones EnergéticasMedioambientales y Tecnológicas(CIEMAT)MadridSpain Hematopoietic Innovative Therapies Division.Centro de Investigaciones Energéticas Medioambientales y Tecnológicas(CIEMAT).Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)MadridSpain Unidad Mixta de Terapias Avanzadas Fundación Instituto de Investigaciones Sanitarias Fundación Jiménez DíazMadridSpain

Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog,MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ(a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and mi RNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins(p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity.These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epithelia.

关键词： IKKβ tumour suppressor

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Analysis of the postoperative hemostatic profile of colorectal cancer patients subjected to liver metastasis resection surgery

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World Journal of Clinical Cases 2019年第17期7卷 2477-2486页

作者： Guillermo Perez navarro Ana Maria Pascual Bellosta Sonia María Ortega Lucea Mario Serradilla Martín Jose manuel Ramirez Rodriguez Javier Martinez Ubieto Department of Anesthesiology University Hospital Miguel ServetZaragoza 50009Spain Department of General Surgery University Hospital Miguel ServetZaragoza 50009Spain Department of General Surgery University Hospital Lozano BlesaZaragoza 50009Spain

BACKGROUND Liver resection surgery has advanced greatly in recent years,and the adoption of fasttrack programs has yielded good results.Combination anesthesia (general anesthesia associated to epidural analgesia) is an anesthetic-analgesic strategy commonly used for the perioperative management of patients undergoing surgery of this kind,though there is controversy regarding the coagulation alterations it may cause and which can favor the development of spinal hematomas.AIM To study the postoperative course of liver resection surgery,an analysis was made of the outcomes of liver resection surgery due to colorectal cancer metastases in our centre in terms of morbiditymortality and hospital stay according to the anesthetic technique used (general vs combination anesthesia).METHODS A prospective study was made of 61 colorectal cancer patients undergoing surgery due to liver metastases under general and combination anesthesia between January 2014 and October 2015.The patient characteristics,intraoperative variables,postoperative complications,evolution of hemostatic parameters,and stay in intensive care and in hospital were analyzed.RESULTS A total of 61 patients were included in two homogeneous groups: general anesthesia (n = 30) and combination anesthesia (general anesthesia associated to epidural analgesia)(n = 31).All patients had normal coagulation values before surgery.The international normalized ratio (INR) in both the general and combination anesthesia groups reached maximum values at 2448 h (mean 1.37 and 1.45 vs 1.39 and 1.41,respectively),followed by a gradual decrease.There was less intraoperative bleeding in the combination anesthesia group (769 mL) than in the general anesthesia group (1200 mL)(P < 0.05).Of the 61 patients,38.8% in the general anesthesia group experienced some respiratory complication vs 6.6% in the combination anesthesia group (P < 0.001).The time to gastrointestinal tolerance was significantly correlated to the type of anesthesia,though not so the stay in critical care or the time to

关键词： Hepatectomy Epidural analgesia Perioperative complications Epidural hematoma Multimodal rehabilitation Outcomes

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Comparative study measuring the dilatory effect of a mydriatic device(Mydriasert~) versus topical drops

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International Journal of Ophthalmology(English edition) 2013年第6期6卷 801-804页

作者： manuel Saenz-de-Viteri Patricia Fernandez-Robredo Elisa de Nova Elvira Bonet-Farriol Alfonso L.Sabater Javier Zarranz-Ventura Josemaria Caire Luis M.Sadaba Angel salinas-Alaman Alfredo Garcia-Layana Department of Ophthalmology University of Navarra

AIM:To compare the mydriatic efficacy of an ophthalmic insert(Mydriasert,MY)versus phenylephrine and tropicamide(PT)eye drops.METHODS:Two controlled,prospective,randomized,single-blind studies were performed.In the first study,a total of 80 eyes from 40 outpatient-clinic patients were analyzed.PT drops were applied to the right eye,and a MY device was inserted in the left eye for 30min.Time until maximal pupil dilation for each eye was then assessed.In the second study,80 eyes from 80 patients undergoing cataract surgery were analyzed.Pupil dilation was achieved using either PT drops three-times for one hour prior to surgery(40 patients),or a MY device was inserted one hour prior to surgery(40 patients).RESULTS:In the first study,MY achieved superior mydriasis compared to PT eye drops at 90min(9.04±1.33mm vs 8.78±1.37mm,P=0.012).However MY took longer than PT drops to achieve maximal dilation,and mydriasis was inferior in eyes with MY compared to PT drops at 30min(7.21±1.73mm vs 8.22±1.43mm,P<0.001),the two groups only becoming similar by 60min(8.85±1.44mm vs 8.71±1.27mm,P=0.236).In the second study,both MY and PT achieved similar levels of mydriasis at the beginning of surgery(8.75±0.76mm with MY vs 8.77±0.63mm with PT),and also at the end of surgery(7.96±1.06mm with MY vs 8.32±0.72mm with PT),with no significant difference between groups(P=0.08).MY was well tolerated and cardiovascular effects were not influenced by dilation method.CONLUSION:MY could be a safe and efficacious alternative for mydriasis.The mydriatic effect of MY is as good as conventional PT eye drops after 60min,and is superior after 90min.MY also maintains good pupil dilation during cataract surgery.

关键词： Mydriasert~ mydriasis pupil dilation cataract surgery device

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