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Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration

Neural Regeneration Research 2023年第6期18卷 1196-1202页

作者： Instituto de Salud Carlos III Irene Villalón-garcía Suleva Povea-Cabello MónicaÁlvarez-Córdoba Marta Talaverón-Rey Juan MSuárez-Rivero Alejandra Suárez-Carrillo Manuel Munuera-Cabeza Diana Reche-lópez Paula Cilleros-Holgado Rocío Piñero-Pérez JoséA.Sánchez-Alcázar Centro Andaluz de Biología del Desarrollo(CABD-CSIC-Universidad pablo de Olavide de Sevilla) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos IIISevillaSpain

lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation disorders.Mitochondrial dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these disorders.Currently,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is unclear.In this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular function.The vicious cycle established between both pathological alterations may lead to the development of neurodegeneration.Therefore,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict neurodegeneration.In addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in PlA2g6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.

关键词： 4-hidroxynonenal ferroptosis iron lipid peroxidation lipofuscin neurodegeneration neurodegeneration with brain iron accumulation oxidative stress PlA2g6-associated neurodegeneration

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Pleistocene history of Iberomys,an endangered endemic rodent from southwestern Europe

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Integrative Zoology 2014年第4期9卷 481-497页

作者： gloria CUENCA-BESCÓS Juan Manuel lÓpez-gARCÍA María Angeles gAlINDO-PEllICENA Rosa gARCÍA-PEREA Julio gISBERT Juan ROFES Jacint VENTURA Research group Aragosaurus-IUCA PaleontologyEarth Sciences DepartmentUniversity of ZaragozaZaragozaSpain Research group of Paleobiology and Prehistory Human Studies DepartmentUniversity of FerraraFerraraItaly Research Institute of Evolution and Human Behavior UCM-ISCIIIMadridSpain gAlEMIA Conservation and Study of Forgotten VertebratesMadridSpain Department of Stratigraphy and Paleontology Faculty of Sciences and TechnologyUniversity of the Basque CountryGipuzkoaGuipúzcoaSpain Department of Animal Biology Plant Biology and EcologyFaculty of BiosciencesUniversity Autonoma de BarcelonaBarcelonaSpain

The extant Cabrera’s vole,Microtus cabrerae,differs in morphology and evolutionary history from the other species of Microtus.This arvicoline has unique derived features in the cranium,mandible and dentition.Probably its most conspicuous features are its large size,the high skull in lateral view,the long and distally broad nasals,and the triangle shape of the anteroconid complex,with a marked labio-lingual asymmetry of the occlusal surface of the first lower molars.In this study,we propose a phylogenetic lineage that includes Cabrera’s vole in what until now has been the Microtus subgenus Iberomys.Paleontological information and several life history traits support the elevation of Iberomys to the rank of genus.genus Iberomys comprises species that have appeared in succession during the Quaternary:in the Early Pleistocene,the extinct I.huescarensis in the Middle Pleistocene,the extinct I.mediterraneus and in the late Pleistocene,the extant I.cabrerae.Interestingly,the extant species shows several biological singularities,such as multiple polymorphic copies of the SRY male-specific gene in both males and females,and the lowest basal metabolic rate in relation to weight among arvicoline species.likewise,its habitat requirement is unique among the Iberian arvicolines.Accordingly,the biological and paleontological data that we present in this work support the elevation of its taxonomic rank to that of genus.This study also suggests a modification of nomenclature:Microtus(Iberomys)brecciensis is replaced with I.mediterraneus and the common name of the extant M.(I.)cabrerae changed from‘topillo’to‘iberon’to improve conservation and protection actions.

