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Cell-based therapeutic strategies for treatment of spinocerebellar ataxias:an update

Neural Regeneration Research 2023年第6期18卷 1203-1212页

作者： joana sofia correia Sara Duarte-Silva António JoséSalgado Patrícia Maciel Life and Health Sciences Research Institute(ICVS) School of MedicineUniversity of MinhoBragaPortugal ICVS/3B’s–PT Government Associate Laboratory BragaGuimarãesPortugal

Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion,which encodes a long glutamine tract(polyglutamine)in the respective wild-type protein causing misfolding and protein *** features of polyglutamine spinocerebellar ataxias include neuronal aggregation,mitochondrial dysfunction,decreased proteasomal activity,and autophagy *** polyglutamine protein aggregates accumulate within neurons and cause neural dysfunction and death in specific regions of the central nervous *** ataxias are mostly characterized by progressive ataxia,speech and swallowing problems,loss of coordination and gait *** the past decade,efforts have been made to ameliorate disease symptoms in patients,yet no cure is *** studies have been proposing the use of stem cells as promising tools for central nervous system tissue *** far,pre-clinical trials have shown improvement in various models of neurodegenerative diseases following stem cell transplantation,including animal models of spinocerebellar ataxia types 1,2,and ***,contrasting results can be found in the literature,depending on the animal model,cell type,and route of administration ***,clinical trials using cellular implants into degenerated brain regions have already been applied,with the expectation that these cells would be able to differentiate into the specific neuronal subtypes and re-populate these regions,reconstructing the affected neural ***,the question of how feasible it is to continue such treatments remains unanswered,with long-lasting effects being still *** establish the value of these advanced therapeutic tools,it is important to predict the actions of the transplanted cells as well as to understand which cell type can induce the best outcomes for each *** studies are needed to determine the best route of administration,without neglec

关键词： cell transplantation engraftment induced pluripotent stem cells mesenchymal stem cells neural progenitor cells neuroprotection polyglutamine spinocerebellar ataxias secretome spinocerebellar ataxia stem cell therapy

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Alpha-1 antitrypsin deficiency and Pi*Z allele as important co-factors in the development of liver fibrosis

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World Journal of Hepatology 2024年第8期16卷 1099-1110页

作者： Ana Isabel Ferreira Catarina Guimarães Vitor Macedo Silva sofia Xavier joana Magalhães JoséCotter Department of Gastroenterology Hospital da Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal Life and Health Sciences Research Institute School of MedicineUniversity of MinhoBraga 4710-057Portugal Life and Health Sciences Research Institute/3B’s PT Government Associate LaboratoryBraga 4710-057Portugal Department of Pulmonology Hospital Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant *** To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver *** Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology *** Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi**** age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/*** created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

关键词： Alpha-1 antitrypsin deficiency Liver fibrosis Nonalcoholic fatty liver disease fibrosis score Fibrosis-4 index Liver stiffness measurement

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Dynamics of Droplets of Biological Fluids on Smooth Superhydrophobic Surfaces under Electrostatic Actuation

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Journal of Bionic Engineering 2016年第2期13卷 220-234页

作者： Ana sofia Moita Catarina Laurencia joana Anastacio Ramos Duarte Miguel Franca Prazeres Antonio Luis Nobre Moreira IN+ - Center for Innovation Technology and Policy Research Instituto Superior Tecnico Universidade de Lisboa Av. Rovisco Pais 1049-001 Lisboa Portugal iBB - Institute for Bioengineering and Biosciences Department of Bioengineering Instituto Superior Tecnico Universidade de Lisboa Av. Rovisco Pais 1049-001 Lisboa Portugal

