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neural Regeneration Research 2019年第10期14卷 1661-1671页

作者： Raquel Coronel Charlotte Palmer Adela Bernabeu-Zornoza maría monteagudo Andreea Rosca Alberto Zambrano Isabel Liste unidad de Regeneración neural Unidad Funcional de Investigación de Enfermedades Crónicas Instituto de Salud Carlos Ⅲ (ISCⅢ)

The pathological implication of amyloid precursor protein(APP)in Alzheimer’s disease has been widely documented due to its involvement in the generation of amyloid-β ***,the physiological functions of APP are still poorly *** is considered a multimodal protein due to its role in a wide variety of processes,both in the embryo and in the adult ***,APP seems to play a key role in the proliferation,differentiation and maturation of neural stem *** addition,APP can be processed through two canonical processing pathways,generating different functionally active fragments:soluble APP-α,soluble APP-β,amyloid-β peptide and the APP intracellular C-terminal *** fragments also appear to modulate various functions in neural stem cells,including the processes of proliferation,neurogenesis,gliogenesis or cell ***,the molecular mechanisms involved in these effects are still *** this review,we summarize the physiological functions of APP and its main proteolytic derivatives in neural stem cells,as well as the possible signaling pathways that could be implicated in these *** knowledge of these functions and signaling pathways involved in the onset or during the development of Alzheimer’s disease is essential to advance the understanding of the pathogenesis of Alzheimer’s disease,and in the search for potential therapeutic targets.

关键词： amyloid precursor protein APP soluble APP alpha soluble APP beta amyloid beta peptide APP intracellular domain neural stem cells neural progenitor cells neurogenesis signaling pathways

Use of a combination strategy to improve neuroprotection and neuroregeneration in a rat model of acute spinal cord injury

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neural Regeneration Research 2019年第6期14卷 1060-1068页

作者： Elisa García Roxana Rodríguez-Barrera Vinnitsa Buzoianu-Anguiano Adrian Flores-Romero Emanuel malagón-Axotla marco Guerrero-Godinez Estefanía de la Cruz-Castillo Laura Castillo-Carvajal monserrat Rivas-Gonzalez Paola Santiago-Tovar Ivis morales Cesar Borlongan Antonio Ibarra Centro de investigación en Ciencias de la Salud (CICSA) Facultad de Ciencias de la SaludUniversidad Anáhuac México Campus Norte Centro de investigación del Proyecto CAmInA A.C. unidad de investigación médica en enfermedades neurologicas Hospital Especialidades CMN Siglo XXI unidad de Rehabilitación Osteoarticular.Instituto nacional de Rehabilitación. Luis Guillermo Ibarra Ibarra Center of Excellence for Aging and Brain Repair Department of Neurosurgery and Brain RepairUniversity of South Florida Morsani College of Medicine

Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides(InDP), inhibition of glial scar formation(dipyridyl: DPY), as well as the use of biocompatible matrix(fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells(mSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) InDP + DPY; 4) DPY+ FG; 5) InDP + DPY + FG + mSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord(hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy(DPY+ InDP + FG+ mSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy(DPY+ InDP + FG + mSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee(approval no. 178544; CSnBTBIBAJ 090812960)on August 15, 2016.

关键词： fibrin glue mesenchymal stem cells glial scar protective autoimmunity neural derived peptides neural regeneration

Physiological and pathological effects of amyloid-β species in neural stem cell biology

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neural Regeneration Research 2019年第12期14卷 2035-2042页

作者： Adela Bernabeu-Zornoza Raquel Coronel Charlotte Palmer maría monteagudo Alberto Zambrano Isabel Liste unidad de Regeneración neural Unidad Funcional de Investigación de Enfermedades Crónicas. Instituto de Salud Carlos Ⅲ(ISCⅢ) Majadahonda Madrid Spain

