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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

Intranasal delivery of nanostructured lipid carriers,solid lipid nanoparticles and nanoemulsions:A current overview of in vivo studies

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Acta Pharmaceutica Sinica B 2021年第4期11卷 925-940页

作者： Cláudia Pina Costa joao nuno Moreira joséManuel Sousa Lobo Ana Catarina silva UCIBIo/REQUIMTE MedtechLaboratory of Pharmaceutical TechnologyDepartment of Drug SciencesFaculty of PharmacyUniversity of PortoPorto 4050-313Portugal CNC-Center for Neuroscience and Cell Biology Center for Innovative Biomedicine and Biotechnology(CIBB)University of CoimbraFaculty of Medicine(Pólo I)Coimbra 3004-504Portugal UC-University of Coimbra CIBBFaculty of PharmacyPólo Das Ciências da SaúdeCoimbra 3000-548Portugal FP-ENAS(UFP Energy Environment and Health Research Unit)CEBIMED(Biomedical Research Centre)Faculty of Health SciencesUniversity Fernando PessoaPorto 4249-004Portugal

The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the *** the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising *** addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc *** review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain *** on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal *** results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried *** the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the *** systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.

关键词： Nose-to-brain delivery Intranasal administration Nanostructured lipid carriers NLC Solid lipid nanoparticles SLN Nanoemulsions In vivo studies Pharmacokinetic Pharmacodynamics

Publishing NextGEoSS data on the GEoSS Platform

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Big Earth Data 2023年第2期7卷 413-427页

作者： Roberto Roncella Enrico Boldrini Mattia Santoro Paolo Mazzetti joão Andrade nuno Catarino Stefano Nativi National Research Council of Italy Institute of Atmospheric Pollution ResearchDivision of FlorenceFlorenceItaly Deimos Engenharia Avenida Columbano BordaloPinheiroLisbonPortugal

This paper is the second of a series that describes some of the main dataset resources presently shared through the GEoSS Platform. The GEoSS Platform was created as the technological tool to implement interoperability among the Global Earth observation System of Systems (GEoSS);it is a brokering infrastructure that presently brokers more than 190 autonomous data catalogs and information systems. This paper is focused on the analysis of the NextGEoSS datasets describing the data publishing process from NextGEoSS to the GEoSS platform. In particular, both the administrative registration and the technical registration were taken into consideration. one of the most important data shared by the GEoSS Platform are the NextGEoSS datasets: the present study provides some insights in terms of GEoSS user searches for NextGEoSS data.

关键词： Earth observation GEoSS data interoperability data sharing data brokering services

Metal alginates for polyphenol delivery systems: Studies on crosslinking ions and easy-to-use patches for release of protective flavonoids in skin

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Bioactive Materials 2020年第3期5卷 447-457页

作者： joão silva Pavlo Vanat Dorinda Marques-da-silva joaquim Rui Rodrigues Ricardo Lagoa School of Technology and Management Polytechnic Institute of LeiriaPortugal Laboratório Associado LSRE-LCM School of Technology and ManagementPolytechnic Institute of LeiriaPortugal UCIBIo-Faculty of Science and Technology NOVA University of LisbonPortugal

Incorporation of bioactive natural compounds like polyphenols is an attractive approach for enhanced functionalities of *** particular flavonoids have important pharmacological activities,and controlled release systems may be instrumental to realize the full potential of these *** presents interesting attributes for dermal and other biomaterial applications,and studies were carried here to support the development of polyphenol-loaded alginate *** of capillary viscosity indicated that ionic medium is an effective strategy to modulate the polyelectrolyte effect and viscosity properties of *** gelation,considerable differences were observed between alginate gels produced with Ca^2+,Ba^2+,Cu^2+,Fe^2+,Fe^3+and Zn^2+as crosslinkers,especially concerning shrinkage and morphological *** assays with different polyphenols in the presence of alginate-gelling cations pointed to the choice of calcium,barium and zinc as safer ***-based films loaded with epicatechin were prepared and the kinetics of release of the flavonoid *** results with calcium,barium and zinc alginate matrices indicated that the release dynamics is dependent on film thicknesses,but also on the crosslinking metal *** these grounds,an alginate-based system of convenient use was devised,so that flavonoids can be easily loaded at simple point-of-care conditions before dermal *** epicatechin-loaded patch was tested on an ex-vivo skin model and demonstrated capacity to deliver therapeutically relevant concentrations on skin ***,the flavonoid released was not modified and retained full antioxidant *** alginate-based system proposed offers a multifunctional approach for flavonoid controllable delivery and protection of skin injured or under risk.

