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Phosphorylated tau as a toxic agent in synaptic mitochondria: implications in aging and Alzheimer’s disease

Neural Regeneration Research 2022年第8期17卷 1645-1651页

作者： Angie K.Torres Bastián I.Rivera Catalina M.Polanco claudia jara Cheril Tapia-Rojas Laboratory of Neurobiology of Aging Centro de Biología Celular y Biomedicina(CEBICEM)Facultad de Medicina y CienciaUniversidad San SebastiánSede Los LeonesSantiagoChile

During normal aging,there is a decline in all physiological functions in the *** of the most affected organs is the brain,where neurons lose their proper synaptic function leading to cognitive *** is one of the main risk factors for the development of neurodegenerative diseases,such as Alzheimer’s *** of the main responsible factors for synaptic dysfunction in aging and neurodegenerative diseases is the accumulation of abnormal proteins forming *** most studied brain aggregates are the senile plaques,formed by Aβpeptide;however,the aggregates formed by phosphorylated tau protein have gained relevance in the last years by their *** is reported that neurons undergo severe mitochondrial dysfunction with age,with a decrease in adenosine 5′-triphosphate production,loss of the mitochondrial membrane potential,redox imbalance,impaired mitophagy,and loss of calcium buffer ***,abnormal tau protein interacts with several mitochondrial proteins,suggesting that it could induce mitochondrial ***,whether tau-mediated mitochondrial dysfunction occurs indirectly or directly is still unknown.A recent study of our laboratory shows that phosphorylated tau at Ser396/404(known as PHF-1),an epitope commonly related to pathology,accumulates inside mitochondria during normal *** accumulation occurs preferentially in synaptic mitochondria,which suggests that it may contribute to the synaptic failure and cognitive impairment seen in aged ***,we review the main tau modifications promoting mitochondrial dysfunction,and the possible mechanism ***,we discuss the evidence that supports the possibility that phosphorylated tau accumulation in synaptic mitochondria promotes synaptic and cognitive impairment in ***,we show evidence and argue about the presence of phosphorylated tau PHF-1 inside mitochondria in Alzheimer’s disease,which could be considered as an early event

关键词： age pathology aging Alzheimer’s disease hippocampus memory mitochondria PHF-1 phosphorylated tau synaptic mitochondria tau

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Clinical relevance of the use of Dentoxol® for oral mucositis induced by radiotherapy: A phase II clinical trial

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World Journal of Clinical Oncology 2022年第10期13卷 813-821页

作者： Sebastián Solé Sergio Becerra claudia Carvajal Piero Bettolli Hernán Letelier Alejandro Santini Lorena Vargas Alexander Cifuentes Francisco Larsen Natalia jara Jorge Oyarzún Eva Bustamante Benjamín Martínez David Rosenberg Tomas Galván Department of Radiotherapy Radiomedicine InstituteAmérico Vespucio Norte 1314 Vitacura7630370SantiagoChile National Institute of Cancer SantiagoServicio de Salud Metropolitano NorteAv Profesor Zañartu 1010Independencia8380455SantiagoChile Oncologic Institute Arturo López Pérez Foundation JoséManuel Infante 805Providencia7500691SantiagoChile Hospital Base Valdivia Bueras 1003 s/n XIV Región5100238ValdiviaChile Oncologic Center of Antofagasta Los Pumas 10255Antofagasta1267348AntofagastaChile Universidad Mayor SantiagoAv Libertador Bernardo O´Higgins 20138340585SantiagoChile Ingalfarma Dr Manuel Barros Borgoño 71Oficina 1308Providencia7500593SantiagoChile

BACKGROUND Severe oral mucositis associated with cancer therapy is a frequent complication that may affect a patient's systemic condition,resulting in interruption and/or prolongation of cancer ***®is a medical solution in the form of a mouthwash that has been shown to result in statistically significant improvement in the prevention of severe oral ***,knowing the measures of the clinical significance of this therapy is important for accurate *** describe the clinical impact of Dentoxol®use in severe oral *** Clinical significance was measured using the results obtained in a randomized controlled clinical trial previously conducted by the same group of *** measures of clinical significance evaluated were the absolute risk or incidence,relative risk,absolute risk reduction,relative risk reduction,number needed to treat,and odds *** The data obtained show that the impact of Dentoxol®on reducing the severity of oral mucositis has important clinical *** The results of this study justify the incorporation of Dentoxol®mouth rinse into clinical protocols as a complement to cancer therapy to prevent and/or treat oral mucositis secondary to radiotherapy.