Although amyloid-β peptide is considered neurotoxic, it may mediate several physiological processes during embryonic development and in the adult brain. The pathological function of amyloid-β peptide has been extensively studied due to its implication in Alzheimer’s disease, but its physiological function remains poorly understood. Amyloid-β peptide can be detected in non-aggregated (monomeric) and aggregated (oligomeric and fibrillary) forms. Each form has different cytotoxic and/or physiological properties, so amyloid-β peptide and its role in Alzheimer’s disease need to be studied further. neural stem cells and neural precursor cells are good tools for the study on neurodegenerative diseases and can provide future therapeutic applications in diseases such as Alzheimer’s disease. In this review, we provide an outline of the effects of amyloid-β peptide, in monomeric and aggregated forms, on the biology of neural stem cells/neural precursor cells, and discuss the controversies. We also describe the possible molecular targets that could be implicated in these effects, especially GSK3β. A better understanding of amyloid-β peptide (both physiological and pathological), and the signaling pathways involved are essential to advance the field of Alzheimer’s disease.

关键词： amyloid-β peptide Aβ neural stem cells neural progenitor cells Alzheimer's disease amyloid precursor protein toxicity neurogenesis gliogenesis GSK3β

Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism

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World Journal of Gastroenterology 2017年第28期23卷 5246-5252页

作者： Fernando Díaz-Fontenla marta Castillo-Pradillo Arantxa Díaz-Gómez Luis Ibanez-Samaniego Pilar Gancedo Juan Adan Guzmán-de-Villoria Pilar Fernández-García Rafael Banares-Canizares Rita García-martínez unidad de Hepatología Servicio de Aparato DigestivoHospital General Universitario Gregorio Maranón Instituto de investigación Sanitaria Hospital Gregorio maranón Servicio de Aparato Digestivo Hospital Santa Bárbara Servicio de Radiodiagnóstico Hospital General Universitario Gregorio Maranón Centro de investigación Biomédica en Red de Salud mental Centro de investigación Biomédica en Red de enfermedades Hepáticas y Digestivas Facultad de medicina Universidad San Pablo CEU

Hepatic encephalopathy(HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events(i.e.,portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here,we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment,hyperammonaemia,electroencephalograph alterations,impaired neuropsychological performance,and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE,paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.

关键词： Hepatic encephalopathy Hypothyroidism Cognitive impairment Cirrhosis Portosystemic shunt magnetic resonance spectroscopy

Insulinoma after sleeve gastrectomy:A case report

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World Journal of Clinical Cases 2022年第18期10卷 6227-6233页

作者： miry Lobaton-Ginsberg Pilar Sotelo-González Claudia Ramirez-Renteria Fany Gabriela Juárez-Aguilar Aldo Ferreira-Hermosillo Facultad de medicina Universidad Anáhuac México NorteMexico City 52786Mexico Servicio de endocrinología Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSMexico City 06720Mexico unidad de investigación médica en enfermedades endocrinas Instituto Mexicano del Seguro SocialMexico City 06720Mexico Servicio de Anatomía Patológica Hospital de Especialidades del Centro Médico Nacional Siglo XXIIMSSMexico City 06720Mexico

BACKGROUnD Laparoscopic sleeve gastrectomy(LSG)has been proposed as an effective and durable treatment for severe obesity and glucose metabolism disorders,and its prevalence has increased from 5%to 37%since *** common complication after bariatric surgery is a postprandial hyperinsulinemic hypoglycemic *** rare,insulinomas can cause this state,where symptoms are more common in the fasting state;thus,evaluation of insulin secretion is *** now,there have been no reports of insulinoma after *** SUmmARY We describe the case of a 43-year-old woman who was referred to the obesity clinic 2 years after LSG was *** had symptoms of hypoglycemia predominantly in the fasting state and documented hypoglycemia of less than 30 mg/d L,which are compatible with Whipple’s ***,dumping syndrome was suspected,but after a second low fasting plasma glucose was documented,a 72-h fasting test was performed that tested *** tomography and endoscopic ultrasound were performed,identifying the presence of a homogeneous hypoechoic semioval tumoral lesion in the *** diagnosis was compatible with *** laparoscopic enucleation of the insulinoma,the symptoms and hypoglycemia *** histopathological report described a well-differentiated grade 2 neuroendocrine tumor with positive chromogranin and synaptophysin and Ki67 immunopositivity in 4%of the neoplastic *** Insulinoma after LSG is a rare condition,and clinicians must be aware of it,especially if the patient has hypoglycemic symptoms during the fasting state.