关键词： Topical drug delivery Intrinsic viscosity Biopolymer Epigallocatechin-gallate Antioxidant dressing

Chronological Age and Performance in Paralympic Powerlifters: Differences Between Sexes, Competition, and Weight Categories

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journal of Science in Sport and Exercise 2023年第1期5卷 53-61页

作者： joão Paulo Lopes-silva Dillon Richardson Emerson Franchini Applied Research Group Performance and Health CESMAC University CenterMaceióAlagoasBrazil International Paralympic Committee(IPC) BonnGermany Sport Department School of Physical Education and SportUniversity of Sao PauloSao PauloBrazil

Purpose We quantified the chronological age and performance of Paralympic powerlifters competing at the elite level in the World Championships(WC)and Paralympic Games(PG),and examined the age-related differences between sexes,weight categories,and competition *** This was a retrospective study involving 3107 athletes who took part in the last eight WC and six *** pow-erlifters were divided by sex,chronological age,weight category,and competition *** overall,males were older(33 years)and stronger(lifting 168 kg)than female(32 years and lifting 96 kg,respec-tively)para powerlifters(Powerlifters lifted heavier loads in the PG(174 and 103 kg,respectively)than in WC(163 and 93 kg,respectively)and medallists were younger(31 and 30 years for females and males,respectively)than non-medallists(33 and 32 years for females and males,respectively)(Powerlifters compet-ing in lighter categories were younger when compared to heavier categories(Poad was heavier compared to heavier competitors(Ponclusion our results show that medallists were younger(31 and 30 years)than non-medallists(33 and 32 years)for females and males,respectively.

关键词： Data analysis Para athletes Sports performance Gender

Best practices for electrochemical characterization of supercapacitors

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journal of Energy Chemistry 2023年第5期80卷 265-283,I0007页

作者： joão Pedro Aguiar dos Santos Fernando Cesar Rufino joǎo IYutaka ota Rodolfo CFernandes Rafael Vicentini Cesar JBPagan Leonardo Morais Da silva Hudson Zanin Brazilian Renewable Energies Center for Innovation on New EnergiesSchool of Electrical and Computer EngineeringUniversity of CampinasSP 13083-852Brazil School of Electrical and Computer Engineering University of CampinasSP 13083-852Brazil Department of Chemistry Laboratory of Fundamental and Applied ElectrochemistryFederal University of Jequitinhonha e Mucuri's ValleyRodovia MGT 367km 5835000Alto da Jacuba39100-000 DiamantinaMGBrazil

We discuss here essential aspects of the experimental supercapacitors characterization by a series of well-known electrochemical *** are motivated by a considerable number of publications that misreport procedures and *** often conceal or neglect essential information about the electrochemical analytical apparatus used and its *** lack of such information may lead researchers,especially inexperienced ones,to misunderstand the procedures and ***,the misled electrochemical equipment configuration favors misinterpretation of data and low reproducibility *** paper aims to highlight these issues and clarify *** explain fundamental concepts of some electrochemical analytical methods,such as cyclic voltammetry,galvanostatic charge-discharge,single potential step chronoamperometry,and electrochemical impedance spectroscopy,focusing on the supercapacitor *** configurations of electrical parameters are presented and discussed to highlight the effects of incorrect setup and uncover misleading *** discuss how the electrochemical setup and data analyses matter in reliable data results for the supercapacitor.

关键词： Supercapacitor Electrochemical instrumentation Electrochemical methods Electrochemistry

Anal canal gastrointestinal stromal tumors:Case report and literature review

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World journal of Gastroenterology 2014年第1期20卷 319-322页

作者： nuno Carvalho Diogo Albergaria Rui Lebre joo Giria Vitor Fernandes Helena Vidal Maria josé Brito Department of General Surgery Garcia de Orta Hospital2801-951 AlmadaPortugal Department of Gastroenterology Garcia de Orta Hospital2801-951 AlmadaPortugal Department of Radiology Garcia de Orta Hospital2801-951 AlmadaPortugal Department of Pathology Garcia de Orta Hospital2801-951 AlmadaPortugal

