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Thinking outside the black box:are the brain endothelial cells the new main target in Alzheimer's disease?

Neural Regeneration Research 2023年第12期18卷 2592-2598页

作者： Enrique Estudillo Adolfo López-Ornelas Alejandro Rodríguez-Oviedo Neptali Gutiérrez de la Cruz Marco Antonio Vargas-Hernández Adriana Jiménez Laboratorio de Reprogramación Celular Instituto Nacional de Neurología y Neurocirugía Manuel Velasco SuárezMexico CityMexico División de Investigación Hospital Juárez de MéxicoMexico CityMexico Hospital Nacional Homeopático Hospitales Federales de ReferenciaMexico CityMexico Facultad de Ciencias Universidad Nacional Autónoma de MéxicoMexico CityMexico Laboratorio de Morfología Escuela Militar de Graduados de SanidadSecretaría de la Defensa NacionalBatalla de CelayaLomas de SoteloMiguel HidalgoMexico CityMexico Escuela Militar de Graduados de Sanidad Secretaría de la Defensa NacionalBatalla de CelayaLomas de SoteloMiguel HidalgoMexico CityMexico

The blood-brain barrier is the interface through which the brain interacts with the milieu and consists mainly of a sophisticated network of brain endothelial cells that forms blood vessels and selectively moves molecules inside and outside the brain through multiple mechanisms of transport.Although brain endothelial cell function is crucial for brain homeostasis,their role in neurodegenerative diseases has historically not been considered with the same importance as other brain cells such as microglia,astroglia,neurons,or even molecules such as amyloid beta,Tau,or alpha-synuclein.Alzheimer's disease is the most common neurodegenerative disease,and brain endothelial cell dysfunction has been reported by several groups.However,its impairment has barely been considered as a potential therapeutic target.Here we review the most recent advances in the relationship between Alzheimer's disease and brain endothelial cells commitment and analyze the possible mechanisms through which their alterations contribute to this neurodegenerative disease,highlighting their inflammatory phenotype and the possibility of an impaired secretory pattern of brain endothelial cells that could contribute to the progression of this ailment.Finally,we discuss why shall brain endothelial cells be appreciated as a therapeutic target instead of solely an obstacle for delivering treatments to the injured brain in Alzheimer's disease.

关键词： dementia endothelial cells neurodegeneration neuroinflammation neuronal death paracellular transport transcellular transport

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New insights into Wnt signaling alterations in amyotrophic lateral sclerosis: a potential therapeutic target?

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Neural Regeneration Research 2020年第9期15卷 1580-1589页

作者： Carlos González-Fernández Pau González Francisco Javier Rodríguez Laboratory of Molecular Neurology Hospital Nacional de Parapléjicos (HNP)

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by upper and lower motor neuron degeneration, which leads to progressive paralysis of skeletal muscles and, ultimately, respiratory failure between 2–5 years after symptom onset. Unfortunately, currently accepted treatments for amyotrophic lateral sclerosis are extremely scarce and only provide modest benefit. As a consequence, a great effort is being done by the scientific community in order to achieve a better understanding of the different molecular and cellular processes that influence the progression and/or outcome of this neuropathological condition and, therefore, unravel new potential targets for therapeutic intervention. Interestingly, a growing number of experimental evidences have recently shown that, besides its well-known physiological roles in the developing and adult central nervous system, the Wnt family of proteins is involved in different neuropathologica conditions, including amyotrophic lateral sclerosis. These proteins are able to modulate, at least, three different signaling pathways, usually known as canonical(β-catenin dependent) and non-canonical(β-catenin independent) signaling pathways. In the present review, we aim to provide a general overview of the current knowledge that supports the relationship between the Wnt family of proteins and its associated signaling pathways and amyotrophic lateral sclerosis pathology, as well as their possible mechanisms of action. Altogether, the currently available knowledge suggests that Wnt signaling modulation might be a promising therapeutic approach to ameliorate the histopathological and functional deficits associated to amyotrophic lateral sclerosis, and thus improve the progression and outcome of this neuropathology.