关键词： Insulinoma Hypoglycemia Bariatric surgery Glucagon-like peptide 1 amide neuroendocrine tumors Case report

Physiopathology of ischemic stroke and its modulation using memantine:evidence from preclinical stroke

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neural Regeneration Research 2021年第3期16卷 433-439页

作者： Hilda martínez-Coria Isabel Arrieta-Cruz maría-Esther Cruz Héctor E.López-Valdés División de investigación Facultad de MedicinaUniversidad Nacional Autónoma de México(UNAM)Ciudad de MéxicoMéxico Laboratorio Experimental de enfermedades neurodegenerativas Facultad de MedicinaUNAM/Instituto Nacional de Neurología y NeurocirugíaCiudad de MéxicoMéxico departamento de investigación Básica Instituto Nacional de GeriatríaCiudad de MéxicoMéxico unidad de investigación en Biología de la Reproducción Laboratorio de NeuroendocrinologíaFacultad de Estudios Superiores ZaragozaUNAMCiudad de MéxicoMéxico unidad Periférica de neurociencia Facultad de MedicinaUNAM/Instituto Nacional de Neurología y NeurocirugíaCiudad de MéxicoMéxico

Ischemic stroke is the most common type of cerebrovascular disease and is caused by an interruption of blood flow in the *** this disease,two different damage areas are identifying:the lesion core,in which cells quickly die;and the penumbra(surrounding the lesion core),in which cells are functionally weakened but may recover and restore their *** currently approved treatments for ischemic stroke are the recombinant tissue plasminogen activator and endovascular thrombectomy,but they have a short therapeutic window(4.5 and 6 hours after stroke onset,respectively)and a low percentage of stroke patients actually receive these *** is an approved drug for the treatment of Alzheimer's *** is a noncompetitive,low affinity and use-dependent antagonist of n-methyl-D-aspartate glutamate *** has several advantages over developing a new drug to treat focal ischemic stroke,but the most important is that it has sufficient safe probes in preclinical models and humans,and if the preclinical studies provide more evidence about pharmacological actions in tissue protection and repair,this could help to increase the number of clinical *** present review summarizes the physiopathology of isquemic stroke and the pharmacological actions in neuroprotection and neuroplasticity of memantine in the post stroke stage of preclinical stroke models,to illustrate their potential to improve functional recovery in human patients.

关键词： focal ischemic stroke memantine neuroplasticity neuroprotection stroke therapy

Vigorous,but differential mononuclear cell response of cirrhotic patients to bacterial ligands

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World Journal of Gastroenterology 2011年第10期17卷 1317-1325页

作者： Varenka J Barbero-Becerra maría Concepción Gutiérrez-Ruiz Carmen maldonado-Bernal Félix I Téllez-Avila Roberto Alfaro-Lara Florencia Vargas-Vorácková department of Gastroenterology Instituto Nacional de Ciencias Médicasy Nutrición Salvador Zubirán Laboratorio de Fisiología Celular División de Ciencias de la Salud Universidad Autónoma Metropolitana-Iztapalapa unidad de investigación médica en enfermedades Infecciosasy Parasitarias Hospital de Pediatría unidad de investigación en enfermedades Oncológicas Hospital Infantil de México Federico Gómez