关键词： Cabrera’s vole conservation Iberoccitanian endemism Iberomys origin

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Acceptance of living liver donation among medical students: A multicenter stratified study from Spain

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World Journal of gastroenterology 2016年第25期22卷 5800-5813页

作者： Antonio Ríos Ana Isabel lópez-Navas Ana Isabel lópez-lópez Francisco Javier gómez Jorge Iriarte Rafael Herruzo gerardo Blanco Francisco Javier llorca Angel Asunsolo Pilar Sánchez-gallegos Pedro Ramón gutiérrez Ana Fernández María Teresa de Jesús laura Martínez-Alarcón Alberto lana lorena Fuentes Juan Ramón Hernández Julio Virseda José Yelamos José Antonio Bondía Antonio Miguel Hernández Marco Antonio Ayala pablo Ramírez Pascual Parrilla International Collaborative Donor Project ('Proyecto Colaborativo Internacional Donante' 30007 Casillas Murcia Spain Department of Surgery Paediatrics Obstetrics and Gynaecology University of Murcia Avenida de las Fuerzas Armadas 30800 Espinardo Murcia Spain Transplant Unit Surgery Service IMIB - Virgen de la Arrixaca University Hospital Carretera Madrid-Cartagena s/n 30120 El Palmar Murcia Spain Regional Transplant Centre Consejeria de Sanidad y Consumo de la Region de Murcia 30008 Ronda de Levante Murcia Spain Hospital Clinico Universitario Virgen de la Arrixaca Departamento de Cirugia General y del Aparato Digestivo Unidad de Trasplantes 30007 Casillas Murcia Spain Department of Psychology Universidad Catolica San Antonio (UCAM) Avenida de los Jeronimos 30107 Guadalupe Murcia Spain Department of Urology San Juan University Hospital of Alicante 03010 Calle Pintor Baeza Alicante Spain Universidad de granada Avenida del Hospicio s/n 18010 Granada Spain Universidad de Navarra Campus Universitario 31080 Pamplona Navarra Spain Universidad Autonoma de Madrid Ciudad Universitaria de cantoblanco 28049 Madrid Spain Servicio de Cirugia HBP y Trasplante Hepatico Complejo Hospitalario Universitario de Badajoz Hospital Infanta Cristina Avenida Elvas s/n 06006 Badajoz Spain Universidad de Cantabria Avenida los Castros s/n 39005 Santander Cantabria Spain Departamento de Cirugia Ciencias Medicas y Sociales Facultad de Medicina y Ciencias de la Salud Universidad de Alcala Campus Cientifico-Tecnologico Plaza de San Diego s/n 28801 Alcala de Henares Madrid Spain Facultad de Medicina Universidad de Malaga 29071 Avenida de Cervantes Malaga Spain Servicio de Urologia (Complejo Hospitalario Universitario de Canarias CHUC) y Departamento de Cirugia (Universidad de La Laguna ULL) Calle Molinos de Agua s/n 38207 San Cristobal de La Laguna Santa Cruz de Tenerife Spain Departamento de Ciencias Biomedicas Basicas Facultad de Ciencias Biomedicas Universidad Europea de

AIM: To analyze the attitude of Spanish medical students toward living liver donation(llD) and to establish which factors have an influence on this attitude.METHODS: Study type: A sociological, interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain(n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire(PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student′s t test, χ2 test and logistic regression analysis.RESUlTS: The completion rate was 95.7%(n = 9275). 89%(n = 8258) were in favor of related llD, and 32%(n = 2937) supported unrelated llD. The following variables were associated with having a more favorable attitude:(1) age(P = 0.008);(2) sex(P geographical area(P = 0.013);(5) believing in the possibility of needing a transplant oneself in the future(P living kidney donation(P liver segment from a family member if one were needed(P g discussed the subject with one's family(P g out activities of an altruistic nature; and(12) fear of the possible mutilation of the body after donation(P lUSION: Spanish medical students have a favorable attitude toward llD.

关键词： Attitude living liver donation Medical students Transplantation Organ donation Psychosocial variable

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Data Mining of Historic Hydrogeological and Socioeconomic Data Bases of the Toluca Valley, Mexico

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Journal of Water Resource and Protection 2016年第4期8卷 522-533页

作者： Oliver lópez-Corona Oscar Escolero Fuentes Eric Morales-Casique pablo Padilla longoria Tomás gonzález Moran Instituto de Investigación sobre Desarrollo Sustentable y Equidad Social Universidad Iberoamericana Ciudad de México México Centro de Ciencias de la Complejidad (C3) Universidad Nacional Autónoma de México Mexico City Mexico Instituto de geología Universidad Nacional Autónoma de México Ciudad de México México Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas Universidad Nacional Autónoma de México Ciudad de México México Instituto de geofísica Universidad Nacional Autónoma de México Ciudad de México México