This study describes the dynamic behaviour of droplets of biological liquids on hydrophobic surfaces under electrostatic actuation, to devise sample handling in lab-on-chip diagnostic tools. Bovine Serum Albumin （BSA） is taken as a representative biomolecule, since it is often used in adsorption studies. Green Fluorescence Protein （GFP） is also considered, given its natural fluorescence. Several effects such as sample concentration and pH are discussed. The results show negligible effects of proteins concentration in electrowetting, although increased concentrations endorse passive adsorption mechanisms, which alter the local wettability of the substrates precluding droplet motion. Bioinspired surfaces promote the largest spreading diameter, which is beneficial for droplet motion. However, surface roughness promotes energy dissipation limiting the receding droplet motion. Hence, the most effective approach is altering the surface chemistry. The coating is applied to a surface with a mean roughness smaller than 20 nm and does not alter significantly the topography, thus leading to the so-called smooth superhydrophobic surface. This coating also reduces passive proteins adsorption, as confirmed by Confocal Microscopy （CM）, which is beneficial for droplet motion. Evaluating absorption spectra of protein solutions evidences an increase in protein concentration ascribed to droplet evaporation as confirmed by theoretical analysis and time resolved infrared visualization.

关键词： bioinspired surfaces biofluids electrostatic actuation hydrophobicity adsorption evaporation

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Neutrophile-to-lymphocyte,lymphocyte-to-monocyte,and platelet-tolymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2022年第7期14卷 1307-1323页

作者： Tiago Cruz Tomás Ines Eiriz Marina Vitorino Rodrigo Vicente Joao Gramaca Alicia Guadalupe Oliveira Paulo Luz Mafalda Baleiras Ana sofia Spencer Luísa Leal Costa Patrícia Liu joana Mendonca Magno Dinis Teresa Padrao Marisol correia Goncalo Atalaia Michelle Silva Teresa Fiúza Department of Medical Oncology Hospital Professor Doutor Fernando Fonseca EPEAmadora 2720-276Portugal Department of Medical Oncology Centro Hospitalar Barreiro-Montijo EPEBarreiro 2830-003Portugal Department of Medical Oncology Hospital do Espírito Santo deÉvora EPEÉvora 7000-811Portugal Department of Medical Oncology Centro Hospitalar Universitário do Algarve EPEAlgarve 8000-386Portugal Department of Medical Oncology Hospital São Francisco XavierCentro Hospitalar Lisboa Ocidental EPELisboa 1449-005Portugal Department of Medical Oncology Hospital Santo António dos CapuchosCentro Hospital Lisboa Central EPELisboa 1169-050Portugal Department of Medical Oncology Hospital BeatrizÂngeloLoures 2674-514Portugal Department of Medical Oncology Centro Hospitalar de Trás-os-Montes e Alto Douro EPEVila Real 5000-508Portugal Department of Medical Oncology Hospital da Senhora da Oliveira EPEGuimarães 4835-044Portugal Department of Medical Oncology Hospital Garcia de Orta EPEAlmada 2805-267Portugal Department of Medical Oncology Hospital da LuzLisboa 1500-650Portugal Department of Medical Oncology Hospital Distrital de Santarém EPESantarém 2005-177Portugal

BACKGROUND Perioperative fluorouracil plus leucovorin,oxaliplatin,and docetaxel(FLOT)improves prognosis in locally advanced gastric cancer(LAGC).Neutrophil-to-lymphocyte(NLR),lymphocyte-tomonocyte(LMR),and platelet-to-lymphocyte(PLR)ratios are prognostic biomarkers but not predictive *** To assess blood ratios’(NLR,LMR and PLR)potential predictive response to FLOT and survival outcomes in resectable LAGC *** This was a multicentric retrospective study investigating the clinical potential of NLR,LMR,and PLR in resectable LAGC patients,treated with at least one preoperative FLOT cycle,from 12 Portuguese *** were compared through non-parametric Mann-Whitney *** operating characteristic curve analysis defined the cut-off values as:High PLR>141 for progression and>144 for mortality;high LMR>3.56 for T stage regression(TSR).Poisson and Cox regression models the calculated relative risks/hazard ratios,using NLR,pathologic complete response,TSR,and tumor regression grade(TRG)as independent variables,and overall survival(OS)as the dependent *** This study included 295 patients(mean age,63.7 years;59.7% males).NLR was correlated with survival time(r=0.143,P=0.014).PLR was associated with systemic progression during FLOT(P=0.022)and mortality(P=0.013),with high PLR patients having a 2.2-times higher risk of progression[95% confidence interval(CI):0.89-5.26]and 1.5-times higher risk of mortality(95%CI:0.92-2.55).LMR was associated with TSR,and high LMR patients had a 1.4-times higher risk of achieving TSR(95%CI:1.01-1.99).OS benefit was found with TSR(P=0.015)and partial/complete TRG(P<0.001).Patients without TSR and with no evidence of pathological response had 2.1-times(95%CI:1.14-3.96)and 2.8-times(95%CI:1.6-5)higher risk of *** Higher NLR is correlated with longer survival *** LMR patients have a higher risk of decreasing T stage,whereas high PLR patients have higher odds of progressing under FLOT a