AIm： To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. mETHODS： Peripheral blood mononuclear cells of 20 out-patients were studied, 10 of them with cirrhosis,Peripheral blood mononuclear cells were isolated and exposed to lipopolysaccharide or lipoteichoic acid. CD14, Toll-like receptor 2 and 4 expression was determined by flow cytometry, and tumor necrosis factor （TnF） α, interleukin （1L）-1β, IL-6, IL-12 and IL-10 secretion in su- pernatants was determined by ELISA. RESULTS： Higher CD14, Toll-like receptor 2 and 4 expression was observed in peripheral blood mononudear cells from cirrhotic patients, （P 〈 0.01, P 〈 0.006, P 〈 0.111） respectively. Lipopolysaccharide and lipoteichoic acid induced a further increase in CD14 expression （P 〈 0.111 lipopolysaccharide, P 〈 0.013 lipoteichoic acid）, and a decrease in Toll-like receptor 2 （P 〈 0.008 lipopolysaccharide, P 〈 0.008 lipoteichoic acid） and Toll-like receptor 4 （P 〈 0.008 lipopolysaccharide, P 〈 0.028 li- poteichoic acid） expression. With the exception of TnFα, absolute cytokine secretion of peripheral blood mononuclear cells was lower in cirrhotic patients under nonexposure conditions （P 〈 0.070 IL-6, P 〈 0.009 IL-1]5, P 〈 0.022 IL-12）. Once exposed to lipopolysaccharide or lipoteichoic acid, absolute cytokine secretion of peripheral blood mononuclear cells was similar in cirrhotic and non-cirrhotic patients, determining a more vigorous response in the former （P 〈 0.005 TnFα, IL-1β, IL-6, IL-2 and IL-10 lipopolysaccharide; P 〈 0.037 TnFα; P 〈 0.006 IL-113; P 〈 0.005 IL-6; P 〈 0.007 IL-12; P 〈 0.014 IL-10 lipoteichoic acid）. Response of peripheral blood mononuclear cells was more intense after lipopolysaccharide than after lipoteichoic acid exposure. COnCLUSIOn： Peripheral blood mononuclear cells of cirrhotic patients are able to respond to a sudden bacterial ligand exposure, particularly lipopolysaccharide, sugg

关键词： Liver cirrhosis Toll-like receptors Cytokines Lipopolysaccharide Lipoteichoic acid

Expression of triggering receptor on myeloid cell 1 and histocompatibility complex molecules in sepsis and major abdominal surgery

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World Journal of Gastroenterology 2005年第47期11卷 7473-7479页

作者： nestor González-Roldán Eduardo Ferat-Osorio Rosalía Aduna-Vicente Isabel Wong-Baeza noemí Esquivel-Callejas Horacio Astudillo-de la Vega Patricio Sánchez-Fernández Lourdes Arriaga-Pizano miguel Angel Villasís-Keever Constantino López-macías Armando Isibasi unidad de investigación médica en Inmunoquímica Hospital de EspecialidadesCentro Médico Nacional Siglo ⅩⅪInstituto Mexicano del Seguro Social (IMSS)México Laboratorio de Oncología molecular Unidad de Investigación Médica en Enfermedades OncológicasHospital de OncologíaCentro Médico Nacional Siglo ⅩⅪIMSSMéxico Servicio de Gastrocirugía Hospital de EspecialidadesCentro Médico Nacional Siglo ⅩⅪIMSSMéxico unidad de investigación en Epidemiología Clínica Hospital de PediatríaCentro Médico Nacional Siglo ⅩⅪIMSSMéxico

AIm： To evaluate the surface expression of triggering receptor on myeloid cell 1 （TREm-1）, class Ⅱ major histocompatibility complex molecules （HLA-DR）, and the expression of the splicing variant （svTREH-1） of TREm-1 in septic patients and those subjected to major abdominal surgery. mETHODS： Using flow cytometry, we examined the surface expression of TREm-1 and HLA-DR in peripheral blood monocytes from 11 septic patients, 7 elective gastrointestinal surgical patients, and 10 healthy volunteers, svTREm-1 levels were analyzed by RT-PCR. RESULTS： Basal expression of TREm-1 and HLA- DR in healthy volunteers was 35.91±14.75 mFI and 75.8±18.3%, respectively. In septic patients, TREm-1 expression was 59.9±23.9 mFI and HLA-DR expression was 44.39±20.25%, with a significant difference between healthy and septic groups （P〈0.05） for both molecules. In the surgical patients, TREm-1 and HLA-DR expressions were 56.8±20.85 HFI and 71±13.8% before surgery and 72.65±29.92 mFI and 72.82±22.55% after surgery. TREm-1 expression was significantly different （P = 0.0087） between the samples before and after surgery and svTREm-1 expression was 0.8590± 0.1451 mF1, 0.8820±0.1460 mF1, and 2.210±0.7873 mF1 in the healthy, surgical （after surgery） and septic groups, respectively. There was a significant difference （P = 0.048） in svTREm-1 expression between the healthy and surgical groups and the septic group. COnCLUSIOn： TREm-1 expression is increased during systemic inflammatory conditions such as sepsis and the postoperative phase. Simultaneous low expression of HLA-DR molecules correlates with the severity of illness and increases susceptibility to infection. Additionally, TREm-1 expression is distinctly different in surgical patients at different stages of the inflammatory response before and after surgery. Thus, surface TREm-1 appears to be an endogenous signal during the course of the inflammatory response, svTREm-1 expression is significantly increased during sepsis, appearing to be a