In this paper we used several data mining techniques to analyze the coevolution of hydrogeological and socioeconomical data for the Toluca Valley in Mexico. We found non trivial relations between two historic data bases that make clear that groundwater and economy may be much more linked than it was thought before. In particular, we found that hydrogeological data trends change during economical crisis and election years in Mexico. This shows that different macroeconomical policies implemented by several administrations have a direct impact in the way groundwater is used. We also found that hydrogoelogical data evolve in the direction of population transformation from rural to urban, which could represent a whole paradigm shift in groundwater management with profound repercussions in policy making.

关键词： Data Mining Economy Data Science groundwater

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在经历 transcatheter 的病人的 atrial 纤维性颤动的临床、预示的含意大动脉的阀门培植

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World Journal of Cardiology 2012年第1期4卷 8-14页

作者： pablo Salinas Raúl Moreno luis Calvo Santiago Jiménez-Valero guillermo galeote Angel Sánchez-Recalde Teresa lópez-Fernández Sergio garcia-Blas Diego Iglesias luis Riera Isidro Moreno-gómez Jose María Mesa Ignacio Plaza Rocio Ayala Rosa gonzalez José-luis lópez-Sendón Division of Interventional Cardiology University Hospital La Paz Unit of Echocardiography University Hospital La Paz Department of Cardiology University Hospital La Paz Vascular Surgery University Hospital La Paz Department of Cardiac Anaesthesia University Hospital La Paz Cardiac Surgery University Hospital La Paz Department of Cardiology Hospital Infanta Sofia Department of Cardiology Hospital de la Cruz Roja

AIM: To study a cohort of consecutive patients under-going transcatheter aortic valve implantation (TAVI) and compare the outcomes of atrial fibrillation (AF) patients vs patients in sinus rhythm (SR). METHODS: All consecutive patients undergoing TAVI in our hospital were included. The AF group comprised patients in AF at the time of TAVI or with history of AF, and were compared with the SR group. Procedural, echocardiographic and follow-up variables were compared. likewise, the CHA 2 DS 2-VASC stroke risk score and HAS-BlED bleeding risk score and antithrombotic treatment at discharge in AF patients were compared with that in SR patients. RESUlTS: From a total of 34 patients undergoing TAVI, 17 (50%) were allocated to the AF group, of whom 15 (88%) were under chronic oral anticoagulation. Patients in the AF group were similar to those in the SR group except for a trend (P = 0.07) for a higher logistic EuroSCORE (28% vs 19%), and a higher prevalence of hypertension (82% vs 53%) and chronic renal failure (17% vs 0%). Risk of both stroke and bleeding was high in the AF group (mean CHA 2 DS 2-VASC 4.3, mean HAS-BlED 2.9). In the AF group, treatment at discharge included chronic oral anticoagulation in all except one case, and in association with an antiplatelet drug in 57% of patients. During a mean follow-up of 11 mo (maximum 32), there were only two strokes, none of them during the peri-procedural period: one in the AF group at 30 mo and one in the SR group at 3 mo. There were no statistical differences in procedural success, and clinical outcome (survival at 1 year 81% vs 74% in AF and SR groups, respectively, P = NS). CONClUSION: Patients in AF undergoing TAVI show a trend to a higher surgical risk. However, in our cohort, patients in AF did not have a higher stroke rate compared to the SR group, and the prognosis was similar in both groups.

