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Indirect printing of hierarchical patient-specific scaffolds for meniscus tissue engineering

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Bio-Design and Manufacturing 2019年第4期2卷 225-241页

作者： Joao BCosta joana silva-correia Sandra Pina Alain da silva Morais Sílvia Vieira Hélder Pereira Joao Espregueira-Mendes Rui LReis Joaquim M.Oliveira B′s Research Group I3Bs-Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkZona Industrial da Gandra4805-017 Barco GmrPortugal ICVS/3B’s-PT Government Associate Laboratory Braga/GuimaraesPortugal The Discoveries Centre for Regenerative and Precision Medicine Headquarters at University of MinhoAvepark4805-017 BarcoGuimar'sPortugal Ripoll y De Prado Sports Clinic:Murcia-Madrid FIFA Medical Centre of Excellence MurciaSpain Orthopedic Department Centro Hospitalar Póvoa de Varzim Vila do CondePortugal Clínica do Dragao Espregueira-Mendes Sports CentreFIFA Medical Centre of ExcellencePortoPortugal Dom Henrique Research Centre PortoPortugal Orthopedic Department University of MinhoBragaPortugal

The complex meniscus tissue plays a critical role in the knee. The high susceptibility to injury has led to an intense pursuit for better tissue engineering regenerative strategies, where scaffolds play a major role. In this study, indirect printed hierarchical multilayered sca ffolds composed by a silk fibroin (SF) upper layer and an 80/20 (w/w) ratio of SF/ionic-doped β-tricalcium phosphate (TCP) bottom layer were developed. Furthermore, a comparative analysis between two types of sca ffolds pro- duced using di fferent SF concentrations, i.e., 8% (w/v) (Hi8) and 16% (w/v) (Hi16) was performed. In terms of architecture and morphology, the produced sca ffolds presented homogeneous porosity in both layers and no di fferences were observed when comparing both sca ffolds. A decrease in terms of mechanical performance of the sca ffolds was observed when SF concentration decreased from 16 to 8% (w/v). Hi16 revealed a static compressive modulus of 0.66 ± 0.05 MPa and dynamical mechanical properties ranging from 2.17 ± 0.25 to 3.19 ± 0.38 MPa. By its turn, Hi8 presented a compressive modulus of 0.27 ± 0.08 MPa and dynamical mechanical properties ranging from 1.03 ± 0.08 MPa to 1.56 ± 0.13 MPa. In vitro bioactivity studies showed formation of apatite crystals onto the surface of Hi8 and Hi16 bottom layers. Human meniscus cells (hMCs) and human primary osteoblasts were cultured separately onto the top layer (SF8 and SF16) and bottom layer (SF8/TCP and SF16/TCP) of the hierarchical sca ffolds Hi8 and Hi16, respectively. Both cell types showed good adhesion and proliferation as denoted by the live/dead staining, Alamar Blue assay and DNA quanti fication analysis. Subcutaneous implantation in mice revealed weak in flammation and sca ffold’s integrity. The hierarchical indirect printed SF sca ffolds can be promising candidate for meniscus TE sca ffolding applications due their suitable mechanical properties, good biological performance and possibility of being applied in a patie

关键词： Patient-specific Indirect printing Hierarchical Silk fibroin Enzymatic-cross-linking Meniscus

Diabetic peripheral neuropathy and neuromodulation techniques:a systematic review of progress and prospects

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Neural Regeneration Research 2025年第8期20卷 2218-2230页

作者： Rahul Mittal Keelin McKenna Grant Keith Evan McKenna joana R.N.Lemos Jeenu Mittal Khemraj Hirani Diabetes Research Institute University of Miami Miller School of MedicineMiamiFLUSA Department of Otolaryngology University of Miami Miller School of MedicineMiamiFLUSA Herbert Wertheim College of Medicine Florida International UniversityMiamiFLUSA School of Medicine and Public Health University of WisconsinMadisonWIUSA

Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this *** peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and *** aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this *** investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord *** systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral *** the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic *** these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

关键词： diabetes mellitus diabetic peripheral neuropathy neuromodulation neurostimulation therapy non-pharmacological treatment pain management

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

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

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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

Developing and validating a nestling photographic aging guide for cavity-nesting birds: an example with the European Bee-eater(Merops apiaster)

