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overcoming mitochondrial dysfunction in neurodegenerative diseases

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Neural Regeneration Research 2023年第7期18卷 1486-1488页

作者： joão Pessoa ana I.Duarte CNC-Center for Neuroscience and Cell Biology CIBB-Center for Innovative Biomedicine and BiotechnologyUniversity of CoimbraCoimbraPortugal

Due to their intense electrical activity,neurons have high energy *** requirement makes them particularly sensitive to mitochondrial *** all eukaryotic cells,neurons have intrinsic mechanisms to mitigate the impact of mitochondrial dysfunction and its consequent production of toxic *** such(neuro)protective mechanisms,mitochondrial autophagy(mitophagy)is responsible for the removal of dysfunctional *** inhibition of mitophagy,together with insufficient mitochondrial activity,results in a shortage of adenosine triphosphate(ATP)and the accumulation of reactive oxygen species(RoS)(Simmons et al.,2020).

关键词： protective dysfunction intense

Impaired T-cell differentiation in diabetic foot ulceration

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Cellular & Molecular Immunology 2017年第9期14卷 758-769页

作者： joão Moura joão rodrigues Marta Gonçalves Cláudia Amaral Margarida Lima Eugénia Carvalho Center for Neuroscience and Cell Biology(CNC) University of Coimbra3004-517 CoimbraPortugal Hospital de Santo Antonio(HSA) Centro Hospitalar do Porto(CHP)4099-001 PortoPortugal Unidade Multidisciplinar de Investigação Biomédica(UMIB/ICBAS/UP) PortoPortugal Department of Geriatrics University of Arkansas for Medical Sciences(UAMS)Little RockAR 72202USA Arkansas Children's Hospital Research Institute(ACHRI) Little RockAR 72202USA

Foot ulceration is one of the most debilitating complications associated with diabetes,but its cause remains poorly *** studies have been undertaken to understand healing kinetics or find possible therapies to enhance ***,few studies have been directed at understanding the immunological alterations that could influence wound healing in *** this study,we analysed the T-cell receptor(TCR)repertoire diversity in TCR-αβ^(+)T *** also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot *** results showed that diabetic individuals,especially those with foot ulcers,have a significantly lower naive T-cell number and a poorer TCR-Vβrepertoire *** also showed that the reduced TCR-Vβrepertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells,the major source of tumour necrosis factor-αproduction,which was even more pronounced in patients with acute foot ***,the expression of several inflammatory chemokine receptors was significantly reduced in diabetic *** conclusion,effector T-cell accumulation and TCR repertoire diversity reduction appear to precede the development of foot *** finding may open new immunological therapeutic possibilities and provide a new prognostic tool in diabetic wound care.

关键词： diabetes T-cells T-cell repertoire diversity wound healing

Genetic variation at the p53 locus of two ecologically divergent Microtus pine voles:identification of molecular markers for species assignment

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Integrative Zoology 2022年第6期17卷 1179-1192页

作者： ana Sofia QUINA joão Paulo TAVANEZ Maria da Luz MATHIAS CESAM-Centro de Estudos do Ambiente e do Mar Departamento de BiologiaUniversidade de AveiroAveiroPortugal CESAM-Centro de Estudos do Ambiente e do Mar Faculdade de CiênciasUniversidade de LisboaLisboaPortugal Departamento de Biologia Animal Faculdade de CiênciasUniversidade de LisboaLisboaPortugal Global Health and Tropical Medicine(GHTM) Instituto de Higiene e Medicina Tropical(IHMT)Universidade NOVA de Lisboa(UNL)Portugal

The Lusitanian(Microtus lusitanicus)and the Mediterranean(Microtus duodecimcostatus)pine voles are recently diverged sister species endemic of the Iberian Peninsula that can be identiﬁed with ecological and morphological characters,but in areas where the 2 species co-occur,species designation may be difﬁ*** discrimination between *** and *** has not been achieved yet possibly because of their estimated re-cent split and an evolutionary history that includes inter-species geneﬂ*** our previous observations on exons 5–7 of the p53 gene,here we analyze the potential use of the p53 genomic region as a discrimination marker of these species by extending our analyses to several kb upstream and downstream of the p53 gene and charac-terizing the degree of genetic differentiation in 7 markers within this ***,we fully sequenced the P53 protein of both *** observed:(i)generally high differentiation in this region;(ii)*** showed in general higher values of nucleotide and haplotype diversities;(iii)the concatenated phylogenetic tree separates the 2 species;(iv)the 2 P53 proteins only differ in 1 amino acid;(v)4 of the markers,2 in p53,one in Atp1b2,and another in Wrap53,contain species-speciﬁc genetic variation thus allowing a reliable discrimination between specimens from both species,irrespective of sampling location or introgression *** provide ad-ditional data on the putative role of p53 in the evolution of these species and present researchers with a fast and cost-effective resource for *** and *** identiﬁcation.

