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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte roc.. Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

Kidney transplantation outcomes: Is it possible to improve when good results are falling down?

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World Journal of Transplantation 2024年第3期14卷 1-4页

作者： Fernando M Gonzalez Francisca del roc.. Gonzalez Cohens Department of Nephrology Faculty of MedicineUniversidad de ChileSantiago 7500922Chile Web Intelligence Centre Faculty of Physics and Mathematical SciencesUniversidad de ChileSantiago 8370397Chile

Famure et al describe that close to 50%of their patients needed early or very early hospital readmissions after their kidney *** they taught us the variables related to those outcomes,we describe eight teaching capsules that may go beyond what they describe in their *** two capsules talk about the ideal donors and recipients we should choose for avoiding the risk of an early *** third and fourth capsules tell us about the reality of cadaveric donors and recipients with comorbidities,and the way transplant physicians should choose them to maximize *** capsule shows that any mistake can result in an early readmission,and thus,in poorer *** capsule talks about economic losses of early readmissions,cost-effectiveness of tran-splantation,and how to improve outcomes and reduce costs by managing a risky *** capsule argues about knowing your risk behavior to better manage your portfolio;and Eighth capsule about the importance of the center experience in transplanting complex *** finish with some lessons of the importance of the transplantation proc..s and the collaboration with other disciplines in order to prevent the conditions that lead to early readmissions.

关键词： Kidney tranplantation Hospitalization prognostic factors portfolio theory Transplant

Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration

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Neural Regeneration Research 2023年第6期18卷 1196-1202页

作者： Instituto de Salud Carlos III Irene Villalón-García Suleva povea-Cabello MónicaÁlvarez-Córdoba Marta Talaverón-Rey Juan MSuárez-Rivero Alejandra Suárez-Carrillo Manuel Munuera-Cabeza Diana Reche-López paula Cilleros-Holgado roc.. piñero-pérez JoséA.Sánchez-Alcázar Centro Andaluz de Biología del Desarrollo(CABD-CSIC-Universidad pablo de Olavide de Sevilla) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos IIISevillaSpain

Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation *** dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these ***,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration proc..ses is *** this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular *** vicious cycle established between both pathological alterations may lead to the development of ***,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict *** addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in pLA2G6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.

关键词： 4-hidroxynonenal ferroptosis iron lipid peroxidation lipofuscin neurodegeneration neurodegeneration with brain iron accumulation oxidative stress pLA2G6-associated neurodegeneration

Management of recurrent hepatitis C virus after liver transplantation

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World Journal of Gastroenterology 2014年第44期20卷 16409-16417页

作者： Miguel Jiménez-pérez roc.. González-Grande Francisco Javier Rando-Mu?oz Liver transplantation and hepatology unit UGC de Aparato Digestivo Hospital Regional Universitario Department of Abdominal Diseases Hospital Nij Smellinghe Ziekenhuis

Chronic hepatitis C virus (HCV) infection is the leading cause of death from liver disease and the leading indication for liver transplantation (LT) in the United States and Western Europe. LT represents the best therapeutic alternative for patients with advanced chronic liver disease caused by HCV or those who develop hepatocarcinoma. Reinfection by HCV of the graft is universal and occurs in 95% of transplant patients. This reinfection can compromise graft function and patient survival. In a few cases, the histological recurrence is minimal and non-progressive; however, in most patients it follows a more rapid course than in immunocompetent persons, and frequently evolves into cirrhosis with graft loss. In fact, the five-year and ten-year survival of patients transplanted because of HCV are 75% and 68%, respectively, compared with 85% and 78% in patients transplanted for other reasons. There is also a pattern of recurrence that is very severe, but rare (patitis, which often involves rapid graft loss. patients who present a negative HCV viremia after antiviral treatment have better survival. Many studies published over recent years have shown that antiviral treatment of post-transplant HCV hepatitis carried out during the late phase is the best option for improving the prognosis of these patients. Until 2011, pEGylated interferon plus ribavirin was the standard of care, resulting in a sustained virological response in around 30% of recipients. The addition of protease inhibitors, such as boceprevir or telaprevir, to the standard of care, or the use of other direct-acting antiviral drugs may involve therapeutic changes in the context of HCV recurrence. This may result a better prognosis for these patients, particularly those with severe recurrence or factors predicting rapid progression of fibrosis. However, the use of these agents in LT still requires clarification in terms of safety and efficacy.

