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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 rocío 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 rocío 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 process 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

Presynaptic endoplasmic reticulum architecture and hereditary spastic paraplegia

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Neural Regeneration Research 2024年第3期19卷 485-486页

作者： Juan JoséPérez-Moreno Instituto de Biomedicina de sevilla(IBis) Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevillaand Departamento de Biología CelularFacultad de BiologíaUniversidad de SevillaSevilleSpain

Hereditary spastic paraplegia(HsP)is a clinically and genetically heterogeneous neurodegenerative disorder,characterized primarily by progressive spasticity and weakness in the lower *** ients can also experience peripheral neuropathy,cognitive impairment,and other neurological *** date,more than 80 genes have been implicated in HsP,encompassing various cellular components,although mutations in genes encoding endoplasmic reticulum(ER)-shaping proteins are the most prevalent(Parodi et al.,2017).ER-shaping proteins are generally known for regulating the tubulation and curvation of the ER,but most of them show additional functions,including fusion of ER tubules,microtubule-severing,ER autophagy,lipid droplet synthesis,contact sites with other organelles(Öztürk et al.,2020).This highlights the complexity of studying the role of these proteins and the link between ER function and HsP.

关键词： reticulum endoplasmic

Hydroxytyrosol and Parkinson's disease:protective actions against alpha-synuclein toxicity

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Neural Regeneration Research 2024年第7期19卷 1427-1428页

作者： Ruth Hornedo-ortega ana M.Espinosa-oliva Departamento de Nutrición y Bromatología Toxicología y Medicina LegalFacultad de FarmaciaUniversidad de SevillaSevilleSpain Instituto de Biomedicina de sevilla IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Departamento de Bioquímica y Biología Molecular Facultad de FarmaciaUniversidad de SevillaSevillaSpain

Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of *** to data from the World Health organization(WHo),its prevalence has doubled in the past 25 *** 2019,global estimates indicated over 8.5 million individuals with PD and it is suggested that PD caused 329000 deaths,an increase of over 100% since 2000(WHo,2022).

关键词： protective Alzheimer prevalence

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 rocío 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

Is the near coming xenotransplantation era relieving us from needing to look for more non-living organ donors?

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World Journal of Transplantation 2022年第12期12卷 388-393页

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

Despite organ transplantation being the most successful treatment for end-stage organ dysfunction,the number of annual solid organ transplantations is much lower than that required to satisfy the demand of patients on waiting *** explanation for this phenomenon is the relative scarcity of non-living organ donors due to several factors,such as:(1)Late arrival of patients with a neurocritical condition to an emergency service;(2)lack of detection of those patients as possible organ donors by health professionals dedicated to procurement or by clinicians at emergency and intensive care units,for instance;(3)late transfer of the patient to an intensive care unit to try to recover their health and to provide hemodynamic,ventilatory,and metabolic support;(4)lack of confirmation of the physiological status of the possible donor;(5)late or incorrect positive diagnosis of the subject’s death,either due to brain or cardiac death;(6)difficulty in obtaining legal authorization,either by direct relatives or by the authority,for the extraction of organs;and(7)deficient retrieval surgery of the organs actually *** recent reports of relatively successful xenotransplants from genetically modified pigs open the possibility to fix this mismatch between supply and demand,but some technical(organ rejection and opportunistic infections),and economic issues,still remain before accepting a progressive replacement of the organ sources for *** approximate economic cost analysis suggests that the hypothetical acquisition cost of any genetically modified pig derived organ is high and would not even satisfy the solid organ demand of the wealthiest countries.

关键词： organ donation Xenotransplantation Procurement Kidney transplantation Costs

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 rocío 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 (osing cholestatic hepatitis, 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

Toll-like receptor 4 and protease-activated receptor 2 in physiology and pathophysiology of the nervous system:more than just receptor cooperation?