关键词： Clinical trial Dentoxol Oral mucositis Prevention Radiotherapy Treatment

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Effect of Polishing Procedure on the Roughness and Bacterial Adhesion of Provisional Restorative Materials

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Microscopy Research 2018年第2期6卷 9-18页

作者： Néstor Usiel Lara-jara Gabriel Fernando Romo-Ramírez María del Pilar Goldaracena-Azuara Antonio Aragón-Piñ a claudia Butrón-Téllez Girón María Verónica Méndez-González Ana María González-Amaro Faculty of Stomatology Autonomous University of San Luis Potosí San Luis Potosí City México Faculty of Engineering Institute of Metallurgy Autonomous University of San Luis Potosí San Luis Potosí City México Laboratory of Biochemistry Microbiology and Pathology Faculty of Stomatology Autonomous University of San Luis Potosí San Luis Potosí City México

Provisional prosthetic restoration materials are exposed to oral cavity producing on the surface biofilm where different factors such as surface roughness and porosity can condition their formation and organization and can create stagnation areas that promote the bonding of organic particles, thus facilitating the formation and maturation of the biofilm. The purpose of this study was to compare surface roughness of two provisional prosthetic restorations materials and their bacterial susceptibility. In this study, two provisional restoration materials were used in two groups, A polymethyl methacrylate acrylic (NicTone MDC DENTAL) and B bis-acryl resin (Protemp 4 ESPE 3M). A total of 80 samples (40 samples of each material) were in thick plates of 10 × 10 mm and 2 mm high. 20 samples of each material were polished, while 20 were left unpolished. Subsequently, the samples were observed by Atomic Force Microscopy for their evaluation of surface roughness. The values were analyzed with t-test, Mann-Whitney U test and Kruskal Wallis test. The samples were microbiologically inoculated with the strains obtained and identified from a provisional polymethyl methacrylate acrylic restoration in a patient, in order to observe bacterial adhesion using a Scanning Electron Microscope. Two strains, Enterococcus faecalis and Pseudomona luteola, were identified. The presence of the microorganisms was observed on the surface of both materials, either polished or unpolished, with a lower level of microorganism adhesion found on the bis-acrylic resin. There was a significant difference about surface roughness in the groups A and B with p -8). We found that the polished bis-acrylic resin showed lower surface roughness and bacterial adhesion in comparison with the polymethyl methacrylate.

关键词： Surface Analysis Bacterial Adhesion Provisional Fixed Restoration

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Joint Multi-modal Parcellation of the Human Striatum:Functions and Clinical Relevance

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Neuroscience Bulletin 2020年第10期36卷 1123-1136页

作者： Xiaojin Liu Simon B.Eickhoff Felix Hoffstaedter Sarah Genon Svenja Caspers Kathrin Reetz Imis Dogan claudia R.Eickhoff Ji Chen Julian Caspers Niels Reuter Christian Mathys Andre Aleman Renaud Jardri Valentin Riedl Iris E.Sommer Kaustubh R.Patil Institute of Neuroscience and Medicine(INM-7 Brain and Behaviour)Research Centre JiilichJiilichGermany Institute of Systems Neuroscience Heinrich Heine University DusseldorfDusseldorfGermany Institute of Neuroscience and Medicine(INM-1) Research Centre Jiilich52428 JiilichGermany Institute for Anatomy I Medical FacultyHeinrich Heine University Dusseldorf40225 DusseldorfGermany Jiilich Aachen Research Alliance-BRAIN(jara)Institute of Molecular Neuroscience and Neuroimaging Forschungszentrum JiilichRheinisch Westfallische Technische Hochschule(RWTH)Aachen University52074 AachenGermany Department of Neurology Rheinisch Westfallische Technische Hochschule(RWTH)Aachen University52074 AachenGermany Institute of Clinical Neuroscience and Medical Psychology Medical FacultyUniversity of Dusseldorf40225 DusseldorfGermany Department of Diagnostic and Interventional Radiology Medical FacultyUniversity of Dusseldorf40225 DusseldorfGermany Institute of Radiology and Neuroradiology Evangelisches KrankenhausUniversity of Oldenburg26129 OldenburgGermany Department of Neuroscience University Medical Center GroningenUniversity of Groningen9713 AV GroningenThe Netherlands SCALab(CNRS UMR9193)&CHU de LiUe Hopital FontanPole de Psychiatrie(CURE)Universite de Lille59037 LilleFrance Departments of Neuroradiology Nuclear Medicine and Neuroimaging CenterTechnische Universitat Miinchen80333 MunichGermany

