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

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

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Exercise stress echocardiography:Where are we now?

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World journal of Cardiology 2022年第2期14卷 64-82页

作者： Carlos Alberto Cotrim Hugo Café Isabel joão nuno Cotrim jorge Guardado Pedro Cordeiro Hortense Cotrim Luis Baquero Heart Center Hospital da Cruz Vermelha PortuguesaLisboa 1549-008Portugal Faculdade de Medicina Algarve UniversityFaro 8005-139Portugal Department of Cardiology Garcia de Orta HospitalAlmada 2805-267Portugal Department of Medicine Garcia de Orta HospitalAlmada 2805-267Portugal Cardiovascular Unit UCARDIOCentro ClinicoRiachos 2350-325Portugal Department of Cardiology Hospital Particular do AlgarveFaro 8005-226Portugal

Exercise stress echocardiography(ESE)is a widely used diagnostic test in cardiology *** is mainly used to study patients with coronary artery disease;however,it has increasingly been used in other clinical scenarios including valve pathology,congenital heart disease,hypertrophic and dilated cardiomyopathies,athlete evaluations,diastolic function evaluation,and pulmonary circulation *** our laboratories,we use an established methodology in which cardiac function is evaluated while exercising on a *** completing the exercise regimen,patients remain in a standing position or lie down on the left lateral decubitus,depending on the clinical questions to be answered for further *** method increases the quality and quantity of information ***,we present the various methods of exercise stress echocardiography and our experience in many clinical arenas in *** also present alternatives to ESE that may be used and their advantages and *** review recent advances in ESE and future directions for this established method in the study of cardiac patients and underline the advantage of using a diagnostic tool that is radiation-free.

关键词： Exercise stress echocardiography Coronary artery disease Valve disease Athletes Intraventricular gradients Children

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Multi-Project in an Integrated BIM Model: Clash Detection and Construction Planning

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journal of Software Engineering and Applications 2022年第10期15卷 345-358页

作者： Alcínia Zita Sampaio nuno R. gomes Augusto M. gomes Alberto Sanchez-Lite Department of Civil Engineering University of Lisbon Lisbon Portugal CERIS—Civil Engineering Research and Innovation for Sustainability IST Lisbon Portugal Department of Mechanical Engineering School of Industrial Engineering Universidad de Valladolid Valladolid Spain

The Building Information Modelling (BIM) methodology has been adopted in the construction industry, supporting the development of projects. Its implementation has improved the collaboration and integration in the design context, increasing the accuracy of the project preparation and the decreasing additional costs and delays of the construction work. The main objective of the present research is to provide an overview of the state of the art of BIM applications, namely, concerning the construction planning. For that, the generation of a BIM 3D model, involving the disciplines of architecture, structures and water supply system was performed. After, over the model a conflict analysis was applied, in order to verify the consistency of all the disciplines, when linked together. In order to obtain a visual simulation of the construction process, the correspondent 4D BIM model was also generated. Along the development of the study, distinct BIM software was applied over a case study. The main remarks of the capacities of the software, as well as the benefits and limitations verified were identified.

关键词： BIM Planning Construction Conflict Analysis 4D Model Visual Simulation

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Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats

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Asian journal of Andrology 2012年第4期14卷 635-642页

作者： Ines Tomada nuno Tomada Henrique Almeida Delminda Neves Department of Experimental Biology Faculty of MedicineUniversidade do Porto--Alameda ProfHernmai MonteiroPorto 4200-319Portugal Instituto de Biologia Molecular e Celular(IBMC) Universidade do Porto--Rua do Campo Alegre 823Porto 4150-180Portugal Department of Urology Centro Hospital S.JoaoEPE-Alameda ProfessorHernmani MonteiroPorto 4200-319Portugal

The purpose of the current study was to evaluate the effect of a high-fat （HF） diet, energy restriction and exercise on the expression of vascular endothelial growth factor （VEGF）, angiopoietin （Ang） I and 2, and their receptors in rat corpus cavernosum （CC）. Male Wistar rats were fed adlibitum with an H F diet for 8 or 16 weeks. After 8 weeks of the H F diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays （VEGF, VEGF receptor （VEGFR） I and 2, Angl, Ang2 and Tie2） and semiquantification of VEGF, VEGFR 1, VEGFR2, Angl, Ang2, Tie2, endothelial nitric oxide synthase （eNOS） and Aktlphospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol （HDL-c） levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.

