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Efflux Pumps Modulation in Colorectal Adenocarcinoma Cell Lines: The Role of Nuclear Medicine

Journal of Cancer Therapy 2011年第3期2卷 408-417页

作者： joao casalta-lopes Ana Margarida Abrantes Mafalda Laranjo Joana Rio Ana Cristina Goncalves Barbara Oliveiros Ana Bela Sarmento-Ribeiro Maria Filomena Botelho Biophysics Unit IBILIFaculty of MedicineUniversity of CoimbraCoimbraPortugal Centre of Investigation on Cancer Envi-ronmentGenetics and OncobiologyFaculty of MedicineUniversity of CoimbraCoimbraPortugal Institute of Nuclear Sciences Applied to Health University of CoimbraCoimbraPortugal Applied Molecular Biology Unit Faculty of MedicineUniversity of CoimbraCoimbraPortugal.

Introduction: Multidrug resistance (MDR) is one of the major problems of chemotherapy. Overexpression of efflux pumps, such as P-glycoprotein (Pgp), multiple resistance-related protein 1 (MRP-1) and lung resistance protein (LRP) can lead to MDR. Verapamil and L-buthionine-sulfoximine (BSO) are two modulators of these proteins. This study aims to compare 99mTc-Sestamibi transport kinetics in human colorectal adenocarcinoma cell lines, in the presence and absence of the MDR modulators verapamil and BSO. Material and Methods: MDR proteins expression was evaluated in sensitive (WiDr) and resistant (LS1034) human colorectal adenocarcinoma cell lines. Intracellular and plasma membrane Pgp and MRP1, and LRP expression was analyzed by flow-cytometry and western blot. Cellular transport kinetics was assessed using 99mTc-Sestamibi. MDR modulation was evaluated though retention studies in resistant cells after incubation with the modulators. Results: Pgp expression was significantly higher (p≤0.001) in resistant cells. These results were confirmed by western blot analysis. 99mTc-Sestamibi uptake and retention percentage were significantly higher (p99mTc-Sestamibi, there were differences among the MDR modulators used (p99mTc-Sestamibi could indicate MDR phenotype in colorectal adenocarcinoma cells. As the modulators used showed a reversion of the retention profile only for the first minutes, their administration should occur immediately before the administration of cytotoxic drugs.

关键词： Multidrug Resistance P-Glycoprotein Multidrug Resistance-Associated Protein 1 Major Vault Protein

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Comparative effects of insecticides with different mechanisms of action on Chrysoperla externa （Neuroptera＂ Chrysopidae）＂ Lethal, sublethal and dose-response effects

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Insect Science 2013年第6期20卷 743-752页

作者： Moises joao Zotti Anderson Dionel Grutzmacher Isac Heres lopes Guy Smagghe UGent-Crop Protection Ghent Oost-Vlaanderen Belgium UFPel - Phytosanitary Pelotas RS Brazil

The comprehensive knowledge that the delayed systemic and reproduction side effects can be even more deleterious than acute toxicity, has caused a shift in focus toward sublethal effects assessment on physiology and behavior of beneficial insects. In this study, we assessed the risks posed by some insecticides with different mode of action through lethal and delayed systemic sublethal effects on the pupation, adult emergence, and repro- duction of the chrysopid Chrysoperla externa （Hagen, 1861; Neuroptera： Chrysopidae）, an important predator in pest biological control. The maximum field recommended dose （MFRD） and twice （2xMFRD） for chlorantraniliprole, tebufenozide, and pyriproxyfen were harmless to C. externa. In contrast, all the tested chitin synthesis inhibitors （CSIs） were highly detrimental to the predator, despite of their lack of acute lethal toxicity. There- fore, the safety assumed by using IGRs toward beneficial insects is not valid for chrysopids. Dose-response data showed that although all CSIs have a similar mechanism of action, the relative extent of toxicity may differ （novaluron 〉 lufenuron 〉 teflubenzuron）. For CSIs, the delayed systemic effects became obvious at adult emergence, where the predicted no observable effect dose （NOED） was 1/2 048 of the MFRD for novaluron （0.085 ng/insect）, and 1/256 of the MFRD for both lufenuron （0.25 ng/insect） and teflubenzuron （0.6 ng/insect）. Finally, this work emphasized the significance of performing toxicity risk assessments with an adequate posttreatment period to avoid underestimating the toxicities of insecticides, as the acute lethal toxicity assays may not provide accurate information regarding the long-range effects of hazardous compounds.

