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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-López Iva Tic David Valle-García Marta Ribalta-Vilella Luis Labrador Deb Ranjan Banerjee Ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8

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Expectations and Level of Satisfaction of the Patient with Parkinson’s Disease Undergoing Deep Brain Stimulation surgery at the national institute of neurology and neurosurgery

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Advances in Parkinson's Disease 2024年第1期13卷 1-7页

作者： Paola Bazán-Rodríguez Eduardo Ichikawa-Escamilla Etienne Reséndiz-Henríquez Carlos E. Martínez-Cortés Amin Cervantes-Arriaga Mayela Rodríguez-Violante Lisette Bazán-Rodríguez Laboratorio de Enfermedades Neurodegenerativas en el Instituto Nacional de Neurología y Neurocirugía manuel velasco suarez Ciudad de México México Laboratorio de Enfermedades Neurodegenerativas en el Instituto Nacional de Neurología y Neurocirugía manuel velasco suarez Ciudad de México México. Unidad Periférica para el Estudio de la Neuroinflamación en Patologías Neurológicas del Instituto de Investigaciones Biomédicas en el Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez Ciudad de México México

Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson’s disease (PD). Reports show continued patient satisfaction after surgery despite not maintaining clinical improvement as measured by evolution scales. Objectives: The present study sought to explore expectations and level of satisfaction in patients after DBS surgery with a semi-structured questionnaire and subsequent correlation with functional scales, Quality of Life (QoL), and motor and non-motor symptoms. Methods: We performed descriptive statistics to represent demographic data, Wilcoxon rank tests to determine significant differences, and Spearman correlation between the applied scales. Results: We evaluated 20 patients with a history of DBS surgery. 45% were female, with a mean age of 55.7 ± 14.15 years, a mean disease duration of 13.42 ± 8.3 years, and a mean time after surgery of 3.18 ± 1.86 years. Patients reported surgery meeting expectations in 85.5% and continued satisfaction in 92%. These two variables showed a significant correlation. Conclusions: This sample of patients remained satisfied after DBS surgery, although we found no differences in motor and non-motor clinimetric scales. Further studies are needed to confirm the importance of assessing quality of life in patients with DBS.

关键词： Parkinson’s Disease Quality of Life Deep Brain Stimulation Patient Satisfaction

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Numerical Simulation of the Blood Flow through a Brain Vascular Aneurysm with an Artificial Stent Using the SPH Method

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Engineering（科研） 2018年第12期10卷 891-912页

作者： Leonardo Di G. Sigalotti Jaime Klapp Karla Pedroza Edgar Nathal Carlos E. Alvarado-Rodríguez Area of Physics of Irreversible Processes Department of Basic Sciences Autonomous Metropolitan University-Azcapotzalco (UAM-A) Mexico City Mexico Physics Department National Institute of Nuclear Research (ININ) Ocoyoacac Mexico Los Cabos H+ Hospital San José del Cabo Mexico national institute of neurology and neurosurgery “manuel velasco suárez” Mexico City Mexico Departament of Chemical Engineering DCNyE University of Guanajuato Guanajuato Mexico

We present numerical simulations of blood flow through a brain vascular aneurysm with an artificial stent using Smoothed Particle Hydrodynamics (SPH). The aim of this work is to analyze how the flow into an aneurysm changes using different stent configurations. The initial conditions for the simulations were constructed from angiographic images of a real patient with an aneurysm. The wall shear stresses, pressure and highest velocity within the artery, and other particular quantities are calculated which are of medical specific interest. The numerical simulations of the cerebral circulation help doctors to determine if the patient’s own vascular anatomy has the conditions to allow arterial stenting by endovascular method before the surgery or even evaluate the effect of different stent structure and materials. The results show that the flow downstream the aneurysm is highly modified by the stent configuration and that the best choice for reducing the flow in the aneurysm is to use a completely extended Endeavor stent.

关键词： Brain Vascular Flow Aneurysms Blood Flow Particle Methods Numerical Modeling

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