关键词： TRFm-1 HLA-DR SIRS CARS Sepsis

Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone

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neural Regeneration Research 2018年第3期13卷 440-448页

作者： Rodolfo Pinto-Almazán Julia J. Segura-Uribe marvin A. Soriano-Ursúa Eunice D. Farfán-García Juan m. Gallardo Christian Guerra-Araiza unidad de investigación Hospital Regional de Alta Especialidad Ixtapaluca Carretera Federal México-Puebla km 34.5 C.P. 56530. Ixtapaluca State of Mexico Mexico Institute for the developing mind Children's Hospital Los Angeles Los Angeles CA USA department of Pediatrics Keck School of Medicine University of Southern California Los Angeles CA USA unidad de investigación médica en enfermedades neurológicas Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Av. Cuauhtémoc 330 Col. Doctores. C. P. 06720. Mexico City Mexico Escuela Superior de medicina Instituto Politécnico Nacional Plan de San Luis y Diaz Mirón Col. Casco de Santo Tomis. C. P. 11340. Mexico City Mexico unidad de investigación médica en enfermedades nefrológicas Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Av. Cuauhtémoc 330 Col. Doctores. C. P. 06720. Mexico City Mexico unidad de investigación médica en Farmacologia Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Av. Cuauhtémoc 330 Col. Doctores. C. P. 06720. Mexico City Mexico

Oxidative stress （OS） is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone （TIB）, a synthetic hormone used as a treatment for menopausal ymptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone （O3） exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β （GSK3β）, and the inactivation of Akt and phosphatases PP2A and PTen induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups： control group （ozone-free air plus vehicle [C]）, control ＋ TIB group （ozone-free air plus TIB 1 mg/kg [C ＋ TIB]）; 7,15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 ＋ TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTen proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods （marklund and TBARS, respectively）. We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTen protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment （over 15 days） with TIB. malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results

关键词： tibolone oxidative stress ozone exposure Tau GSK3 hippocampus neuroprotection

What can we learn from β-cell failure biomarker application in diabetes in childhood?A systematic review

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World Journal of Diabetes 2021年第8期12卷 1325-1362页

作者： maría F Calderón-Hernández nelly F Altamirano-Bustamante Cristina Revilla-monsalve maría Belen mosquera-Andrade myriam m Altamirano-Bustamante unidad de investigación en enfermedades metabólicas Centro Médico Nacional Siglo XXIIMSSMexico 06720Mexico department of endocrinology Instituto Nacional de PediatríaMexico 04530Mexico

BACKGROUnD The prevalence of diabetes as a catastrophic disease in childhood is growing in the *** search for novel biomarkers ofβ-cell failure has been an elusive task because it requires several clinical and biochemical measurements in order to integrate the risk of metabolic *** To determine which biomarkers are currently used to identifyβ-cell failure among children and adolescents with high risk factors for diabetes *** This systematic review was carried out using a modified version of the PICO protocol(Participants/Intervention/Comparison/Outcome).Once our research question was established,terms were individually researched on three different databases(Pubmed,BIREmE and Web of Science).The total articles obtained underwent a selection process from which the 78 most relevant articles were retrieved to undergo further *** were assessed individually according to quality *** First,we made the classification of theβ-cell-failure biomarkers by the target tissue and the evolution of the disease,separating the biomarkers in relation to the types of ***,we demonstrated that most biomarkers currently used as early signs ofβ-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction ***,we explored the novelties of diabetes as a protein conformational disease and the novel biomarker called real human islet amyloid polypeptide amyloid ***,we ended with a discussion about the best practice of validation and individual control of using different types of biomarkers in type 1 and type 2 diabetes in order to assess the role they play in the progress of diabetes in *** This review makes widely evident that most biomarkers currently used as early signs ofβ-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endo

关键词： Biomarker β-cell failure Children Adolescents Diabetes mellitus metabolic syndrome