关键词： Gastric cancer Perioperative fluorouracil plus leucovorin,oxaliplatin,and docetaxel Neutrophil-to-lymphocyte Lymphocyte-to-monocyte Platelet-to-lymphocyte Tumor regression grade

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Novel synthetic opioids-toxicological aspects and analysis

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Forensic Sciences Research 2019年第2期4卷 111-140页

作者： Inês Tabarra sofia Soares Tiago Rosado joana Gonçalves Àngelo Luís Sara Malaca Mário Barroso Thomas Keller José Restolho Eugenia Gallardo Centro de Investigação em Ciências da Saude(CICS-UBI) Universidade da Beira InteriorCovilhãPortugal Laboratorio de Fármaco-Toxicologia-UBIMedical Universidade da Beira InteriorCovilhãPortugal Serviço de Química e Toxicologia Forenses Instituto Nacional de Medicina Legal e Ciências ForensesDelegac¸ão do SulLisboaPortugal Departament of Toxicology Institute of Forensic MedicineSalzburgAustria nal von minden GmbH RegensburgGermany

Over the past few years,there has been an emerging number of new psychoactive *** drugs are frequently mentioned as“legal highs”,“herbal highs”,“bath salts”and“research chemicals”.They are mostly sold and advertised on online forums and on the dark *** emerging new psychoactive substances are designed to mimic the effects of psychoactive groups,which are often abused *** synthetic opioids are a new trend in this context and represent an alarming threat to public *** the wide number of fatalities related to these compounds reported within the last few years,it is an important task to accurately identify these compounds in biologic matrices in order to administer an effective treatment and reverse the respiratory depression caused by opioid related *** dealing with fentanyl intoxication cases should consider that it could,in fact,be a fentanyl *** this reason,it is a helpful recommendation to include synthetic opioids in the routine toxicological screening procedures,including analysis in alternative matrices,if available,to investigate poly-drug use and possible tolerance to *** address this public health problem,better international collaboration,effective legislation,effective investigation,control of suspicious“research chemicals”online forums and continuous community alertness are *** article aims to review diverse reported fatalities associated with new synthetic opioids describing them in terms of pharmacology,metabolism,posology,available forms,as well as their toxic effects,highlighting the sample procedures and analytical techniques available for their detection and quantification in biological matrices.

关键词： Forensic sciences forensic toxicology new synthetic opioids biological specimens toxicity analysis

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Lanthanide complexes with β-diketones and coumarin derivates:synthesis,thermal behaviour,optical and pharmacological properties and immobilisation

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Journal of Rare Earths 2010年第S1期28卷 66-74页

作者： Maria Milanova joana Zaharieva Iliya Manolov Miroslava Getzova Dimitr To dorovsky Department of Inorganic Chemistry University of SofiaBulgaria 1J. Bourc hier Blvd.1164 SofiaBulgaria Department of Organic Chemistry Medical Un iversity2Dunav Str.1000 SofiaBulgaria

