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Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro joana Figueiro-silva Neurodegenerative Diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

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Evaluation of Novel 3D Architectures Based on Knitting Technologies for Engineering Biological Tissues

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Journal of Donghua University(English Edition) 2013年第5期30卷 421-426页

作者： RIBEIRO Viviana Pinto RIBEIRO Ana Soares silva carla joana DURES Nelson Feio BONIFCIO Graa CORRELO Vitor Manuel MARQUES Alexandra Pinto SOUSA Rui Amandi OLIVEIRA Ana Leite REIS Rui Luís 3B's Research G roup-Biomaterials Biodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine ICVS /3B's-PT G overnment Associated Laboratory University of Minho CeNTI Centre for Nanotechnology and Smart MaterialsV. N. CITEVE Technological Centre for Textile and Clothing IndustryV. N. CBQF-School of Biotechnology Portuguese Catholic University

Textile-based technologies are considered as potential routes for the production of 3D porous architectures for tissue engineering( TE) applications. We describe the use of two polymers,namely polybutylene succinate( PBS) and silk fibroin(SF) to produce fiber-based finely tuned porous architectures by weft and warp knittings. The obtained knitted constructs are described in terms of their morphology, mechanical properties,swelling ability,degradation behaviour,and cytotoxicity. Each type of polymer fibers allows for the processing of a very reproducible intra-architectural scaffold geometry,with distinct characteristics in terms of the surface physicochemistry,mechanical performance,and degradation capability,which has an impact on the resulting cell behaviour at the surface of the respective biotextiles. Preliminary cytotoxicity screening shows that both materials can support cell adhesion and proliferation. Furthermore, different surface modifications were performed( acid /alkaline treatment, UV radiation,and plasma) for modulating cell behavior. An increase of cell-material interactions were observed,indicating the important role of materials surface in the first hours of culturing. Human adipose-derived stem cells( hASCs) became an emerging possibility for regenerative medicine and tissue replacement therapies. The potential of the recently developed silk-based biotextile structures to promote hASCs adhesion,proliferation,and differentiation is also evaluated. The obtained results validate the developed constructs as viable matrices for TE applications. Given the processing efficacy and versatility of the knitting technology, and the interesting structural and surface properties of the proposed polymer fibers,it is foreseen that our developed systems can be attractive for the functional engineering of tissues such as bone,skin,ligaments or cartilage and also for develop more complex systems for further industrialization of TE products.

关键词： textile-based technologies silk polybutylene succinate(PBS) surface modifications human adipose-derived stem cells(hASCs) tissue engineering(TE)

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Combinatorial therapies for spinal cord injury repair

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Neural Regeneration Research 2025年第5期20卷 1293-1308页

作者： carla S.Sousa Andreia Monteiro António J.Salgado Nuno A.silva Life and Health Sciences Research Institute(ICVS) School of MedicineUniversity of MinhoCampus de Gualtar-gualtarBragaPortugal ICVS/3B’s Associate Lab PT Government Associated LabCampus de Gualtar-gualtarBragaPortugal

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

关键词： electric stimulation neural tissue regeneration neuroprotection polytherapy spinal cord injury

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History Teacher Training from Decolonial Curriculum Practices to Combat Racism at UniProjeção in the Federal District-A Secondary Publication

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Journal of Contemporary Educational Research 2024年第2期8卷 187-202页

作者： Karoline da silva Ramos Cláudia Pinheiro Nascimento Francisca carla Santos Ferrer Faculty of Philosophy Languages and Human SciencesUniversity of São PauloSão PauloBrazil

This article aims to understand the training process of history undergraduates,to see if there are decolonial curricular practices to combat racism at the Centro Universitário e Faculdade Projeção(UniProjeção)in the Federal District,to understand how coloniality has corroborated the exclusion of different epistemologies and the erasure of different cultures,and how this exclusionary process of coloniality interferes in the training of history *** order to combat this practice,we are looking for alternatives that can break these suppressions carried out by *** this way,we turn to decolonial ideas that aim to break with the logic of *** can conclude that these practices are poorly developed in the institution,so we proposed active problem-based methodology and music as a didactic *** playful educational tools that strengthen the teaching-learning process,they are active agents in the decolonial work of combating racism,and it is essential to train responsible and ethical teachers in the fight against racism and any form of oppression.