关键词： ecological stress genetic variation Microtus molecular marker p53

A review on the scale-up of high-shear wet granulation processes and the impact of process parameters

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Particuology 2024年第9期92卷 180-195页

作者： ana Rita Alves Marta Filipe Simões Sérgio Simões joão Gomes University of Coimbra CERESDepartment of Chemical EngineeringFaculty of Sciences and TechnologyRua Sílvio Lima3030-790CoimbraPortugal Bluepharma-Indústria Farmacêutica São Martinho do BispoCoimbra3045-016Portugal Faculty of Pharmacy University of CoimbraAzinhaga de Santa Comba3000-548CoimbraPortugal

Wet granulation is one of the most important agglomeration processes,and high-shear granulation(HSG)one of the most employed technologies in the pharmaceutical *** most critical process parameters of HSG are discussed in this *** main concern in scaling up the wet granulation process is the differences between scales,which prevent the particles from having the same experience across all *** scale-up of wet granulation processes is commonly divided into two categories:engineering and attribute-based *** engineering-based scale-up approach is a strategy based on dimensional analysis and an attribute-based supported on the principles of“equifinality”,where process variables are adjusted to obtain equivalent granule *** work presents the effect of different HSG process parameters on the scale-up,as well as the use of process analytical tools(PAT)and modelling *** aim is to review applied scale-up approaches in HSG and discuss benefits and *** is proven why the scale-up for oral solid pharmaceutical products is still considered a hot topic and a very challenging task for development and engineering teams.

关键词： High-shear wetgranulation Parametric-based Attribute-based Physics-based modelling Impeller design Scale-up

The neurosphere assay:an effective in vitro technique to study neural stem cells

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Neural Regeneration Research 2021年第11期16卷 2229-2231页

作者： Rita Soares Filipa F.Ribeiro Diogo M.Lourenço Rui S.rodrigues joão B.Moreira ana M.Sebastião Vanessa A.Morais Sara Xapelli Instituto de Medicina Molecular joão Lobo Antunes Faculdade de MedicinaUniversidade de LisboaLisboaPortugal Instituto de Farmacologia e Neurociências Faculdade de MedicinaUniversidade de LisboaLisboaPortugal Instituto de Biologia Molecular Faculdade de MedicinaUniversidade de LisboaLisboaPortugal

Neural stem cells(NSCs)are known to be present in the adult mammalian brain where they constitutively differentiate into the neuronal,astroglial,and oligodendroglial lineages,in defined processes termed neurogenesis,ast rogl iogenesis and oligodendrogenesis,respectively(reviewed in Braun and Jessberger,2014).During brain development,NSCs are present throughout the brain,becoming progressively restricted to defined brain *** the adult brain,NSCs are mainly present in areas classically known as neurogenic niches,*** subventricular zone(SVZ),along the lateral walls of the lateral ventricles,and the subgranular zone,located in the dentate gyrus(DG)of the hippocampus.

关键词： walls neural becoming

Testicular prostheses-impact on quality of life and sexual function

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Asian journal of Andrology 2024年第2期26卷 160-164页

作者： ana Sofia Araujo Sara anacleto Ricardo rodrigues Catarina Tinoco Andreia Cardoso Carlos oliveira Ricardo Leao Department of Urology Braga's HospitalBraga 4710Portugal Faculty of Medicine Coimbra UniversityCoimbra 3000Portugal

orchiectomy is the recommended treatment for many testicular ***,testicular prosthesis placement is not always performed for different *** this study,we aimed to evaluate patients'opinions and the impact on sexual function and quality of *** retrospective observational single-center study included patients who underwent orchiectomy between January 2014 and December 2020 at the Department of Urology,Braga's Hospital(Braga,Portugal),where testicular implants were always available and the decision to undergo the procedure was made fully independent of *** completed four questionnaires that assessed demographic data,satisfaction,self-esteem,and sexual *** the 96 patients who underwent orchidectomy,59 replied to the questionnaires,and of these patients,86.4%decided to undergo silicone-based testicular prostheses *** remaining 13.6%refused the implant based on concerns about complications(37.5%),because they felt that it was unnecessary(37.5%),or because it was not offered by the doctor(25.0%).overall,96.1%of these patients were satisfied with the implant;however,25.5%classified it as"too firm".No statistically significant differences were found in sexual function(all P>0.05).However,it can be observed that there are more patients with prostheses presenting normal sexual activity compared to patients without prostheses(74.0%vs 50.0%),and none of them reported severe erectile dysfunction(0 vs 16.7%).Regarding self-esteem,both patients with and without prostheses present very similar average scores with no statistically significant *** present study highlights the highest level of satisfaction among patients who received testicular *** prostheses implantation is a safe procedure that does not hamper sexual function after orchiectomy.