The paper presents the results of the synthesis of complexes of the ty pe Eu(DBM) 3 and Eu(DBM) 3·Q(DBM-dibenzoylmethane,Q-1,10-phenantroline or 4,7-d iphenyl-1,10-phenantroline) and of Tb-and Nd-complexes with the newly-synthesis ed coumarin derivates 3,3’-[(4-chlorphenyl) methylene) bis(4-hydroxy-2H-chromen-2-one) ,3,3’-[(3,5-dimethoxy-4-hydroxy) methylene) bis(4-hydroxy-2H-chromen-2-one) ,etc. Elemental and thermogravimetric analysis,IR,UV,NMR and fluorescence spe ctroscopy and X-ray analysis were applied for characterisation of the complexes. Some peculiarities of the synthetic procedures for both types of complexes were discussed and the influence of the synthetic approach,pH of the reaction mediu m,temperature of synthesis and drying of the complexes on the composition,stab ility and optical properties was reported. The immobilisation of the complexes i n thin films based on sol-gel produced SiO2 and on polymethylmethacrylate was st udied. The optimal conditions for preparation of the matrices(composition of th e starting system,temperature and time of sol aging,etc.) were recommended. Th e film morphology was evaluated by fluorescence,scanning electron and atomic fo rce microscopy. The interaction of the lanthanide ions with the matrices and the influence of their nature,the effect of the in-situ polymerisation and other f actors on photoluminescent excitation and emission spectra and excited state lif e-times of the complexes were followed. The effect of the second ligand on the p hotoluminescence properties of the immobilised diketonates was further elucidate d. Processes involved in the thermal decomposition of the complexes and microcom posites produced on their base were proposed. Preliminary results on the pharmac ological properties of the coumarin complexes reported showed unambiguously high er cytotoxicity of the Nd complex in comparison with that of the respective ligand.

关键词： rare earths complexes thin films β-diketones coumarin derivates optical properties pharmacological properties morphology

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Current role and future perspectives of cardiac rehabilitation in coronary heart disease

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World Journal of Cardiology 2021年第12期13卷 695-709页

作者： Eduardo M Vilela Ricardo Ladeiras-Lopes Ana Joao joana Braga Susana Torres sofia Viamonte José Ribeiro Madalena Teixeira José P Nunes Ricardo Fontes-Carvalho Department of Cardiology Centro Hospitalar de Vila Nova de Gaia/EspinhoVila Nova de Gaia 4434-502Portugal Department of Surgery and Physiology Cardiovascular Research Unit(UnIC)Faculty of MedicineUniversity of PortoPorto 4200-319Portugal Centro de Reabilitação do Norte Centro Hospitalar de Vila Nova de Gaia/EspinhoVila Nova de Gaia 4405-565Portugal Faculty of Medicine University of PortoPorto 4200-319Portugal

Ischaemic heart disease(IHD)is a major cause of morbidity and mortality *** there have been major advances in this field,these patients are still a higher risk *** such,strategies to mitigate risk and tailor secondary prevention measures are of the utmost *** rehabilitation(CR),encompassing several domains including exercise training,cardiovascular risk factor optimization,nutritional and psychological assessments,as well as other ancillary interventions has shown to be one of the pillars in the contemporary management of patients with ***,CR is associated with several benefits in this population,ranging from functional capacity to improvements in *** this,there are still several issues concerning the optimal application of CR which are still not fully ascertained,such as lack of referral and completion,as well as questions related to programme design(particularly among patients with multiple comorbidities).In this review,we aim at presenting a pragmatic overview on the current role of CR in the management of individuals with IHD,while also discussing some of the caveats in the current data,as well as future concepts which could help improve the uptake and personalization of this pivotal time-tested intervention.

关键词： Cardiac rehabilitation Secondary prevention Myocardial infarction Ischaemic heart disease Cardiovascular diseases

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Endoscopic ultrasonography-emerging applications in hepatology

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World Journal of Gastrointestinal Endoscopy 2017年第8期9卷 378-388页

作者： joana Magalhaes Sara Monteiro sofia Xavier Sílvia Leite Francisca Dias de Castro JoséCotter Gastroenterology Department Hospital Senhora da Oliveira School of Medicine University of Minho Life and Health Sciences Research Institute/3B’s PT Government Associate Laboratory

The inspection of the liver is a valuable part of the upper endoscopic ultrasonography(EUS) studies,regardless of the primary indication for the *** detailed images of the liver segments provided by EUS allows the use of this technique in the study of parenchymal liver disease and even in the diagnosis and classification of focal liver *** has also emerged as an important tool in understanding the complex collateral circulation in patients with portal hypertension and their clinical and prognostic ***,EUS-guided portal vein catheterization has been performed for direct portal pressure measurement as an alternative method to evaluate portal *** this review,the authors summarize the available evidence regarding the application of EUS to patients with liver diseases and how we can apply it in our current clinical practice.