关键词： Coloniality Decoloniality Education Curriculum practices Racism

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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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Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy

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World Journal of Gastroenterology 2024年第6期30卷 579-598页

作者： Fabian Fellipe Bueno Lemos Caroline Tianeze de Castro Marcel silva Luz Gabriel Reis Rocha Gabriel Lima Correa Santos Luís Guilherme de Oliveira silva Mariana Santos Calmon Cláudio Lima Souza Ana carla Zarpelon-Schutz Kádima Nayara Teixeira Dulciene Maria de Magalhães Queiroz Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Instituto de Saúde Coletiva Universidade Federal da BahiaSalvador 40110040BahiaBrazil Campus Toledo Universidade Federal do ParanáToledo 85919-899ParanáBrazil Laboratory of Research in Bacteriology UFMGBelo Horizonte 30130-100Minas GeraisBrazil

BACKGROUND Helicobacter pylori(***)infection has been well-established as a significant risk factor for several gastrointestinal *** urea breath test(UBT)has emerged as a leading non-invasive method for detecting *** numerous studies confirming its substantial accuracy,the reliability of UBT results is often compromised by inherent *** findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of *** *** To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for *** infection in adult patients with *** We conducted an independent search of the PubMed/MEDLINE,EMBASE,and Cochrane Central databases until April *** search included diagnostic accuracy studies that evaluated at least one of the index tests(^(13)C-UBT or ^(14)C-UBT)against a reference *** used the QUADAS-2 tool to assess the methodo-logical quality of the *** utilized the bivariate random-effects model to calculate sensitivity,specificity,positive and negative test likelihood ratios(LR+and LR-),as well as the diagnostic odds ratio(DOR),and their 95%confidence *** conducted subgroup analyses based on urea dosing,time after urea administration,and assessment *** investigate a possible threshold effect,we conducted Spearman correlation analysis,and we generated summary receiver operating characteristic(SROC)curves to assess ***,we visually inspected a funnel plot and used Egger’s test to evaluate publication *** both as reliable diagnostic tools in clinical *** In summary,our study has demonstrated that ^(13)C-UBT has been found to outperform the ^(14)C-UBT,making it the preferred diagnostic ***,our results emphasize the significance of carefully considering urea dosage,assessment timing,and measurement techniques for both tests to enh

关键词： Helicobacter pylori Urea breath test Diagnosis Diagnostic test accuracy Meta-analysis

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In Silico and in Vitro Analysis of Pyrazolone Derivatives against Zika Virus and Identification of Potential NS5 Methyltransferase Inhibitors by Molecular Docking

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Journal of Biosciences and Medicines 2024年第7期12卷 214-229页

作者： Luciene Soares silva Tiago Soares Barbosa Maria Leonisa Sanchez-Nuñez Aldenise Mont Serrat Rosa da silva Vitor Won-Held Rabelo Leonardo dos Santos Corrêa Amorim Leonardo Alves Miceli Percilene Fazolin Vegi Alice Bernardino Helena carla Castro Izabel Christina Nunes de Palmer Paixão Science and Biotechnology Graduate Program Department of Cellular and Molecular Biology Institute of Biology Fluminense Federal University Niteri Brazil Science and Biotechnology Graduate Program Department of Cellular and Molecular Biology Institute of Biology Fluminense Federal University Niterói Brazil Laboratory of Antibiotics Biochemistry Teaching and Molecular Modeling Institute of Biology Fluminense Federal University Niterói Brazil Laboratory of Organic Chemistry at the Institute of Chemistry Institute of Biology Fluminense Federal University Niterói Brazil

Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complications. Although many efforts have been made to control ZIKV infection, approved vaccines or antiviral drugs are still lacking. Consequently, the development of new effective anti-ZIKV agents is urgently needed. In this context, we investigated the antiviral potential of pyrazolone derivatives against ZIKV replication using in silico and in vitro methods. The four pyrazolone derivatives evaluated (1a, 1b, 1c, and 1d) inhibited over 50% of ZIKV replication with low cytotoxicity. Among them, compound 1b exhibited the most potent activity (EC50 = 4.3 μM) and the highest selectivity (SI = 342). Mechanism of action studies indicated that these compounds act at early stages of virus replication, and compound 1b can also directly inactivate ZIKV particles. Molecular docking studies suggested that these compounds can bind to and block the activity of ZIKV NS5 methyltransferase. Finally, pharmacokinetic and toxicological predictions have reinforced the safety and drug-like profiles of these derivatives. In conclusion, the pyrazolone scaffold proved to be valuable for anti-ZIKV drug development, and the derivatives studied deserve further investigation.