关键词： Aortic stenosis Transcatheter aortic valve implantation Stroke Atrial fibrillation

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Comparison of Secnidazole and Fenbendazole for the Treatment of Asymptomatic giardia Infection in Dogs

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Veterinary Science Research 2019年第1期1卷 24-28页

作者： Jhon D Ruiz gloria P Ramírez Ana M Múnera Carlos Arroyave laura Castano pablo lópez grupo de Investigación en Ciencias de los Animales.Facultad de Medicina Veterinaria y Zootecnia.Universidad CES.Medellín Colombia

The objetive of this study was to compare a single dose of secnidazole versus multiple doses of fenbendazole for the treatment of dogs with asymptomatic giardia infection.Materials and methods:Twenty-four asymptomatic dogs with a positive test result for giardia spp were randomized in two equal groups to receive a single dose of secnidazole at 30 mg/kg PO,or fenbendazole at 50 mg/kg PO q24h for 3 days.Hematological parameters were evaluated before and 8 days after treatment,and feces were re-examined at days 8,15,and 30 post-treatment by fecal flotation and antigen test.Results:The number of positive dogs in the fenbendazole group was:1(day 8)and 3(days 15 and 30).In the secnidazole group,the number of positive cases were:4(day 8),3(day 15),and 1(day 30).Conclusion:Treatment with secnidazole or fenbendazole,were effective between 75%and 92%to eliminate the excretion of giardia cysts in canines together with hygienic measures to control,like disinfection with quaternary ammonium of patients and their environment.Further studies that include more animals and multiple fecal exams on consecutive days would be necessary to confirm its efficacy in dogs.

关键词： Drugs effects Parasitology Pharmacology Zoonosis

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Spontaneous and Bleomycin-Induced <i>γ</i>H2AX Signals in CHO9 Metaphase Chromosomes

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Advances in Bioscience and Biotechnology 2014年第7期5卷 603-616页

作者： María Vittoria Di Tomaso Silvia Basso laura lafon-Hughes gustavo Saona Beatriz lópez-Carro Ana laura Reyes-ábalos pablo liddle Environmental Quality Evaluation and Control Service Municipality of Montevideo Montevideo Uruguay genetics Department Instituto de Investigaciones Biológicas Clemente Estable Montevideo Uruguay

In eukaryotes, a cascade of events named DNA damage response (DDR) has evolved to handle DNA lesions. DDR engages the recruitment of signaling, checkpoint control, repair and chromatin remodeling protein complexes, allowing cell cycle delay, DNA repair or induction of apoptosis. An early DDR event involves the phosphorylation of the histone variant γH2AX on serine 139 (H2AX139 phosphorylation) originating the so-called γH2AX. DDR-related H2AX139 phosphorylation have been extensively studied in interphase nuclei. More recently, γH2AX signals on mitotic chromosomes of asynchronously growing cell cultures were observed. We performed a quantitative analysis of γH2AX signals on γH2AX immunolabeled cytocentrifuged metaphase spreads, analyzing the γH2AX signal distributions of CHO9 chromosomes harboring homologous regions both in control and bleomycin (BlM)-treated cultures. We detected γH2AX signals in CHO9 chromosomes of controls which significantly increase after BlM-exposure. γH2AX signals were uniformly distributed in chromosomes of controls. However, the γH2AX signal distribution in BlM exposed cells was significantly different between chromosomes and among chromosome regions, with few signals near the centromeres and a tendency to increase towards the telomeres. Interestingly, both basal and BlM-induced γH2AX signal distribution were statistically equal between CHO9 homologous chromosome regions. Our results suggest that BlM exerts an effect on H2AX139 phosphorylation, prevailing towards acetylated and gene-rich distal chromosome segments. The comparable H2AX139 phosphorylation of homologous regions puts forward its dependence on chromatin structure or function and its independence of the position in the karyotype.

关键词： H2AX Phosphorylation on Serine 139 γH2AX Signals Metaphase Chromosomes Homologous Chromosome Regions CHO9 Chinese Hamster Cell line

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Immunomodulatory oligonucleotide IMT504:Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

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World Journal of Stem Cells 2017年第3期9卷 45-67页

作者： Jorge Zorzopulos Steven M Opal Andrés Hernando-Insúa Juan M Rodriguez Fernanda Elías Juan Fló Ricardo A lópez Norma A Chasseing Victoria A lux-lantos Maria F Coronel Raul Franco Alejandro D Montaner David l Horn Immunotech S.A. Ciudad de Buenos Aires C1440FFXArgentina Infectious Disease Division Memorial Hospital of Rhode Island and Alpert Medical SchoolProvidenceRI 02905United States Fundación pablo Cassara Ciudad Autonoma de Buenos Aires C1440FFXArgentina Instituto de Biología y Medicina Experimental(IBYME-CONICET) Ciudad Autónoma de Buenos Aires C1428ADNArgentina Instituto de Ciencia y Tecnolog'DR.Cesar Milstein” Fundación Pablo CassaráCiudad Autonoma de Buenos Aires C1440FFXArgentina David Horn llC DoylestownPA 18902United States