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Avian Research 2020年第1期11卷 57-64页

作者： joana S.Costa Afonso D.Rocha Ricardo A.correia Jose A.Alves Department of Biology&CESAM University of AveiroCampus Universitario de Santiago3810-193 AveiroPortugal Institute of Biological and Health Sciences(ICBS) Federal University of AlagoasMaceioALBrazil University of Iceland South Iceland Research CentreLindarbraut 4840 LaugarvatnIceland

Background: Accurate estimation of nestlings’ age is essential in avian demography studies as well as in population ecology and conservation. For example, it can be useful for synchronizing nest visits with events of particular interest, such as the age at which young can be safely ringed, or in choosing the best period to attain the most accurate calculation of laying or hatching ***: We constructed a photographic guide for aging European Bee-eaters(Merops apiaster) nestlings to 3-day age classes and evaluated the aging method by performing a validation exercise with several observers with no previous experience in aging bee-eater ***: The aging guide for bee-eater nestlings allowed estimating age to within 3 days with an average accuracy of 0.85. We found the optimal period for aging nestlings was between days 13-18(with accuracy between 0.94 and 0.99), during which the status of feather development was more easily distinguishable from the preceding and subsequent age classes. During the first 3 days after hatching, nestlings could also be aged with high accuracy(0.93). The small size of the nestling in relation to the eggs and the nestling’s inability to raise its head during these first days allowed for good discrimination from the subsequent age class. Between days 25 and 28, nestlings were correctly aged in only half of assignments(0.55 sensitivity) and nestlings belonging to class 7(days 7-9) were the least correctly identified(0.38 sensitivity). However, by visiting the nests at 12 days intervals it is possible to achieve the highest accuracy in age estimation with the smallest disturbance and logistic ***: This study highlighted how indirect methods and a simple protocol can be established and employed to quickly estimate nestling age in cases where handling nestlings is challenging or impossible, while minimizing disturbance in and around the nest.

关键词： Age estimation Chick development Feather growth Image guide Nest visit Plumage colour

A multi-integrated approach on toxicity effects of engineered TiO2 nanoparticles

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Frontiers of Environmental Science & Engineering 2015年第5期9卷 793-803页

作者： Ana PICADO Susana M. PAIXAO Liliana MOITA Luis silva Mario S. DINIZ joana LOURENCO Isabel PERES Luisa CASTRO Jose Brito correia joana PEREIRA Isabel FERREIRA Antonio Pedro Alves MATOS Pedro BARQUINHA Elsa MENDONCA LNEG-National Laboratory of Energy and Geology I.P. Lisbon 1649-038 Portugal REQUIMTE Chemistry Department Fine Chemistry and Biotechnology Center Faculty of Sciences and Technology New University of Lisbon Caparica 2829-516 Portugal IMAR-Ocean Institute Department of Sciences and Environmental Engineering Faculty of Sciences and Technology New University of Lisbon Caparica 2829-516 Portugal CENIMAT/I3N and Department of Materials Science Faculty of Sciences and Technology New University of Lisbon Caparica 2829-516 Portugal Pathological Anatomy Curry Cabml Hospital Lisbon 1069-166 Portugal CESAM Faculty of Sciences Lisbon University Lisbon 1749-016 Portugal

The new properties of engineered nanoparti- cles drive the need for new knowledge on the safety, fate, behavior and biologic effects of these particles on organisms and ecosystems. Titanium dioxide nanoparticles have been used extensively for a wide range of applica- tions, e.g, self-cleaning surface coatings, solar cells, water treatment agents, topical sunscreens. Within this scenario increased environmental exposure can be expected but data on the ecotoxicological evaluation ofnanoparticles are still scarce. The main purpose of this work was the evaluation of effects of TiO2 nanoparticles in several organisms, covering different trophic levels, using a battery of aquatic assays. Using fish as a vertebrate model organism tissue histological and ultrastructural observations and the stress enzyme activity were also studied. TiO2 nanoparticles （Aeroxide~ P25）, two phase composition ofanatase （65%） and rutile （35%） with an average particle size value of 27.64-11 nm were used. Results on the ECs0 for the tested aquatic organisms showed toxicity for the bacteria, the algae and the crustacean, being the algae the most sensitive tested organism. The aquatic plant Lemna minor showed no effect on growth. The fish Carassius auratus showed no effect on a 21 day survival test, though at a biochemical level the cytosolic Glutathione-S-Transferase total activity, in intestines, showed a general significant decrease （p〈0.05） after 14 days of exposure for all tested concentrations. The presence of TiO2 nanoparticles aggregates were observed in the intestine lumen but their internalization by intestine cells could not be confirmed.