The human striatum is essential for both lowand high-level functions and has been implicated in the pathophysiology of various prevalent disorders,including Parkinson's disease(PD)and schizophrenia(SCZ).It is known to consist of structurally and functionally divergent ***,previous parcellations are based on a single neuroimaging modality,leaving the extent of the multi-modal organization of the striatum ***,we investigated the organization of the striatum across three modalities—resting-state functional connectivity,probabilistic diffusion tractography,and structural covariance—to provide a holistic convergent view of its structure and *** found convergent clusters in the dorsal,dorsolateral,rostral,ventral,and caudal *** characterization revealed the anterior striatum to be mainly associated with cognitive and emotional functions,while the caudal striatum was related to action ***,significant structural atrophy in the rostral and ventral striatum was common to both PD and SCZ,but atrophy in the dorsolateral striatum was specifically attributable to *** study revealed a cross-modal convergent organization of the striatum,representing a fundamental topographical model that can be useful for investigating structural and functional variability in aging and in clinical conditions.

关键词： Striatum Multi-modal Connectivity-based parcellation Convergent clusters Voxel-based morphometry Parkinson's disease Schizophrenia

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No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors

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Translational Neurodegeneration 2019年第1期8卷 127-133页

作者： Franziska Hopfner Stefanie HMüller Dagmar Steppat Joanna Miller Nele Schmidt Klaus-Peter Wandinger Frank Leypoldt Daniela Berg Andre Franke Wolfgang Lieb Lukas Tittmann Monika Balzer-Geldsetzer Simon Baudrexel Richard Dodel Ruediger Hilker-Roggendorf Elke Kalbe Jan Kassubek Thomas Klockgether Inga Liepelt-Scarfone Brit Mollenhauer Petra Neuser Kathrin Reetz Oliver Riedel claudia Schulte Jörg BSchulz Annika Spottke Alexander Storch claudia Trenkwalder Hans-Ulrich Wittchen Karsten Witt Ullrich Wüllner Günther Deuschl Gregor Kuhlenbäumer Department of Neurology University Hospital Schleswig HolsteinArnold-Heller Str.324105 KielGermany Center of Blood Transfusion University Hospital Schleswig HolsteinKiel&LübeckGermany Department of Clinical Chemistry University Hospital Schleswig-HolsteinKielGermany Institute of Clinical Molecular Biology University Hospital Schleswig-HolsteinKielGermany Institute of Epidemiology University Hospital Schleswig-HolsteinKielGermany Chair of Geriatric Medicine University Hospital EssenEssenGermany Department of Neurology Philipps-University MarburgMarburgGermany Department of Neurology Goethe UniversityFrankfurt/MainGermany Brain Imaging Center Goethe UniversityFrankfurt/MainGermany Department of Medical Psychology|Neuropsychology and Gender Studies&Center for Neuropsychological Diagnostics and Intervention(CeNDI) University Hospital CologneCologneGermany Psychological Gerontology Institute of GerontologyUniversity of VechtaVechtaGermany Department of Neurology University of UlmUlmGermany Department of Neurology University of Bonnand German Center for Neurodegenerative Diseases(DZNE)BonnGermany Center for Neurology Hertie Institute for Clinical Brain ResearchDepartment of Neurodegenerative DiseasesUniversity of TübingenTübingenGermany DZNE German Center for Neurodegenerative DiseasesTübingenGermany Paracelsus-Elena-Klinik KasselGermany Institute of Neuropathology and Department of Neurosurgery University Medical Center GöttingenGöttingenGermany Coordinating Centre for Clinical Trials Philipps-UniversityMarburgGermany Department of Neurology RWTH Aachen UniversityAachenGermany jara-BRAIN Institute of Molecular Neuroscience and Neuroimaging Forschungszentrum Jülich GmbH and RWTH Aachen UniversityAachenGermany Leibniz Institute for Prevention Research and Epidemiology-BIPS Achterstrasse 3028359 BremenGermany Department of Neurology Technische Universität Dresden01307 DresdenGermany German Center for Neurodegenerative Diseases(DZNE) Research Site Rostock18147 RostockGerma

Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune *** examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting *** measured NMDA antibodies in a large,well phenotyped sample of Parkinson patients without and with cognitive impairment(n=296)and controls(n=295)free of neuropsychiatric *** phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive ***:NMDA antibodies were analysed in the serum of patients and controls using well established validated *** used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic ***:The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients(13%)than in controls(22%)and higher than in previous studies in both *** IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment,nor with quantitative indicators of disease severity and cognitive impairment.A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson ***:It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease *** Parkinson disease with dementia,while NMDA IgG antibodies define a separate disease of its own.

关键词： NMDA antibody NMDA IgA/IgM antibodies Parkinson disease Cognitive impairment

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