关键词： Hepatitis C virus Liver transplantation Recurrence Treatment

Diabetic nephropathy,autophagy and proximal tubule protein endocytic transport:A potentially harmful relationship

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BIOCELL 2018年第2期42卷 35-40页

作者： Maximiliano GIRAUD-BILLOUD Claudio M.FADER roc.. AGÜero Fernando EZQUER Marcelo EZQUER IHEM Universidad Nacional de CuyoCONICETMendozaArgentina Universidad Nacional de Cuyo Facultad de Ciencias MédicasInstituto de FisiologíaCasilla de Correo 335500-MendozaArgentina Universidad Nacional de Cuyo Facultad de OdontologíaCasilla de Correo 335500-MendozaArgentina Centro de Medicina Regenerativa Facultad de Medicina Clínica AlemanaUniversidad del DesarrolloAvenida Las Condes 12438SantiagoChile

Diabetic nephropathy(DN)is the most frequent cause of chronic renal *** now,the pathophysiological mechanisms that determine its development and progression have not yet been *** the present study,we evaluate the role of autophagy at early stages of DN,induced in type 2 diabetes mellitus(T2DM)mouse,and its association with proximal tubule membrane endocytic receptors,megalin and *** T2DM animals we observed a tubule-interstitial injury with significantly increased levels of urinary GGT and ALp,but an absence of tubulointerstitial *** proximal tubule cells of T2DM animals showed autophagic vesicles larger than those observed in the control group,and an increase in the number of these vesicles marked with LBpA by ***,a significant decrease in the ratio of LC3II/LC3I isoforms and in p62 protein expression in DN affected animals is ***,we observed a marked increase in urinary albumin and vitamin D binding-protein levels in T2DM animals as well as a significant decrease in expression of megalin in the renal *** results indicate an alteration of the tubular endocytic transporters in DN,which could be related to autophagic dysfunction,which would in turn result in impaired organelle recycling,thus contributing to the progression of this disease.

关键词： Megalin Cubilin Type 2 diabetes mellitus

present and future management of viral hepatitis

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World Journal of Gastroenterology 2021年第47期27卷 8081-8102页

作者： roc.. González Grande Inmaculada Santaella Leiva Susana López Ortega Miguel Jiménez pérez UGC de Aparato Digestivo.Unidad de Hepatología-Trasplante Hepático Hospital Regional Universitario de MálagaMálaga 29010Spain

Viral hepatitis can result in important morbidity and mortality,with its impact on health conditioned by the specific type of hepatitis,the geographical region of presentation and the development and access to new drugs,among other *** acute presentation forms are self-limiting and may even go unnoticed,with just a small percentage of cases leading to acute liver failure that may necessitate transplantation or even cause the death of the ***,when they become chronic,as in the case of hepatitis B virus and C virus,unless they are diagnosed and treated adequately they may have severe consequences,like cirrhosis or *** of the mechanisms of transmission,the pathogenesis,the presence of vaccinations and the development over recent years of new highly-efficient,potent drugs have meant that we are now faced with a new scenario in the management of viral hepatitis,particularly hepatitis B virus and hepatitis C *** spectacular advances in hepatitis C virus treatment have led the World Health Organization to propose the objective of its eradication by *** key aspect to achieving this goal is to ensure that these treatments reach all the more vulnerable population groups,in whom the different types of viral hepatitis have a high prevalence and constitute a niche that may perpetuate infection and hinder its ***,microelimination programs assume special relevance at the present time.

