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Oxidative stress,the blood-brain barrier and neurodegenerative diseases:The critical beneficial role of dietary antioxidants

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Acta Pharmaceutica Sinica B 2023年第10期13卷 3988-4024页

作者： Jin Feng Youle Zheng Mingyue Guo Irma Ares mar.a martínez Bernardo Lopez-Torres mar.a-Rosa martínez-Larran aga Xu Wang Arturo Anadon mar.a-Aranzazu martínez National Reference Laboratory of Veterinary Drug Residues(HZAU)and MAO Key Laboratory for Detection of Veterinary Drug Residues Huazhong Agricultural UniversityWuhan 430070China MAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products Huazhong Agricultural UniversityWuhan 430070China Department of Pharmacology and Toxicology Faculty of Veterinary MedicineUniversidad Complutense de Madrid(UCM)And Research Institute Hospital 12 de Octubre(i+12)Madrid 28040Spain

In recent years,growing awareness of the role of oxidative stress in brain health has prompted antioxidants,especially dietary antioxidants,to receive growing attention as possible treatments strategies for patients with neurodegenerative diseases(NDs).The most widely studied dietary antioxidants include active substances such as vitamins,carotenoids,flavonoids and *** antioxidants are found in usually consumed foods such as fresh fruits,vegetables,nuts and oils and are gaining popularity due to recently growing awareness of their potential for preventive and protective agents against NDs,as well as their abundant natural sources,generally non-toxic nature,and ease of long-term *** review article examines the role of oxidative stress in the development of NDs,explores the‘two-sidedness’of the blood-brain barrier(BBB)as a protective barrier to the nervous system and an impeding barrier to the use of antioxidants as drug medicinal products and/or dietary antioxidants supplements for prevention and therapy and reviews the BBB permeability of common dietary antioxidant suplements and their potential efficacy in the prevention and treatment of ***,current challenges and future directions for the prevention and treatment of NDs using dietary antioxidants are discussed,and useful information on the prevention and treatment of NDs is provided.

关键词： Dietary antioxidant supplements Oxidative stress Blood-brain barrier Neurodegenerative diseases Vitamins Carotenoids Flavonoids Polyphenols

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Characterization and QTL identification in eggplant introgression lines under two N fertilization levels

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Horticultural Plant Journal 2023年第5期9卷 971-985页

作者： Elena Rosa-martínez Gloria Villanueva Ahmet Sahin Pietro Gramazio mar.a Dolores García-martínez mar.a Dolores Raig on Santiago Vilanova Jaime Prohens mariola Plazas Instituto de Conservacion y Mejora de la Agrodiversidad Valenciana Universitat Politecnica de ValenciaCamino de Vera 1446022 ValenciaSpain Instituto de Biología Molecular y Celular de Plantas Consejo Superior de Investigaciones Científicas-Universitat Politecnica de ValenciaCamino de Vera 1446022 ValenciaSpain

Lowering nitrogen inputs is a major goal for sustainable *** the present study,a set of 10 Solanum melongena introgression lines(ILs)developed using Solanum incanum as the exotic donor parent were grown under two nitrogen fertilization doses supplied with the irrigation system:1)8.25 mmol·L-1NH4NO3,corresponding to the high nitrogen treatment(HN),and 2)no external nitrogen supply,corresponding to the low nitrogen treatment(LN).Twenty traits,including plant growth and yield parameters,fruit size and morphology,nitrogen and carbon content in leaf and fruit,and phenolics content in fruit,were *** aim was to select of potential materials for eggplant breeding under low N inputs,as well as to identify and locate putative QTLs associated with the traits *** significant differences were observed between the soil characteristics of the HN and LN treatments,except for nitrogen and iron content,which was slightly lower in the HN,probably as a consequence of higher nutrient removal from soil by plants in the latter *** of variance showed that lowering nitrogen inputs did not significantly affect the final yield,fruit morphology,size and phenolics *** agronomic traits were highly and positively correlated with each other under both treatments,as well as total phenolics with chlorogenic acid *** assessment of the differences between each IL and the recipient parent resulted in the identification of 36 QTLs associated with most of the traits—12 were specific to the HN,17 specific to the LN,and 7 were stable across *** introgressed fragment of *** generally had a negative effect on the trait,except for QTLs for fruit dry matter,for fruit length on chromosome 10 under the HN,and for fruit pedicel length on chromosome 9 under the *** increase over AN-S-26 of the allele of *** for the QTLs detected ranged between-73.98% and 26.03% in HN and-73.67%and 34.43% in *** findings provide useful tools fo

