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

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

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The complex role of protocadherin-19 in brain function:a focus on the oxytocin system

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Neural Regeneration Research 2025年第11期20卷 3211-3212页

作者： Sara Mazzoleni marta Busnelli Silvia Bassani CNR Institute of Neuroscience Vedano al LambroItaly NeuroMi Milan Center for Neuroscience MilanItaly

Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive *** seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).

关键词： epilepsy function system

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-Mañé Laia Just-Borràs marta Balanyà-Segura Aleksandra Polishchuk Laura Nadal marta Tomàs Carolina Silvera-Simón Manel M.Santafé Maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

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Neural Regeneration Research 2025年第10期20卷 2872-2886页

作者： marta Chierichetti Riccardo Cristofani Valeria Crippa Veronica Ferrari marta Cozzi Elena Casarotto Paola Pramaggiore Laura Cornaggia Guglielmo Patelli Ali Mohamed Margherita Piccolella Mariarita Galbiati Paola Rusmini Barbara Tedesco Angelo Poletti Laboratory of Experimental Biology Dipartimento di Scienze Farmacologiche e Biomolecolari“Rodolfo Paoletti”(DiSFeB)Universitàdegli Studi di MilanoMilanItaly

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock ***8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and ***8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective *** line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and *** cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under ***,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar *** note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other *** is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial *** review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its ***-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

关键词： aggregation autophagy cancer chaperone chaperone-assisted selective autophagy cognitive impairment HSPB8 neuroinflammation neuromuscular diseases therapy

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Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： marta García-Juan Mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

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Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

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Not only myelination: the immune-inflammatory functions of oligodendrocytes

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Neural Regeneration Research 2022年第12期17卷 2661-2663页

作者： marta Boccazzi Stefano Raffaele marta Fumagalli Department of Pharmacological and Biomolecular Sciences Universitàdegli Studi di MilanoMilanItaly

Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulation and the saltatory conduction of nerve *** formation of myelin is a complex process during which the OL precursor cells(OPCs,also known as NG2-glia)become mature OLs through a highly regulated program of *** addition,OPCs persist in the adult grey and white matter parenchyma,representing approximately 6%of the total number of CNS *** their role in myelin generation and turn-over,it is now clear that OPCs have the capability to control tissue homeostasis and to sense and react to inflammation which characterizes many neurological diseases.

关键词： myelin cytes homeostasis

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Evolution of temperature indices in the periglacial environment of the European Alps in the period 1990-2019

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Journal of Mountain Science 2021年第11期18卷 2842-2853页

作者： NIGRELLI Guido CHIARLE marta National Research Council Research Institute for Geo-hydrological ProtectionStrada delle Cacce73–TorinoItaly

Air temperature in the European Alps shows warming over recent decades at an average rate of 0.3℃/10 years,therebyoutpacing the global warming rate of 0.2℃/10 *** periglacial environment of the Alps is particularly important for several aspects(*** production,tourism,natural hazards,indicator of global warming).However,there is a lack of specific and updated studies relating to temperature change in this *** order to fill this gap,the recent temperature trends in the periglacial environment of the Alps were ***/maximum/minimum daily air temperatures recorded by 14 land-based meteorological stations were used,and the temperature indices for the period 1990-2019 were *** periglacial environment of the Alps showed a warming rate of 0.4℃/10 years,0.6℃/10 years and 0.8℃/10 years for the mean/maximum/minimum temperatures,*** warming rates are higher than that observed for the entire Alpine *** 2050 many glaciers of the Alps below 3000 m altitude are expected to be extinct,and all the areas previously occupied by glaciers will become *** order to manage and adapt to these changes,more in-depth climate analyses are *** is necessary for all the mountainous areas of the world,which are undergoing similar changes.

关键词： Mountain climate Cryosphere Climate change Extreme temperature Air temperature trend

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1991-2020 climate normal in the European Alps:focus on high-elevation environments

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Journal of Mountain Science 2023年第8期20卷 2149-2163页

作者： NIGRELLI Guido CHIARLE marta Istituto di Ricerca per la Protezione Idrogeologica Consiglio Nazionale delle RicercheTorino 10135Italy

Alps are an important geographical area of the European continent and,in this area,temperature increase is most ***,the 1991-2020 climate normal in the Alps has still not been thoroughly *** to fill this gap with a focus on high-elevation environments,minimum and maximum daily air temperature acquired by 23 automatic weather station were *** results show that the mean annual values of minimum and maximum temperature for the 1991-2020 climate normal in the Alps are-2.4℃ and 4.4℃,respectively,with a warming rate of 0.5℃/10 *** mean annual temperature comparison between 1961-1990 and 1971-2000,1961-1990 and 1981-2010,1961-1990 and 1991-2020 climate normal show an increase of 0.3℃,0.5℃ and 0.9℃,*** results also confirm that seasonal and annual temperatures are rising through the whole Alpine arc,mainly in summer and *** work highlights that annual minimum and maximum temperature do not seem to be affected by a positive elevation-dependent ***,a positive elevation-dependent warming in the maximum values of the annual minimum temperature was *** anthropogenic emissions maintain the trend of the last decades,the expected mean annual temperature of the 2001-2030 climate normal is-0.2℃,with an increase of 0.5℃ if compared to the 1991-2020 climate normal and with an increase of 1.5℃ if compared to the 1961-1990 climate *** study highlights the warming rate that is now present in the European Alps,provides indications on the warming rate that will occur in the coming years and highlights the importance of carrying out investigations that consider not only the last 30-year climate normal,but also the most recent 30-year climate normal by comparing them with each other.

关键词： Air temperature trend Climate normal Climate change High mountain climate Alps

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How useful are biomarkers for the diagnosis of Alzheimer’s disease and especially for its therapy?

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Neural Regeneration Research 2022年第10期17卷 2205-2207页

作者： marta Valenza Caterina Scuderi Department of Physiology and Pharmacology“V.Erspamer” SAPIENZA University of RomeRomeItaly

Alzheimer’s disease key facts:Alzheimer’s disease(AD)is a slowly progressive neurodegenerative disease with no available effective *** is possible to distinguish an early-onset AD that affects a limited number of subjects of young age,and a sporadic or late-onset form of the disease that affects the vast majority of subjects who are diagnosed with *** life expectancy has increased considerably over the past century,the number of people diagnosed with AD has grown ***,AD and AD-related pathologies represent a huge social and economic *** number of individuals waiting for effective disease-modifying therapy is *** is estimated that 50 million people worldwide live with dementia,the majority of these cases are caused by AD(World Health Organization,2021).In the US about 6 million individuals are living with AD,and more than 9 million people are in EU member states(OECD and European Union,2020).The costs of health care and long-term care are *** this massive societal impact,enormous efforts have been made to understand the pathogenetic mechanisms of the disease with the hope of identifying new targets and,therefore,developing effective drugs.

关键词： Alzheimer diagnosis slowly

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