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Neural Regeneration Research 2019年第7期14卷 1196-1201页

作者： Darius Widera rocío Martínez Aguilar Graeme s.Cottrell stem Cell Biology and Regenerative Medicine Group School of PharmacyUniversity of ReadingWhiteknights campus Unidad de Inmunología IBIMERUniversidad de Granada Cellular and Molecular Neuroscience School of PharmacyUniversity of Reading

Toll-like receptor 4(TLR4) and protease-activated receptor 2(PAR2) play pivotal roles in the mammalian innate immune ***,in addition to their involvement in detection of invading pathogens,PAR2 and TLR4 modulate the levels of cell death-induced sterile inflammation by activating pro-or anti-inflammatory downstream signaling *** the central nervous system,there is emerging evidence that both receptors are involved in synaptic transmission and brain ***,due to their prominent role in mediating neuroinflammation,PAR2 and TLR4 are associated with development and progression of neurodegenerative disorders including but not limited to Alzheimer's disease,Parkinson's disease and multiple *** this article,we summarise the current knowledge on the cooperation between PAR2 and TLR4,discuss the potential cross-talk levels and highlight the impact of the cross-coupling on neuroinflammation.

关键词： signaling inflammation proteases myeloid of differentiation primary response gene 88 TIR-domain containing adaptor inducing interferon lipopolysaccharide TLR4 PAR2

Prevalence of hepatocarcinoma-related hepatitis B virus mutants in patients in grey zone of treatment

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World Journal of Gastroenterology 2019年第38期25卷 5883-5896页

作者： ana Isabel Gil-García Antonio Madejón Irene Francisco-Recuero ana López-López Emiliana Villafranca Miriam Romero Araceli García Antonio olveira rocío Mena Juan ramón Larrubia Javier García-samaniego Hepatology Unit Hospital Universitario La PazMadrid 28046Spain Centro de Investigación Biomédica en Red Instituto de Salud Carlos IIIMadrid 28029Spain Instituto de Investigación del Hospital Universitario la Paz Madrid 28046Spain Biochemistry Department Faculty of MedicineUniversidad Autónoma de MadridMadrid 28029Spain Instituto de Genética Médica y Molecular Hospital Universitario La PazMadrid 28046Spain Translational Hepatology Unit Hospital General Universitario de GuadalajaraGuadalajara 19002Castilla-La ManchaSpain

BACKGRoUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health *** this sense,the identification of HBV mutants related with an increased risk of hepatocellular carcinoma(HCC)could be useful to identify subpopulations with potential indication of antiviral *** To analyze the prevalence/persistence of hepatitis B virus(HBV)pres and basal core promoter(BCP)/precore/core variants associated to HCC development in CHB patients in the grey *** Work was designed as a longitudinal retrospective study,including 106 plasma samples from 31 patients with CHB in the grey zone of treatment:Hepatitis B e antigen negative,HBV-DNA levels between 12-20000 IU/mL,normal or discordant transaminase levels during follow up and mild/moderate necroinflammatory activity in liver biopsy or Fibroscan(up to 9.5 kPa).serum HBVDNA was tested using the Abbott Real Time HBV Assay and the BCP/precore/core and the hepatitis B surface antigen(HBsAg)coding regions were analyzed in positive samples by PCR/bulk-sequencing to identify the HCCrelated HBV *** High-risk HCC related mutants were detected in 24(77%)patients:19(61%)in the BCP/precore/core,and 7(23%)in the HBsAg coding region(2 pres1 and 5 pres2 deletions).The prevalence of pres deletions was genotype-dependent:3/5(60%)patients with pres2 deletions and 1/2 with pres1 deletions were infected with the HBV-E *** HBV-E was the most prevalent in sub-saharan patients,a correlation between pres deletions and ethnicity was also found:6/8(75%)sub-saharan vs 1/19(5%)Caucasian patients had pres deletions(P=0.00016).Remarkably,this correlation was maintained in those patients infected with HBV-A,a minor genotype in sub-saharan patients:2/2 patients infected with HBV-A from West Africa vs 0/6 of Caucasian origin had pres *** HCC related variants were the major strains and persisted over time(up to 48 mo).Pa

关键词： Hepatitis B virus Hepatocellular carcinoma Pres deletions Hepatitis B virus treatment Grey zone