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Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease

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Neural Regeneration Research 2019年第9期14卷 1626-1634页

作者： Edwin E. Reza-Zaldivar Mercedes A. Hernández-Sapiéns Yanet K. Gutiérrez-Mercado Sergio Sandoval-ávila Ulises Gomez-Pinedo Ana L. Márquez-Aguirre Estefanía Vázquez-Méndez Eduardo Padilla-Camberos Alejandro A. Canales-Aguirre Unidad de Evaluation Preclinica Unidad de Biotecnologia Medica y FarmaceuticaCentro de Investigation y Asistencia en Tecnologia y Diseno del Estado de JaliscoGuadalajaraMexico Regenerative Medicine Unit Neuroscience InstituteDepartment of Neurosurgery and NeurologyIdlSSC Health Research Institute of the Hospital Clinico San CarlosMadridSpain

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.

关键词： Alzheimer’s disease neurodegenerative disease cognitive impairment memory Alzheimer’s disease mouse model mesenchymal stem cell exosomes neurogenesis cognitive improvement cell-free therapy neural regeneration

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Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease

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Neural Regeneration Research 2022年第1期17卷 31-37页

作者： Mercedes A.Hernández-Sapiéns Edwin E.Reza-Zaldívar Ana L.Márquez-Aguirre ulises Gómez-pinedo Jorge Matias-Guiu Ricardo R.Cevallos Juan C.Mateos-Díaz Víctor J.Sánchez-González Alejandro A.Canales-Aguirre Unidad de Evaluación Preclínica Unidad de Biotecnología Médica y FarmacéuticaCentro de Investigación y Asistencia en Tecnología y Diseño del Estado de JaliscoGuadalajaraMéxico Instituto de Neurociencias IdISSCHospital Clínico San CarlosMadridEspaña Biochemistry and Molecular Genetics Department University of AlabamaBirminghamAlabama Unidad de Biotecnología Industrial Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de JaliscoGuadalajaraMéxico Centro Universitario de los Altos Universidad de GuadalajaraGuadalajaraMéxico

The presenilin genes(PSEN1 and PSEN2)are mainly responsible for causing early-onset familial Alzheimer’s disease,harboring~300 causative mutations,and representing~90%of all mutations associated with a very aggressive disease form.Presenilin 1 is the catalytic core of theγ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein,Notch-1,N-and E-cadherin,LRP,Syndecan,Delta,Jagged,CD44,ErbB4,and Nectin1a.Presenilin 1 plays an essential role in neural progenitor maintenance,neurogenesis,neurite outgrowth,synaptic function,neuronal function,myelination,and plasticity.Therefore,an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling,synaptic dysfunction,memory impairment,and increased Aβ42/Aβ40 ratio,contributing to neurodegeneration during the initial stages of Alzheimer’s disease pathogenesis.This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer’s disease.Furthermore,we emphasize the importance of Alzheimer’s disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer’s disease pathogenesis throughout neuronal differentiation impairment.

关键词： familial Alzheimer’s disease familial Alzheimer’s disease-induced pluripotent stem cells models induced pluripotent stem cells neurogenesis neuronal differentiation Notch presenilin 1 PSEN1 mutations γ-secretase complex

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Fulminant Hepatitis Associated with Chronic Consumption of 3,4-Methylenedioxy-Methamphetamine;Case Report

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Open Journal of Gastroenterology 2024年第5期14卷 161-166页

作者： ulises Solis gomez Gustavo Adolfo Hernández Valdez Juan Antonio Contreras Escamilla Ivan Alejandro Medina Jimenez Jorge Morales Rojas Jocelyn Nataly Quintero Melendez Marco Antonio González Villar Department of Internal Medicine ISSSTE APP General Hospital of Tepic Tepic Nayarit Mexico

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).

关键词： Fulminant Hepatitis Acute Liver Failure Methamphetamine Severe Acute Liver Failure in a User of Drugs of Abuse Hepatology

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复发性卒中与大麻的使用有关

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世界核心医学期刊文摘（神经病学分册） 2005年第7期1卷 30-30页

作者： Mateo I. pinedo A. gomez-Beldarrain M. J.C.Garcia-Monco 赵睿 Service of Neurology Hospital de Galdacano48960 Galdacano Vizcaya Spain Dr.

Drug misuse represents a risk factor for cerebrovascular disease,especially am ong young people. Despite the fact that cannabisis the most widely used illicit drug, there are only a few reports associating its use with cerebrovascular dise ase. We describe a patient who suffered three ischaemic strokes immediately afte r cannabis consumption. Other stroke aetiologies were ruled out, and neuro imagi ng revealed infarcts in different arterial areas as well as evidence of non-ath erosclerotic arterial disease,which suggests an underlying vasculopathy of uncer tain (toxicor inflammatory) origin. Cannabis use may be associated with ischaemi c stroke in young patients,but its mechanismis unclear.

关键词：复发性卒中缺血性卒中脑血管病影像学检查 unclear 违禁药物 suffered 发病机制 young immediately

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Uremic Bleeding in 2 Patients with Dieulafoy’s Lesion: Case Report and Literature Review

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Open Journal of Gastroenterology 2024年第5期14卷 167-173页

作者： Gustavo Adolfo Hernández Valdez Diana Estefanía Ibarra García Juan Antonio Contreras Escamilla Janette Alejandra Gamiño Gutierrez Francisco Manuel Tonatiuh Carrillo Beltran ulises Solis gomez Jocelyn Nataly Quintero Meléndez Ivan Alejandro Medina Jimenez Marco Antonio González Villar Jorge Rojas Morales Department of Internal Medicine ISSSTE APP General Hospital of Tepic Tepic Nayarit Mexico Hospital Civil de Guadalajara Fray Antonio Alcalde Guadalajara Jalisco M&#233xico

Dieulafoy’s lesions are rare vascular malformations of the gastrointestinal tract. A Dieulafoy’s lesion is an aberrant vessel that does not reduce in caliber when it extends from the submucosa to the mucosa. Damage to this artery can cause severe and intermittent arterial bleeding from small vascular stumps that are difficult to visualize. Furthermore, these catastrophic bleeding episodes frequently result in hemodynamic instability and the need for transfusion of multiple blood products. Recently, uremic syndrome has been identified as a risk factor for gastric mucosal lesions. We present two clinical cases of acute digestive bleeding due to Dielafoy lesion with chronic kidney disease as the main cause, where two different therapies were performed endoscopically. We concluded with the results of our patients that the best therapy was the application of the hemostatic hemoclip on the injury vs the injection with adrenaline on the wound site. Uremia is identified as a risk factor for upper gastrointestinal bleeding in patients with pre-existing Dieulafoy’s lesion, as well as a higher incidence of new bleeding.

关键词： Dieulafoy’s Lesion Gastrointestinal Bleeding Endoscopy Endoscopy Hemostatic Clips Kidney Disease Adrenaline Thermal Coagulation Dieulafoy

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