关键词： Solanum melongena Solanum incanum Wild relatives N fertilization Abiotic stress QTL

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Pancreatic adenosquamous carcinoma and intraductal papillary mucinous neoplasm in a CDKN2A germline mutation carrier

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World Journal of Gastrointestinal Oncology 2017年第9期9卷 390-396页

作者： Fernando martínez de Juan mar.a Reolid Escribano Carmen martínez Lapiedra Fernanda Maia de Alcantara mar.a Caballero Soto Ana Calatrava Fons Isidro Machado Gastroenterology and Digestive Endoscopy Department Valencian Institute of Oncology Digestive Surgery Department Valencian Institute of Oncology Pathology Department Valencian Institute of Oncology

A 69-year-old woman from a kindred with familial atypical multiple mole melanoma and carrier of a germline mutation in CDKN2A, presented with abdominal pain caused by a solid-cystic pancreatic mass. The patient had an abdominal computed tomography three years before in which there was no evidence of pancreatic lesion. The endoscopic ultrasound guided fine needle aspiration showed adenocarcinoma with squamous component. After surgical resection the final diagnosis was adenosquamous pancreatic carcinoma(ASPC) arising in an intraductal papillar mucinous neoplasm(IPMN). Adenosquamous carcinomas are uncommon in the pancreas and have rarely been described in association with IPMNs. It has worse prognosis than the ordinary pancreatic ductal adenocarcinoma and some distinct features. We review the clinical, imaging, pathologic and molecular aspects of ASPC. Differential diagnosis with contamination, squamous metaplasia and pancreatic metastases from a distant squamous carcinoma is discussed. Besides, the case is an accelerated model of the adenoma(IPMN)-carcinoma sequence probably due to the CDKN2A ger-mline mutation. Somatic CDKN2A mutations are commonevents in the early steps of sporadic pancreatic cancer, but germline mutation carriers have a significantly higher risk of pancreatic carcinoma.

关键词： Intraductal papillary mucinous neoplasia Melanoma-pancreatic cancer syndrome Adenosquamous carcinoma Pancreatic carcinoma CDKN2A

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Inflammatory status in human hepatic cirrhosis

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World Journal of Gastroenterology 2015年第41期21卷 11522-11541页

作者： mar.a martínez-Esparza mar.a Tristán-Manzano Antonio J Ruiz-Alcaraz Pilar García-Penarrubia Departamento de Bioquímica Biología Molecular (B) e Inmunología Facultad de Medicina IMIB Regional Campus of International Excellence "Campus Mare Nostrum" Universidad de Murcia

This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus(HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcoholinduced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis(HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared withHCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counter

关键词： Inflammation Macrophages Cirrhosis Alcohol Hepatitis C virus Cytokines Liver

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Activation of Wnt/β-catenin signaling in abdominal aortic aneurysm:A potential therapeutic opportunity?

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Genes & Diseases 2023年第3期10卷 639-642页

作者： Lídia Puertas-Umbert Saray Varona Carme Ballester-Servera Judith Alonso Silvia Aguiló mar Orriols Ernesto martínez-martínez Antonio Rodríguez-Sinovas Josémartínez-González Cristina Rodríguez Institut de Recerca Hospital de la Santa Creu i Sant Pau(IRHSCSP) Barcelona 08025Spain Instituto de Investigación Biomédica Sant Pau Barcelona 08036Spain CIBER de Enfermedades Cardiovasculares ISCIIIMadrid 28029Spain Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas(IIBB-CSIC) Barcelona 08036Spain Facultad de Medicina Universidad Complutense de MadridInstituto de Investigación Sanitaria Gregorio MarañónMadrid 28040Spain Cardiovascular Diseases Research Group Vall d’Hebron Institut de RecercaVall d’Hebron Hospital UniversitariVall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain

Abdominal aortic aneurysm (AAA) is a common degenerative vascular disease with a prevalence up to 8% in males over 60 years of age.1 This is a complex disorder characterized by permanent and focal dilation of abdominal aorta that exceeds at least 50% of the normal diameter. In these patients, the aortic diameter progressively expands boosted by smoking and aging as major risk factors. Unfortunately, aneurysm growth increases the risk of aortic rupture, a life-threatening emergency that carries a mortality rate of 80%. Despite the increasing effort of the scientific community to identify therapeutic strategies for AAA, there are currently no pharmacological tools that ameliorate aneurysm expansion, while the underlying mechanisms involved in this disease are not completely understood.

关键词： aneurysm aortic therapeutic

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Forage offering and seasonal intake comparisons to evaluate European rabbit threat in Nothofagus forests of southern Patagonia

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Ecological Processes 2022年第1期11卷 604-617页

作者： Alejandro Huertas Herrera Mónica Toro‑Manríquez Laura Borrelli mar.a Vanessa Lencinas Guillermo martínez Pastur Centro de Investigación en Ecosistemas de la Patagonia(CIEP) Camino Baguales s/n Km 4CoyhaiqueChile Ulterarius Consultores Ambientales y Científicos Ltda. Ignacio Serrano 420CoyhaiqueChile Instituto Nacional de Tecnología Agropecuaria(INTA) EEA BarilocheModesta Victoria 44508400 San Carlos de BarilocheRío NegroArgentina Laboratorio de Recursos Agroforestales Centro Austral de Investigaciones Científicas(CADIC)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Houssay 2009410 UshuaiaTierra del FuegoArgentina.

Background:The European rabbit(Oryctolagus cuniculus L.1758)was introduced into different regions of the world,generating significant trade‑offs that critically impacted native ***,we evaluate the rabbit’s forage intakes in three vegetation types(forests,shrublands,and grasslands)along the four seasons in a temperate forest landscape in Southern Patagonia and discuss the potential threats over native *** formulated the following questions:(i)what is the forage offer at each vegetation type?(ii)what is the rabbit’s forage intake and how it varied across the seasons along the year?and(iii)which vegetation types and plant life forms were more used according to the rabbit’s forage intakes?Methods:We censused understory vegetation to characterize the forage offer at each vegetation type and determined seasonal dietary intakes using microhistological analysis of *** plant species identified in the field were grouped according to life form classes(tree regeneration,shrubs,forbs,graminoids,orchids,ferns,bryophytes,and hemiparasites).Data were analysed through uni‑and multi‑variate analyses,determining relationships between forage offer and the rabbit’s forage ***:Forage intakes revealed changes in plant life form consumption across vegetation types,where intake pressure was considerably different for tree regeneration(p=0.001),graminoids(p=0.001),and hemiparasites(p=0.001).Besides,significant changes in consumption among seasons were detected for shrubs(p=0.001),ferns(p=0.030),and hemiparasites(p=0.002).Although many species play an important role in the rabbit’s forage intake networks(e.g.,Chiliotrichum diffusum,Holcus lanatus),the strongest intake linkages were found in exotic grasses(e.g.,Poa pratensis and Festuca sp.),native hemiparasites(e.g.,Misodendrum sp.),native shrubs(e.g.,Empetrum rubrum),and native trees(e.g.,Nothofagus sp.).The summer and autumn seasons presented higher intake compared to the winter and spring seasons.F

关键词： Forest ecology Oryctolagus cuniculus Plant-animal interaction Vegetation type Herbivory Habitat use

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémartínez-Hernández Alejandro martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-martínez mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Rheological and tribological approaches as a tool for the development of sustainable lubricating greases based on nano-montmorillonite and castor oil

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Friction 2021年第2期9卷 415-428页

作者： Jose Enrique martÍN-ALFONSO mar.a Jose martÍN-ALFONSO Concepción VALENCIA mar.a Teresa CUBERES Department of Chemical Engineering and Materials Science Campus de“El Carmen”University of HuelvaChemical Product and Process Technology Research Center(Pro2TecS)Huelva 21071Spain Department of Applied Mechanics and Project Engineering University of Castilla-La ManchaAlmadén 13400Spain