Gastrointestinal stromal tumors (GIST) are an uncommon group of tumors of mesenchymal origin. GIST of the anal canal is extremely rare. At present, only 10 cases of c-kit positive anal GIST have been reported in the literature. There is no widely accepted treatment approach for this neoplasia. Literature is sparse on imaging evaluation of anal canal GIST, usually described as a lesion in the intersphincteric space. We describe the case of a 73-year-old man with a mass in the anal canal, and no other symptoms. Endoanal ultrasound and magnetic resonance imaging showed a well circumscribed solid nodule in the intersphincteric space. The patient was treated by local excision. Gross pathological examination showed a 7 cm × 3.5 cm × 3 cm mass, and histological examination showed a proliferation of spindle cells, with prominent nuclear palisading. The mitotic count was of 12 mitoses/50 HPF. The tumor was positive for KIT protein, CD34 and vimentin in the majority of cells, and negative for desmin and S100. A diagnosis of GIST, with high risk aggressive behavior was made. An abdomino-perineal resection was discussed, but refused. The follow-up included clinical evaluation and anal ultrasound. After 5 years the patient is well, with maintained continence and no evidence of local recurrence.

关键词： Gastrointestinal stromal tumors Anal canal Endoanal ultrasound Magnetic resonance imaging C-Kit receptor Local excision

Determination of critical state line(CSL)for silty-sandy iron ore tailings subjected to low-high confining pressures

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journal of Rock Mechanics and Geotechnical Engineering 2024年第5期16卷 1684-1695页

作者： Nilo Cesar Consoli joão Vítor de Azambuja Carvalho Alexia Cindy Wagner Hugo Carlos Scheuermann Filho Inácio Carvalho Pedro Pazzoto Cacciari joão Paulo de Sousa silva Civil Engineering Universidade Federal do Rio Grande do SulPorto AlegreRS90035-190Brazil Exploration and Mineral Projects-Mineral Development Centre VALE S.A.Santa LuziaMG33040-900Brazil Department of Civil Geological and Mining EngineeringPolytechnique MontrealQuebecH3C 3A7Canada

The disposal of filtered tailings in high dry stacks can induce particle breakage,changing the material's behaviour during the structure's *** grading changes influence material properties at the critical state,and this is not mature for intermediate artificial soils(tailings)in a broad range of confining *** this paper,it aims to describe the behaviour of iron ore tailings in a spectrum of confining pressures broader than the reported in previous studies.A series of consolidated drained(CD)triaxial tests was carried out with confining pressures ranging from 0.075 MPa to 120 *** results show that the amount of breakage plays an essential role in the response of iron ore *** existence of curved critical state line(CSL)in both specific volume(ν)-logarithm of mean effective stress(p′)and deviatoric stress(q)-mean effective stress(p′)planes,and different responses in the deviatoric stress-axial strain-volumetric strain curves were *** inverse S-shaped equation was proposed to represent the silty-sandy tailings'behaviour up to high pressures onν-lnp′*** proposed equation provides a basis for enhancing constitutive models and considers the evolution of the grading up to severe loading *** adjustment considered three regions with different responses associated with particle breakage at different pressure levels.

关键词： Tailings Iron ore tailings dry stacking Silty-sandy material Critical state soil mechanics High confining pressures Particle breakage

Scalable fabrication,compartmentalization and applications of living microtissues

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Bioactive Materials 2023年第1期19卷 392-405页

作者： Maik Schot nuno Araújo-Gomes Bas van Loo Tom Kamperman Jeroen Leijten Department of Developmental Bioengineering Faculty of Science and TechnologyTechnical Medical CentreUniversity of TwenteDrienerlolaan 57522NBEnschedethe Netherlands

Living microtissues are used in a multitude of applications as they more closely resemble native tissue physiology,as compared to 2D *** are typically composed of a combination of cells and materials in varying combinations,which are dictated by the applications’design *** applications range wide,from fundamental biological research such as differentiation studies to industrial applications such as cruelty-free meat ***,their translation to industrial and clinical settings has been hindered due to the lack of scalability of microtissue production *** microfluidic processes provide an opportunity to overcome this limitation as they offer higher throughput production rates as compared to traditional batch techniques,while maintaining reproducible control over microtissue composition and *** this review,we provide a comprehensive overview of the current approaches to engineer microtissues with a focus on the advantages of,and need for,the use of continuous processes to produce microtissues in large ***,an outlook is provided that outlines the required developments to enable large-scale microtissue fabrication using continuous processes.

关键词： Tissue engineering Micromaterials Microfluidics Upscaling Clinical translation Industrial translation