关键词： Hepatitis viral Diagnosis Treatment Trend direct-acting antivirals Inhibiting recycling

Hidden diversity of marine borderline lichens and a new order of fungi:Collemopsidiales(Dothideomyceta)

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Fungal Diversity 2016年第5期80卷 285-300页

作者： Sergio pérez-Ortega Isaac Garrido-Benavent Martin Grube roc.. Olmo Asunción de los Ríos Museo Nacional de Ciencias Naturales(CSIC) Serrano 115 dpdoE-28006 MadridSpain Real Jardín Botánico de Madrid(CSIC) Plaza Murillo 2E-28014 MadridSpain Institute of plant Sciences University of GrazHolteigasse 6A-8010 GrazAustria Facultad de Ciencias Ambientales y Bioquímica Universidad de Castilla-La ManchaAvenida de Carlos III s/n45071 ToledoSpain

The fungal genus Collemopsidium comprises species that develop so-called borderline lichen symbioses with algae or *** with morphologically similar pyrenocarpous fungi it has been assigned to the family *** adscription of this family to higher taxonomic ranks remain *** sequence data of five nuclear genomic regions(nuLSU,nuSSU,tef1-α,rpb1 and rpb2)and onemitochondrial locus(mtSSU)we found that the studied representatives of this family are placed in the Dothideomyceta,yet relationships with the classes Dothideomycetes and Arthoniomycetes remain *** describe the new order Collemopsidiales to accommodate the genus Collemopsidium(paraphyletic as currently understood)and the lichenicolous genus *** five fungal fossils as calibrations points,we infer an age of c.230 Mya for the crown of *** on two molecular markers,we also provide insight into the global diversity of marine species of the genus *** to the species delimitation algorithm GMYC,c.26 putative species exist,far more than the six species recognized *** have confirmed this result by comparing the two alternative species models by means of Bayes factors,using path sampling and stepping-stone sampling algorithms to estimate the marginal likelihood of each ***,our observations suggest roc..boring ability evolved in parallel in the different lineages within this group of fungi.

关键词： Borderline lichens Dothideomycetes Endolithics.Lichen-forming fungi Lichenicolous fungi Boring ability Marine fungi Model comparison

Chronic pain, posttraumatic stress disorder, and opioid intake: A systematic review

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World Journal of Clinical Cases 2019年第24期7卷 4254-4269页

作者： Alicia E López-Martínez ángela Reyes-pérez Elena roc.. Serrano-Ibá?ez Rosa Esteve Carmen Ramírez-Maestre Facultad de psicología Instituto de Investigaciones Biomédicas (IBIMA)Universidad de Málaga

BACKGROUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(pTSD). An association has been found between pTSD and substance abuse. pTSD is a severe disorder that should be taken into account when opioids are prescribed. It has been found that the prevalence of opioid use disorder(OUD) in chronic pain patients is higher among those with pTSD than those without this *** To perform a systematic review on the association between pTSD, chronic noncancer pain(CNCp), and opioid intake(i.e., prescription, misuse, and abuse).METHODS We conducted a systematic review following the preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The patient, Intervention,Comparator, and Outcomes(piCOS) criteria were formulated a priori in the protocol of the systematic review. A search was conducted of the pROSpero database. In March 2019, searches were also conducted of 5 other databases:pub Med, MEDLINE, psyc INFO, Web of Science, and piLOTS. The Scottish Intercollegiate Guidelines Network checklist for cohort studies was used to assess the selected studies for their methodological quality and risk of bias. Each study was evaluated according to its internal validity, participant sampling,confounding variables, and the statistical *** A total of 151 potentially eligible studies were identified of which 17 were retained for analysis. Only 10 met the selection criteria. All the studies were published between 2008 and 2018 and were conducted in the United States. The eligible studies included a total of 1622785 unique participants. Of these, 196516 had comorbid CNCp and pTSD and were consuming opiates. The participants had a cross-study mean age of 35.2 years. The majority of participants were men(81.6%). The most common chronic pain condition was musculoskeletal pain:back pain(47.14% across studies;range: 16%-60.6%), arthritis and joint pain(31.1%;range: 18%-67.5%), and

关键词： posttraumatic stress disorder Chronic pain Opioid prescription Opioid misuse Opioid abuse

Metabolic complications in liver transplant recipients

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World Journal of Gastroenterology 2016年第28期22卷 6416-6423页

作者： Miguel Jiménez-pérez roc.. González-Grande Edith Omonte Guzmán Víctor Amo Trillo Juan Miguel Rodrigo López UGC de Aparato Digestivo Unidad de Hepatología-Trasplante Hepático Hospital Universitario Regional de Málaga

The metabolic syndrome(MS), which includes obesity,dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease(CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease(NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS.

关键词： Metabolic syndrome Liver transplantation Immunosuppressions Risk factors Non-alcoholic fatty liver disease