关键词： Zika Pyrazolone NS5 Methyltransferase Antivirals

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A biophysical perspective on the unexplored mechanisms driving Parkinson’s disease by amphetamine-like stimulants

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Neural Regeneration Research 2021年第11期16卷 2213-2214页

作者： carla Ferreira joana Couceiro Sandra Tenreiro Alexandre Quintas Molecular Pathology and Forensic Biochemistry Laboratory Centro de Investigação Interdisciplinar Egas MonizP-2825-084 CaparicaPortugal Laboratório de Ciências Forenses e Psicológicas Egas Moniz Campus Universitário–Quinta da GranjaMonte de CaparicaP-2825-084 CaparicaPortugal Faculty of Medicine of Porto University Al.Prof.Hernâni MonteiroP-4200–319 PortoPortugal iNOVA4Health CEDOCNOVA Medical SchoolNMSUniversidade Nova de Lisboa1169-056 LisboaPortugal

Epidemiological studies have reported an increased risk of Parkinson’s disease(PD)development in amphetamine-type stimulant users during their lifetime(Garwood et al.,2006;Rumpf et al.,2017).Protein inclusions mainly composed of misfolded and aggregatedα-synuclein are the pathological hallmark of PD and other disorders known as *** studies present evidence that amphetamine upregulatesα-synuclein synthesis in substantia *** increment ofα-synuclein levels promotes its aggregation and amyloid fibril formation,increasing reactive oxygen species(ROS),and consequently dopamine oxidation(Wang and Witt,2014),known to be toxic for dopaminergic neurons involved in motor function and limbicmotor *** the years,these damaged cells lose their functionality and may die precociously,depleting the reserve of neural cells necessary for the normal neurological function which contributes to the onset of PD,when a critical number of cells are lost(Garwood et al.,2006).Therefore,the use of amphetamine-type stimulants may be a trigger event in the development of PD and parkinsonism,in conjugation to other risk factors that a given individual may *** the evidence,a previous study suggests that there is not enough data to corroborate the loss of dopamine neurons due to human amphetamine-type stimulant exposure,and consequently its implication in the PD development(Kish et al.,2017).

关键词： driving increment lifetime

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Antioxidant and antitumor potential of wild and IMT-Acultivated Osmundea pinnatifida

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Journal of Oceanology and Limnology 2019年第3期37卷 825-835页

作者： silva J.Paulo ALVES Celso PINTEUS Susete silva joana VALADO Ana PEDROSA Rui PEREIRA Leonel UCIBIO-REQUIMTE Department of ChemistryFaculty of Sciences and TechnologyUniversidade NOVA de LisboaCaparica 2829-516Portugal MARE-Marine and Environmental Sciences Centre School of Tourism and Maritime TechnologyPolytechnic Institute of LeiriaPeniche 2520-641Portugal Instituto Politécnico de Coimbra ESTESC-Coimbra Health SchoolBiomedical Sciences LaboratoryR.5 de OutubroS.Martinho do BispoAp.7006Coimbra 3046-854Portugal Centre of Pharmacology and Chemical Biopathology Faculty of MedicineUniversity of PortoPorto 4200-319Portugal MARE-Marine and Environmental Sciences Centre Department of Life SciencesFaculty of Sciences and TechnologyUniversity of CoimbraCoimbra 3000-456Portugal

Osmundea pinnatifida is a red edible seaweed known as pepper *** was cultivated in the farm of ALGAplus(ílhavo,Portugal).This farm is integrated with a seabream and seabass commercial aquaculture and uses the nutrient-enriched water resultant from the fish production as its cultivation medium in the integrated multi-trophic aquaculture(IMTA)*** and IMTA-cultivated samples of *** da were screened for antioxidant and antitumor *** antioxidant capacity of solvent extracts from wild and IMTA cultivated samples was assessed in two methods(2,2-diphenyl-1-picrylhydrazyl(DPPH)and oxygen radical absorbance capacity(ORAC)),and their total phenolic contents(TPC)were *** activity was evaluated in three different tumor cell lines(HepG-2,MCF-7,and SH-SY5Y)through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)*** the solvents used for extraction,dichloromethane was the most eff ective to extract phenolic compounds and presented higher ORAC.A significant correlation was found between TPC and ORAC,which was also sustained by the principal components analysis(PCA).Dichloromethane extracts induced a cytostatic eff ect on MCF-7 cells and showed weak cytotoxicity to SH-SY5Y cells and weak impact on cell ***,there were no statistically signifi cant differences in the biological activities shown by the wild and IMTA-cultivated ***,*** can be obtained in an economical and environmentally sustainable way through IMTA,maintaining bioactive properties in a high potential for further nutraceutical purposes.

关键词： edible seaweed bioactive compounds polyphenols cytotoxic activity antiproliferative activity

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

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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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