This study investigates the development of novel montmorillonite/castor oil blends to formulate sustainable lubricating greases to promote the replacement of petrochemicals industry-derived materials by substances obtained from renewable ***,the effect of the thickener concentration on the rheological,chemical,thermal,tribological properties,and atomic force microscopy(AFM)microstructure of these systems were *** results showed that the C20A nanoclay content could be used to modulate the viscosity values,the linear viscoelastic functions,and tribological properties of these montmorillonite *** general,these gel-like dispersions exhibited remar.able lubricant properties;the samples showed values of the friction coefficient and wear scars similar or lower than those obtained with model bentonite grease.

关键词： lubricating greases nanoclay vegetable oil rheology tribology

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Metformin and colorectal cancer

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BIOCELL 2022年第1期46卷 51-59页

作者： GASTÓN AMABLE EDUARDO martÍnez-LEÓN mar.a E.PICCO OSVALDO REY Consejo Nacionalde Investigaciones Científicas y Técnicas Universidad de Buenos AiresInstituto de InmunologíaGenética y MetabolismoFacultadde Farmacia y BioquímicaHospital de Clínicas“Joséde San Martín”Ciudad Autónoma de Buenos AiresCP1120Argentina

Colorecal cancer(CRC)is one of the main causes of cancer-related mortality in the deweloped world despite recent developments in detection and treatment Several epidemiologial studis indicate that metformin,a widdy prescribed antidiabetic drug,exerts a protective effect on different cancers incuding ***,a recent double blind placebo controlled,randomized trial showed that metformin significantly decreased colorectal adenoma *** exploring the medhanism of action of metformin in cells derived from different types of ancers reported many efects including rapiratory chain complex 1 inhibition,Akt phosphorylation inhibition,ATP depltion,PKA activation and Wnt signaling ***,many of these results were obtained employing metformin at concentrations several fold higher than those achieved in target tissuas in diabetic patients receiving therapeutic recommended doses of *** contrast,recent studies obtained with metformin at concentrations compatible with those detected in human intestins revealed that metformin dicit responses that targetβ-catenin,PI3KAkt,E-adherin,pl20-catenin and focal adhesion kinase which are key molecules and signaling pathways associated to colorectal cancar *** brief review revisit several know aspects as well as nowd ones on the effects of metformin on cancer cells.

关键词： Metformin β-Catenin E-Cadherin Colorectal cancer AMPK PI3K/AKT FAK

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Global evolution of Equidae and Gomphotheriidae from South America

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Integrative Zoology 2014年第4期9卷 434-443页

作者： JoséL.prado mar.a T.ALBERDI INCUAPA CONICET-UNICENNational University of Central Buenos Aires ProvinceOlavarríaArgentina Department of Paleobiology Museo Nacional de Ciencias NaturalesCSICMadridSpain

The contemporary South American mammalian communities were determined by the emergence of the Isthmus of Panama and by the profound climatic oscillations during the *** and gomphotheres were 2 very conspicuous groups of immigrant mammals from North America that arrived in South America during the *** present study compiles updated data on the phylogeny,systematics and ecology of both groups in South *** horses in South America are represented by 2 genera,Hippidion and Equus,as are the gomphotheres,represented by Cuvieronius and *** genera of horses include small(Hippidion devillei,***,*** and ***)and large forms(Equus neogeus and ***),which dispersed into South America using 2 different *** possible model for this dispersion indicates that the small forms used the Andes corridor,while larger horses dispersed through the eastern route and through some coastal *** the case of gomphotheres,Cuvieronius and Stegomastodon reached South America in 2 independent dispersal events,and Cuvieronius dispersed across the Andean corridor,while large Stegomastodon spread along the eastern *** and gomphotheres present values ofδ^(13)C from woodlands to C4 grass*** present lower values ofδ^(13)C than Equus in the late Pleistocene,whereas the gomphotheres diverge from value ofδ^(18)O,reflecting that Cuvieronius inhabited the Andean corridor and Stegomastodon dispersed through eastern *** gomphothere and horse species recorded in South America became extinct around the time that humans arrived.

关键词： Equidae Gomphotheriidae Plio-Pleistocene South America

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