关键词： Endoscopic ultrasonography Portal hypertension Gastroesophageal varices Focal liver lesions Liver biopsy

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Adenosine A2A receptors induce the formation of abnormal secondary axons in rat hippocampal neurons: a new target to arrest epileptogenesis

Adenosine A2A receptors induce the formation of abnormal sec...

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中国神经科学学会第十二届全国学术会议

作者： Xinli Xu sofia Al?ada-Morais Nélio M.Gon?alves joana M.Marques Sergio Valbuena Rui O.Beleza Francisco Q.Gon?alves sofia Ferreira Juan Lerma Rodrigo A.Cunha Ricardo J.Rodrigues CNC-Center for Neuroscience and Cell Biology University of Coimbra

Current anti-epileptic drugs mostly control convulsions with a limited efficacy, and do not seize epileptogenesis. One of the structural-functional modifications occurring during epileptogenesis is an abnormal axonal sprouting. The hippocampal mossy fiber(MF) sprouting found in patients and in animal models of temporal lobe epilepsy(TLE)(Neuroscience14, 375-403) generates an aberrant excitatory feedback circuit in granule cells that is thought to contribute to the hyperexcitability underlying the seizure-prone state(Neurochem. Res.28, 1649-58). However, the mechanism underlying this aberrant re-wiring is still poorly understood. There is now a growing evidence for a sustained increase in extracellular ATP levels in different pathological conditions, prompting ATP as a danger signal in the brain(Front. Neurosci.9:148). Accordingly, we now measured a sustained increase of the evoked release of ATP from hippocampal nerve terminals of Sprague-Dawley rats subjected to Status Epilepticus(SE) induced by pilocarpineinjection. Concomitantly, we found in developing rat hippocampal neurons that the pharmacological activation of adenosine A receptors(ARs) with the selective agonist CGS21680(30 n M) induces the formation of abnormal secondary axons. This prompted us to propose that this abnormal sprouting is due to an abnormal reactivation of the developmental-related AR-driven axon formation and outgrowth. We have now found in hippocampal organotypic slices that the spontaneous MF sprouting was attenuated by the pharmacological blockade of ARs, since the current densities(p A/p F) recorded were significantly lower in the slices cultured in the presence of the selective AR antagonist SCH58261(100 n M). More importantly, we found that the animals subjected to a long-term systemic treatment with SCH58261(0.1 mg/kg, i.p.), beginning 10 hours after pilocarpine-induced SE in rats, displayed significantly less hippocampal MF sprouting. Interestingly, CD73 knockout(CD73 KO) mice(lackin

关键词： A2A receptors Mossy fiber sprouting Status epilepticus CD73

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嘉卿会所-台丰高尔夫俱乐部

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现代装饰 2022年第4期 14-21页

作者： álvaro Siza Carlos Castanheira Elisabete Queirós Catarina Araújo Erika Musci Filipe Mota joana Soeiro Jo?o Alves Jorge Pinheiro Mariana Mendes Nuno Campos Nuno Rodrigues Pedro Afonso Rita Saturnino Sara Pinto sofia Concei??o Carlos Castanheira 范嘉苑

在高尔夫球运动中,力量与优雅的完美平衡是衡量其水平的一个基本准则。同样的,在建筑设计与建造的表达过程中,除了回应技术问题与基本需求以外,还需要考虑其他或简单或复杂的因素。衡量一个项目不仅只是看基本要素,即使它仅需要回应基...

在高尔夫球运动中,力量与优雅的完美平衡是衡量其水平的一个基本准则。同样的,在建筑设计与建造的表达过程中,除了回应技术问题与基本需求以外,还需要考虑其他或简单或复杂的因素。衡量一个项目不仅只是看基本要素,即使它仅需要回应基础功能。好的设计应该经过谨慎的思考,由此承载巨大能量,传达优雅气息。“经验分析”能够帮助我们辨别设计的第一步,它可能源自于一种态度、概念,或者一些难以解释的想法。

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