关键词： ALS astrocytes Frizzled human microglia motor neuron neurodegeneration neuroinflammation spinal cord Wnt

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Tips and tricks for cannabinoid receptor 1 detection, interaction and interpretation

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Neural Regeneration Research 2021年第8期16卷 1535-1536页

作者： Pedro F.Esteban Eduardo Molina-Holgado Laboratory of Neuroinflammation Hospital Nacional de Parapléjicos(SESCAM)ToledoSpain

Proteomic approaches are currently used to explore and identify interacting partners of proteins involved in diverse biological processes or with therapeutic potential.The cannabinoid receptor 1,CB_1,is the main mediator of cannabinoids effects in the central nervous system.The role of the endocannabinoid system in development and physiology and as a target of pharmacological and cellular therapies is the subject of intense research.Therefore。

关键词： potential. interaction intense

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A comprehensive review of genetic causes of obesity

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World Journal of Pediatrics 2024年第1期20卷 26-39页

作者： Marcio Jose Concepcion-Zavaleta Juan Eduardo Quiroz-Aldave Maria del Carmen Durand-Vasquez Elman Rolando Gamarra-Osorio Juan del Carmen Valencia de la Cruz Claudia Mercedes Barrueto-Callirgos Susan Luciana Puelles-Leon Elena de Jesus Alvarado-Leon Frans Leiva-Cabrera Francisca Elena Zavaleta-Gutierrez Luis Alberto Concepcion-Urteaga Jose Paz-Ibarra Universidad Cientifica del Sur Bolivar 2150 AvenuePueblo Libre15084LimaPeru Division of Medicine Hospital de Apoyo ChepénChepenPeru Division of Family Medicine Hospital de Apoyo ChepénChepenPeru Division of Endocrinology Hospital Victor Lazarte EchegarayTrujilloPeru Division of Pediatrics Hospital de Apoyo ChepenChepenPeru Division of Internal Medicine Hospital de Apoyo ChepenChepenPeru Division of Genetics Universidad Nacional de TrujilloTrujilloPeru Division of Neonatology Hospital Belen de TrujilloTrujilloPeru Division of Internal Medicine Universidad Nacional de TrujilloTrujilloPeru Department of Medicine School of MedicineUniversidad Nacional Mayor de San MarcosLimaPeru

Background Obesity is a multifactorial chronic disease with a high,increasing worldwide prevalence.Genetic causes account for 7%of the cases in children with extreme obesity.Data sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 articles.The search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case reports.Results The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight.However,several important aspects of the pathophysiology of obesity remain unknown.Genetic causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose.There are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric surgery.Conclusions Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.

关键词： Leptin Melanocortin Obesity Prader-Willi syndrome Precision medicine

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All roads go to Salubrinal:endoplasmic reticulum stress,neuroprotection and glial scar formation

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Neural Regeneration Research 2015年第12期10卷 1926-1927页

作者： Lorenzo Romero-Ramírez Manuel Nieto-Sampedro M.Asunción Barreda-Manso hospital nacional de Parapléjicos SESCAM Instituto Cajal CSIC

Central nervous system（CNS）injuries caused by cerebrovascular pathologies（e.g.,stroke）or mechanical contusions（e.g.,traumatic brain injury）disrupt the blood-brain barrier（BBB）that protects the CNS microenviron... 详细信息

关键词： ER CNS TGF

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Auditory function in symptomatic patients recovered from SARS-CoV-2 and unexposed patients:An analytical cross-sectional study

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Journal of Otology 2023年第3期18卷 118-124页

作者： Katherin Andrea Borda Pedraza Sergio Mauricio Moreno Lopez Javier Amaya-Nieto Liliana Akli Serpa Ginna Paola Saavedra Martínez Mauricio Ernesto Quinche Pardo Alberto Pena Valenzuela Otorhinolaryngology Department Universidad Nacional ColombiaColombia Epidemiology Department Universidad de Los AndesColombia Health Systems and Services Research Group Universidad Nacional de ColombiaBogotaColombia Audiology Department Universidad Nacional de ColombiaColombia Health and Social Protection Ministry Colombia Universidad nacional Colombia Colombia Otorhinolaryngology Department Universidad Nacional de ColombiaColombia