关键词： orchiectomy patient satisfaction quality of life sexual dysfunction sexual health testicular prostheses

Hepatic adenomatosis in glycogen storage disease:Radio-pathological correlation

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Hepatobiliary & Pancreatic Diseases International 2021年第6期20卷 579-581页

作者： joão M Louro ana M Alves joséR Brandão Manuela França Department of Radiology Centro Hospitalar Universitário do Porto EPEPorto 4099-001Portugal Department of anatomical Pathology Centro Hospitalar Universitário do Porto EPEPorto 4099-001Portugal

Glycogen storage disease type I(GSD type I),also known as von Gierke disease,is an autosomal recessive disorder of the glycogen metabolism pathway,caused by a deficiency of glucose-6-phosphatase(GSD type Ia)or glucose... 详细信息

关键词： 1] metabolism trans

Liquid chromatographic methods for determination of the new antiepileptic drugs stiripentol, retigabine, rufinamide and perampanel: A comprehensive and critical review

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journal of Pharmaceutical analysis 2021年第4期11卷 405-421页

作者： Sara Meirinho Marcio rodrigues ana Fortuna Amílcar Falcao Gilberto Alves Faculty of Health Sciences Health Sciences Research CenterUniversity of Beira Interior(CICS UBI)6200-506CovilhaPortugal Research Unit for Inland Development Polytechnic Institute of Guarda(UDI-IPG)6300-654GuardaPortugal Coimbra Institute for Biomedical Imaging and Translational Research(CIBIT) University of Coimbra3000-548CoimbraPortugal Laboratory of Pharmacology Faculty of PharmacyUniversity of Coimbra3000-548CoimbraPortugal

The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy *** them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be ***,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system *** different liquid chromatographic(LC)methods coupled with ultraviolet,fluorescence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet ***,this review summarizes the main analytical aspects regarding the liquid chromatographic methods developed for the analysis of perampanel,retigabine(and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage ***,the physicochemical and stability properties of the target compounds will also be ***,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new(bio)analytical techniques are aimed to be implemented for these drugs.

关键词： Bioanalysis Liquid chromatography Perampanel Retigabine Rufinamide Stiripentol

Genoprotection and metabolic benefits of marine macroalgae-Insights into the concept of functional foods through direct and indirect consumption

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Food Bioscience 2022年第3期47卷 524-533页

作者： ana Marques joão Ferreira ana Cerqueda-Pacheco Vitória Pereira Helena Abreu Rui Pereira Maria joão Pires Fernanda Seixas Paula oliveira Isabel Gaivão Mário Pacheco Laboratory of Physiotoxicology CESAM-Centre for Environmental and Marine StudiesDepartment of BiologyUniversity of AveiroCampus Universitário de Santiago3810-193AveiroPortugal CECAV-Animal and Veterinary Research Center AL4AnimalsUniversity of Trás-os-Montes and Alto DouroQuinta de Prados5000-801Vila RealPortugal Department of Genetics and Biotechnology University of Trás-os-Montes and Alto DouroQuinta de Prados5000-801Vila RealPortugal Department of Biology and Environment University of Trás-os-Montes and Alto DouroQuinta de Prados5000-801Vila RealPortugal CITAB-Centre for the Research and Technology of Agro-Environmental and Biological Sciences Inov4AgroUniversity of Trás-os-Montes and Alto DouroQuinta de Prados5000-801Vila RealPortugal Department of Veterinary Sciences University of Trás-os-Montes and Alto DouroQuinta de Prados5000-801Vila RealPortugal ALGAplus Lda.Travessa Alexandre da Conceição s/n3830-196ÍlhavoPortugal

The consumption of marine macroalgae has been linked with health benefits,albeit some actions,including genoprotection,remain ***,we evaluated the genoprotective potential of a mixture of Ulva rigida,Fucus vesiculosus and Gracilaria gracilis,through direct consumption or via indirect intake using fish(Sparus aurata)as a vector of algal ***(Mus musculus)were subjected to a 1-month dietary supplementation with 5%of macroalgae mix or 10%of fillet of fish previously fed with an algae-supplemented aquafeed(for comparison purposes,10%supplementation with fillet of fish standardly fed was also considered).Thereafter,mice were challenged by the genotoxicant methyl methanesulfonate(MMS),and the genetic damage was evaluated through the micronuclei ***,a wider evaluation was carried out encompassing the assessment of energy metabolism,haematological and histological parameters,as well as growth *** unequivocally protected against MMS-induced *** activity profile of hepatic lactate and isocitrate dehydrogenases promoted by the supplemented diets reflected an improved energy *** properties were not transferred via fish fed with the algae-supplemented aquafeed,though the transference of phytocomponents with beneficial properties(*** balance improvement)should not be ***,these findings highlighted the genoprotection afforded by marine macroalgae,likely promoted by desmutagenic factors,reinforcing their definition as functional *** possibility of using fish as an indirect source of algae-borne phytocomponents proved to be plausible and worthy of further investigations.

关键词： Antigenotoxicity Desmutagens Fish consumption Functional food Marine macroalgae consumption Metabolic benefits