关键词： angiopoietins corpus cavernosum endothelial dysfunction energy restriction exercise high-fat diet VEGF

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Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H pylori adhesion to gastric epithelial cells

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World journal of Gastroenterology 2008年第9期14卷 1411-1414页

作者： Natália R Costa nuno Mendes nuno T Marcos Celso A Reis Thomas Caffrey Michael A Hollingsworth Filipe Santos-Silva Institute of Molecular Pathology and Immunology University of PortoPorto 4200-465Portugal Institute of Molecular Pathology and Immunology University of Porto Porto 4200-465Portugal Medical Faculty University of Porto Porto 4200-465Portugal Eppley Institute for Research in Cancer and Allied Diseases University of Nebraska Medical CenterOmaha 68198-6805United States Institute of Molecular Pathology and Immunology University of PortoPorto 4200-465Portugal

AIM:To evaluate the influence of MUC1 mucin variable number of tandem repeats (VNTR) variability on H pylori adhesion to gastric cells. METHODS: Enzyme linked immunosorbent assay (ELISA)-based adhesion assays were performed to measure the adhesion of different H pylori strains (HP26695 and HPTx30a) to gastric carcinoma cell lines (GP202 and MKN45) and GP202 clones expressing recombinant MUC1 with different VNTR lengths. RESULTS: Evaluation of adhesion results shows that H pylori pathogenic strain HP26695 has a significantly higher (P < 0.05) adhesion to all the cell lines and clones tested, when compared to the non-pathogenic strain HPTx30a. Bacteria showed a significantly higher (P < 0.05) adhesion to the GP202 cell line, when compared to the MKN45 cell line. Furthermore, both strains showed a significantly higher (P < 0.05) adhesion to GP202 clones with larger MUC1 VNTR domains. CONCLUSION: This work shows that MUC1 mucin variability conditions H pylori binding to gastric cells. The extent of bacterial adhesion depends on the size of theMUC1 VNTR domain. The adhesion is further dependent on bacterial pathogenicity and the gastric cell line. MUC1 mucin variability may contribute to determine H pylori colonization of the gastric mucosa.

关键词： Hpylori MUC1 Variable number of tandem repeats Polymorphism Adhesion Mucin Gastric Infection

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COVID-19 pandemic and evolution of telemedicine to TeleIME

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Forensic Sciences Research 2021年第2期6卷 183-186页

作者： Mohammed Ranavaya Duarte nuno Vieira Division of Occupational Environmental and Disability MedicineJoan C.Edwards School of MedicineMarshall UniversityHuntingtonWVUSA Faculty of Medicine University of CoimbraCoimbraPortugal Institute of Legal Medicine and Institute of Bioethics CoimbraPortugal

The COVID-19 pandemic has been a life altering expe-rience that very few could have *** these unprecedented and uncertain times,with the majority of the world in some type of lockdown and travel restrictions in most places,medicine like many other fields of work has adapted to this challenging new *** particular the medical field has encouraged telemedicine and many patient visits have gone virtual.

关键词： ed. travel adapted

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The effects of low-volume combined training on health-related physical fitness outcomes in active young adults: A controlled clinical trial

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Sports Medicine and Health Science 2023年第1期5卷 74-80页

作者： Ricardo Martins nuno Loureiro Department of Arts Humanities and SportsSchool of EducationPolytechnic Institute of BejaLaboratory of Physical Activity and HealthBejaPortugal

The effects of combined training(CT)on improving general health are well known,however,few studies have investigated the effects of low-volume ***,the aim of this study is to investigate the effects of 6 weeks of lowvolume CT on body composition,handgrip strength(HGS),cardiorespiratory fitness(CRF)and affective response(AR)to *** healthy,active young adult man(meanSD,[20.061.66]years;[22.232.76]kg/m2)performed either a low-volume CT(EG,n?9),or maintained a normal life(CG,n?9).The CT was composed of three resistance exercises followed by a high intensity-interval training(HIIT)on cycle ergometer performed twice a *** measures of the body composition,HGS,maximal oxygen consumption(V_O2max)and AR to exercise were taken at baseline and after training for ***,an ANOVA test of repeated measures and t-test paired samples were used with a p*** results showed that EG improved HGS(pre:[45.6711.84]kg ***:[52.4411.90]kg,p0.05),nevertheless the feeling scale was positive in all weeks and without significant differences between them(p>0.05).Lastly,for active young adults,the low-volume CT improved HGS,CRF and had a positive outcome in AR,with less volume and time spent than traditional exercise recommendations.

关键词： Exercise Concurrent training Handgrip strength Cardiorespiratory fitness Affective response Untrained

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Ultrashort pulse capability at the L2I high intensity laser facility

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High Power Laser Science and Engineering 2017年第1期5卷 7-11页

作者： Gonqalo Figueira joana Alves joao M.Dias Marta Fajardo nuno gomes Victor Hariton Tayyab Imran Celso P.joao Jayanath Koliyadu Swen Kunzel Nelson C.Lopes Hugo Pires Filipe Ruao Gareth Williams GoLP/Instituto de Plasmas e Fusao Nuclear lnstituto Superior TecnieoUniversidade de LisboaLisbonPortugal Faculdade de Ciências e Tecnologia Universidade Nova de LisboaCaparicaPortugal Department of Physics&Astronomy College of ScienceKing Saud UniversityRiyadhSaudi Arabia

The Laboratory for Intense Lasers(L2I) is a research centre in optics and lasers dedicated to experimental research in high intensity laser science and technology and laser plasma interaction. Currently the laboratory is undergoing an upgrade with the goal of increasing the versatility of the laser systems available to the users, as well as increasing the pulse repetition rate. In this paper we review the current status of the laser research and development programme of this facility, namely the upgraded capability and the recent progress towards the installation of an ultrashort, diode-pumped OPCPA laser system.