The immune responses of humans and animals to insults(i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged proinflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell(MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

关键词： Immunohomeostasis Immunoprotection Immunoregeneration Inflammation Mesenchymal stem cells IMT504

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A Novel Classification of Brain Invasion in Malignant Ethmoidal Tumors and Management Proposal

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International Journal of Otolaryngology and Head & Neck Surgery 2019年第5期8卷 151-165页

作者： Joel Caballero-garcía Nélido gonzáles-Fernández Pedro pablo Morales-Hechevarría Carlos Aparicio-garcía Misael lópez Sánchez Juvenal Huanca-Amaru National Institute of Oncology and Radiobiology La HabanaCuba

Object: Brain invasion is unusual in patients with paranasal sinuses cancer. Staging systems do not specify brain invasion extension who has an impact in therapeutic strategy and prognosis. Surgical series of this patient treated by endonasal endoscopic approach are scarce. In this paper, a novel classification and surgical strategy is proposed. Methods: A retrospective review of patients with ethmoidal malignant tumors with brain invasion treated at the National Institute of Oncology and Radiobiology from January 2015 to October 2017 by means endonasal endoscopic surgery was performed. All medical records were reviewed for demographics, diagnoses, presentation, endoscopic approach, reconstructive techniques and clinical outcomes. Pattern of brain invasion was classified in five grades. Chi-squared test, ANOVA test and Kaplan-Meier curves were used. Results: Forty-seven patients (26 males and 21 females) were registered. Mean age was 52.3 years ± 27.0. Only 3 patients presented with neurologic symptoms. Histologic subtypes were squamous cell carcinoma (25 patients), adenocarcinoma (16 patients), and esthesioneuroblastoma (6 patients). Five patients corresponded to grade I, 39 grade II and 3 grade III. The mean surgical time was 351.9 min (±45). The mean blood loss was 704.5 ml (±206). The mean ICU stay was 1.1 (ranging from 1 to 2 ) days and the hospital stay was 5.3 (ranging from 5 to 7) days. Conclusions: Brain invasion represents a particular therapeutic challenge in patients with malignant nasosinusal tumors. Surgical treatment is possible in some cases, including endonasal endoscopic approach. A stage classification of brain invasion helps to establish an optimal surgical strategy and a prognosis.

关键词： Sinunasal Cancer Brain Invasion Endoscopic Surgery

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Development of an Infusion Based on Romaine lettuce and Banana for Treating Insomnia

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Agricultural Sciences 2020年第6期11卷 529-539页

作者： Daniel Revelo-Cáceres María Jesús Oliveras-lópez Marina Villalón-Mir Miguel Navarro-Alarcón Herminia lópez-garcía de la Serrana Facultad de Farmacia Universidad de Granada Granada Espa&#241 a Departamento de Biología Molecular e Ingeniería Bioquímica Universidad Pablo de Olavide Sevilla Espa&#241 a

An infusion was developed based on green romaine lettuce leaves and banana. Further, its sensorial acceptability was evaluated as a possible alternative treatment for insomnia. The romaine lettuces and bananas used were washed, chopped, dehydrated and ground. Optimal lettuce dehydration time was determined through charting the weight lost and examining the curve. This was found after 180 minutes at 60°C. Two formulas were developed, the first with 1.1 g of dehydrated romaine lettuce and 0.2 g of dehydrated banana, and the second with 1.1 g of dehydrated romaine lettuce and 0.4 g of dehydrated banana. Sensory analysis was conducted using sorting tests for taste, aroma, paired preferences and intention to purchase. Tasters preferred the formula with a lower quantity of dehydrated banana. 85% of tasters indicated that they would buy this infusion due to its potential functional properties for overcoming insomnia.

关键词： Infusion Romaine lettuce Banana Insomnia Sensory Analysis

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