Objective:To describe audiological symptoms,audiometric profile,and distortion product otoacoustic emission in symptomatic patients recovering from SARS-CoV-2 infection(positive RT-PCR test)and asymptomatic patients(negative RT-PCR test).Methods:An analytical cross-sectional study was conducted using data obtained from clinical charts,physical examination,audiometry,and distortion product otoacoustic emission on 40 patients[case patients(CP)]recovering from SARS-CoV-2 infection diagnosed by a positive RT-PCR test and 22asymptomatic participants with a negative RT-PCR test[non-case(NC)].Results:Sixty-two patients(mean age:31.1 and 28.2 years in the CP and NC groups,respectively)were included.All participants were young without significant comorbidities,risk factors for hearing loss or otological history.Vertigo(5%),tinnitus(17.5%)and aural fullness/hearing loss(35%)were found in the CP group.A statistically significant difference was found in specific frequencies(1000,4000,and 8000 Hz)and pure tone average(low and high conversational frequencies with increased threshold in the PC group compared with the NC group),which was not found in distortion product otoacoustic emission.Conclusion:Audiovestibular symptoms are frequent in symptomatic patients recovering from SARS-CoV-2 infection.SARS-CoV-2 infection was consistently associated with an increased audiometric hearing threshold at specific frequencies and low tone average.

关键词： SARS-CoV-2 Cochlear diseases Pure tone audiometry Otoacoustic emissions Hearing loss Otological symptoms

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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-Pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero hospital nacional de Parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

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Tauroursodeoxycholic acid:more than just a neuroprotective bile conjugate

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Neural Regeneration Research 2017年第1期12卷 62-63页

作者： Lorenzo Romero-Ramírez Manuel Nieto-Sampedro Natalia Yanguas-Casás hospital nacional de Paraplejicos SESCAMToledoSpain Instituto Cajal CSICMadridSpain

Neurological diseases and the neuroinflammatory response：Neurological diseases are usually accompanied by dramatic changes in the tissue homeostasis,inducing a neuroinflammatory environment that leads to the progress... 详细信息

关键词： Tauroursodeoxycholic acid more than just a neuroprotective bile conjugate TGF CNS

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Autoimmune hepatitis in human immunodeficiency virus infection: Case report and literature review

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World Journal of Clinical Infectious Diseases 2017年第4期7卷 50-57页

作者： Ivan Nore?a Jairo A Morantes-Caballero Andrés Garcés Brian José Gómez Gabriel Rodríguez Carlos Saavedra William Otero Infectious Diseases Section Department of Internal Medicine Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia Department of Internal Medicine Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia Gastroenterology Section Department of Internal Medicine Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia

The infection due to human immunodeficiency virus(HIV) is characterized by the progressive reduction of CD4+ T lymphocytes and the compromise of other cell lines of the immune system, resulting in immunosuppression. In this context, autoimmune diseases could be considered contradictory, however, cases of autoimmune diseases during this infection have been described, including autoimmune hepatitis(AIH), which is uncommon and has few case reports within medical literature, none of them from Latin America. In this case report where a patient with an HIV infection on combined antiretroviral treatment developed acute elevation of transaminases, hyperbilirubinemia, and deterioration in hepatic synthetic function. Although initially an antiretroviral drug-induced liver injury was suspected, during the study a diagnosis of autoimmune hepatitis was proven, which required treatment with corticosteroid and azathioprine, obtaining a satisfactory response and managing to continue the antiretroviral therapy. Autoimmune diseases in HIV infection must be taken into account. In the case of hepatitis in patients with HIV on antiretroviral treatment, the differentiation between viral hepatitis caused by autoimmune diseases or medications is essential to establish an adequate treatment, and avoid the suspension of the antiretroviral therapy.

关键词： Autoimmunity Autoimmune hepatitis Human immunodeficiency virus Anti-human immunodeficiency virus agents Drug-induced liver injury

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Is retinoic acid a signal for nerve regeneration in insects?

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Neural Regeneration Research 2015年第6期10卷 901-903页

作者： Katrin Bui-Gobbels Renata Medinaceli Quintela Peter Braunig Jorg Mey Institut für Biologie II RWTH Aachen University hospital nacional de Parapléjicos Euron Graduate School of Neuroscience

Until quite recently the retinoic acid （RA） signaling pathway was believed to occur only in vertebrates, but in the last decade, several ground-breaking studies have shown that it also exists in invertebrates. These include the discovery of endogenous retinoids （Nowickyj et al., 2008）, of retinoid receptor orthologs in insects （Hayward et al., 1999） and the very specific effect of RA on axonal guidance in the fresh water snail Lymnaea stagnalis （Dmetrichuk et al., 2008）. Despite some earlier indications of RA-dependent gene activation in insects, these papers really started retinoid research in invertebrates.

关键词：化学临床/仪器和设备昆虫内皮缩血管肽类神经再生维甲酸维生素A酸类无脊椎动物胰岛素

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