关键词： ecotoxicity enzymatic analysis histology,transmission electron microscopy (TEM) TiO2-nanoparti-cles

The road to sustainable use and waste management of plastics in Portugal

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Frontiers of Environmental Science & Engineering 2022年第1期16卷 91-106页

作者： joana C.Prata Ana LPatrício silva Armando CDuarte Teresa Rocha-Santos Centre for Environmental and Marine Studies(CESAM)&Department of Chemistry University of Aveiro3810-193 AveiroPortugal Centre for Environmental and Marine Studies(CESAM)&Department of Biology University of Aveiro3810-193 AveiroPortugal

As a European Union(EU)member,Portugal must comply with reductions in plastic *** Portugal,the 330 items/100 m of beach litter,comprising up to 3.9 million pieces and of which 88%is plastic,is higher than the EU median(149 items/100 m)and must be reduced to 20 items/100 m(94%).Integrative measures are needed to reduce littering and improve plastics’use and disposal under the circular *** this 414 kt of plastic packaging waste,163 kt were declared plastic packaging,140 kt subjected to recycling,and 94 kt to energy *** current recycling rate of plastic packaging(34%)should be improved to reach EU recycling averages(42%)and goals and to provide widespread benefits,considering revenues of 167€/*** a net importer of waste,Portugal could benefit from the valorization of imported *** increased recycling,pyrolysis and gasification could provide short-term alternatives for producing value-added substances from plastic waste,such as hydrogen,consistent with the National Plan of Hydrogen and improving ongoing regulations on single-use *** manuscript provides an integrative view of plastics in Portugal,from use to disposal,providing specific recommendations under the circular economy.

关键词： Single-use plastics Plastic packaging Plastic waste Waste management Waste shipment Lightweight plastic bags

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

Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5404-5416页

作者： Catarina Macedo-silva Vera Miranda-Gonçalves Nuno Tiago Tavares Daniela Barros-silva joana Lencart João Lobo Ângelo Oliveira Margareta Pcorreia Lucia Altucci Carmen Jerónimo Cancer Biology&Epigenetics Group Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of Precision Medicine University of Campania“Luigi Vanvitelli”80138NaplesItaly Department of Pathology and Molecular Immunology ICBAS-School of Medicine&Biomedical SciencesUniversity of PortoR.Jorge de Viterbo Ferreira 2284050-313PortoPortugal Medical Physics Radiobiology and Radiation Protection Group-Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of Medical Physics Portuguese Oncology Institute of Porto4200-072PortoPortugal Department of Pathology Portuguese Oncology Institute of PortoPortoPortugal Department of Radiation Oncology Portuguese Oncology Institute of PortoPortoPortugal BIOGEM Molecular Biology and Genetics Research Institute83100AvellinoItaly IEOS Institute of Endocrinology and Oncology80100NaplesItaly

External beam radiotherapy(RT)is a leading first-line therapy for prostate cancer(PCa),and,in recent years,significant advances have been ***,RT resistance can arise and result in long-term recurrence or disease progression in the worst-case ***,making crucial the discovery of new targets for PCa ***,we generated a radioresistant PCa cell line,and found p53 to be highly expressed in radioresistant PCa cells,as well as in PCa patients with recurrent/disease progression submitted to *** dissection revealed that RT could promote p53 expression via epigenetic ***,a decrease of H3K27me3 occupancy at TP53 gene promoter,due to increased KDM6B activity,was observed in radioresistant PCa ***,p53 is essential for efficient DNA damage signaling response and cell recovery upon stress induction by prolonged fractionated ***,KDM6B inhibition by GSK-J4 significantly decreased p53 expression,consequently attenuating the radioresistant phenotype of PCa cells and hampering in vivo 3D tumor ***,this work contributes to improve the understanding of p53 as a mediator of signaling transduction in DNA damage repair,as well as the impact of epigenetic targeting for PCa radiosensitization.

关键词： TP53 damage cancer