关键词： diode-pumped solid-state laser and applications femtosecond laser and applications frequency conversion laser amplifiers nonlinear optics

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Lymphocyte subsets in alcoholic liver disease

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World journal of Hepatology 2013年第2期5卷 46-55页

作者： Luís Costa Matos Paulo Batista nuno Monteiro joo Ribeiro Maria A Cipriano Pedro Henriques Fernando Giro Armando Carvalho Faculty of Medicine of the University of Coimbra 3004-504 CoimbraPortugal Centro Hospitalar Tondela Viseu E.P.E3504-509 ViseuPortugal Department of Anatomopathology University of Coimbra Hospital3004-504 CoimbraPortugal

AIM:To compare lymphocyte subsets between healthy controls and alcoholics with liver ***:The patient cohort for this study included individuals who were suspected to have alcoholic liver disease(ALD) and who had undergone liver biopsy(for disease grading and staging,doubts about diagnosis,or concurrent liver disease;n = 56).Normal controls included patients who were admitted for elective cholecystectomy due to non-complicated gallstones(n = 27).Formalin-fixed,paraffin-embedded liver biopsy specimens were sectioned and stained with hematoxylin and eosin and Perls' Prussian *** non-alcoholic steatohepatitis score was used to assess markers of *** population subsets were determined by flow cytometry.T lymphocytes were identified(CD3+),and then further subdivided into CD4+ or CD8+ populations.B lymphocytes(CD19+) and natural killer(NK) cell numbers were also *** addition to assessing lymphocyte subpopulation differences between ALD patients and controls,we also compared subsets of alcoholic patients without cirrhosis or abstinent cirrhotic patients to normal ***:The patient cohort primarily consisted of older *** alcoholism was present in 66.1%.Reported average daily alcohol intake was 164.9 g and the average lifetime cumulative intake was 2211.6 *** was present in 39.3% of the patients and 66.1% had significant fibrosis(perisinusoidal and portal/periportal fibrosis,bridging fibrosis,or cirrhosis) in their liver *** average Mayo end-stage liver disease score was *** hereditary hemochromatosis genotypes were *** patients(n = 56) presented with significant lymphopenia(1.5 × 109/L ± 0.5 × 109/L vs 2.1 × 109/L ± 0.5 × 109/L,P < 0.0001),due to a decrease in all lymphocyte subpopulations,except for NK lymphocytes:CD3+(1013.0 ± 406.2/mm3 vs 1523.0 ± 364.6/mm3,P < 0.0001),CD4+(713.5 ± 284.7/mm3 vs 992.4 ± 274.7/mm3,P < 0.0001),CD8+(262.3 ± 140.4/mm3 vs 478.9 ± 164.6/mm3,P < 0.0001),and CD19+(120.6

关键词： Lymphocyte subsets Flow cytometry Alcoholism Alcoholic liver disease Liver fibrosis Liver biopsy HFE gene

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Stabilisation of estuarine sediments with an alkali-activated cement for deep soil mixing applications

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journal of Rock Mechanics and Geotechnical Engineering 2024年第4期16卷 1398-1410页

作者： Claver Pinheiro Sara Rios António Viana da Fonseca nuno Cristelo Centre of Physics of Minho and Porto Universities (CF-UM-UP) Azurém CampusUniversity of MinhoGuimarães4800-058Portugal CONSTRUCT-GEO Faculty of EngineeringUniversity of PortoRua Dr.Roberto FriasPortos/n 4200-465Portugal CQ-VR School of Science and TechnologyUniversity of Trás-os-Montes e Alto DouroVila Real5000-801Portugal

In this work,an alternative alkali-activated cement(AAC)made of ladle slag precursor mixed with sodium hydroxide and sodium silicate has been developed to enhance the bearing capacity of estuarine soils in coastal conditions via deep soil mixing(DSM).The AAC was optimized to use a low reactivity precursor(ladle slag)and to deal with a contaminated high-water content natural sediment cured under *** material performance was analysed by comparison to a mixture made with Portland cement and cured in the same *** and unconfined compressive strength tests as well as seismic waves measurements after 3-,7-,14-and 28-d curing were performed to obtain a relationship between elastic stiffness and strength with curing time for both ***,the AAC mix demonstrated superior strength results,exhibiting almost double flexural and compressive strengths after 28 d compared to the Portland cement *** AAC mix also showed a higher rate of stiffness increase than the Portland cement mix,which has a higher initial stiffness at young ages but lower stiffness *** analysis confirmed that the proposed AAC could effectively immobilise any contaminants from soil or *** effect of curing under stress was analysed in triaxial compression tests and found to be insignificant,indicating that laboratory data obtained without stress curing can represent the material's behaviour in a DSM column,which will cure under the weight of the column.

关键词： Alkaline-activation Steel slag Submerged curing Seismic wave measurements Leachate analysis Curing under stress

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