关键词： Chrysoperla externa dose-response effects ecotoxicology IGRs insecti-cide risk assessment topical application

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Induced pluripotent stem cells, a giant leap for mankind therapeutic applications

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World Journal of Stem Cells 2019年第7期11卷 421-430页

作者： JoséBraganca joao Andrélopes Leonardo Mendes-Silva joao Miguel Almeida Santos Department of Biomedical Sciences and Medicine University of AlgarveFaro 8005-139Portugal Centre for Biomedical Research(CBMR) University of AlgarveFaro 8005-139Portugal

Induced pluripotent stem cells(iPSC)technology has propelled the field of stem cells biology,providing new cells to explore the molecular mechanisms of pluripotency,cancer biology and aging.A major advantage of human iPSC,compared to the pluripotent embryonic stem cells,is that they can be generated from virtually any embryonic or adult somatic cell type without destruction of human *** addition,iPSC can be generated from somatic cells harvested from normal individuals or patients,and used as a cellular tool to unravel mechanisms of human development and to model diseases in a manner not possible *** these fundamental aspects of human biology and physiology that are revealed using iPSC or iPSC-derived cells,these cells hold an immense potential for cell-based therapies,and for the discovery of new or personalized pharmacological treatments for many ***,we review some of the current challenges and concerns about iPSC *** introduce the potential held by iPSC for research and development of novel health-related *** briefly present the efforts made by the scientific and clinical communities to create the necessary guidelines and regulations to achieve the highest quality standards in the procedures for iPSC generation,characterization and long-term ***,we present some of the audacious and pioneer clinical trials in progress with iPSC-derived cells.

关键词： Induced pluripotent stem cells Reprogramming Cell-based therapy Stem cell banking Disease modelling

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Capsule enteroscopy is useful for the therapeutic management of Crohn's disease

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World Journal of Gastroenterology 2015年第44期21卷 12660-12666页

作者： joao Santos-Antunes Hélder Cardoso Susana lopes Margarida Marques Amadeu CR Nunes Guilherme Macedo Gastroenterology Department Faculty of Medicine Hospital de Sao Joao Department of Biochemistry (U38-FCT) Faculty of Medicine University of Porto

AIM: To analyze therapeutic changes in Crohn's disease(CD) patients following video capsule endoscopy(VCE) and to assess the usefulness of Lewis score and the Patency ***: Patency Capsule was performed in every patient that had indication for VCE, and those with negative patency did not undergo VCE. Patients with established CD that underwent VCE between January 2011 and February 2014 were selected for this study; those with suspected CD were excluded, independent of VCE results, since our purpose was to address differences in therapeutic regimen in CD patients before and after VCE. Patients with inconclusive VCE were also excluded. Patients had to be free of non-steroidal anti-inflammatories for at least 1 mo. Those patients who met these criteria were allocated into one of three groups: Staging group(asymptomatic CD patients that underwent VCE for staging of CD), Flare group(patients with active CD), or Post-op group(CD patients evaluated for post-operative recurrence). Lewis score was calculated for every VCE procedure. Statisticalanalysis was performed to address the impact of VCE findings on the therapeutic management of CD patients and to evaluate the utility of the Lewis ***: From a total of 542 VCEs, 135 were performed in patients with CD. Patency capsule excluded nearly 25% of the patients who were supposed to undergo VCE. No videocapsule retention during VCE was reported. From these 135 patients, 29 were excluded because CD diagnosis was not established at the time of VCE. Therefore, a total of 106 patients were included in the final analysis. From these, the majority were in the Staging group(n = 73, 69%), and the remaining were in the Flare(n = 23, 22%) or Post-op(n = 10, 9%) group. Median time between diagnosis and VCE was 5.5 years. Overall, VCE determined changes in the treatment of 40% of patients: only 21% remained free of immunosuppressors after VCE compared to 44% before VCE(P < 0.001). The differences in therapy before and a

关键词： Capsule enteroscopy Crohn's disease Treatment modification Patency capsule Lewis score

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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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Animal models of acute gastric mucosal injury: Macroscopic and microscopic evaluation

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Animal Models and Experimental Medicine 2019年第2期2卷 121-126页

作者： Sandra Simoes Rui lopes Maria Celeste Dias Campos Maria joao Marruz Maria Eugenia Meirinhos da Cruz Luisa Corvo Faculdade de Farmacia Instituto de Investigacao do Medicamento (iMed. ULisboa) Universidade de Lisboa Lisboa Portugal Servico de Anatomia Patologica Hospital Curry Cabral Lisboa Portugal ANATOMIK Avenida Campo Grande 168 1700‐094 Lisboa Portugal Hospital do Mar Bobadela Portugal

Acute gastric mucosal injury is a common disorder of the gastrointestinal tract and the search for new therapeutics is ongoing. The aim of this study is to update and expand the information related to the most widely used rat models of acute gastric ulcer, the ethanol‐induced ulcer and the indomethacin‐induced ulcer. These two models are compared in terms of macroscopic and microscopic features. Experimentally, ethanol was given orally in a single dose and indomethacin was subcutaneously injected into male Wistar rats. After ulcerative challenges, the stomachs were removed and visually inspected. Anti‐ulcerative drugs were used to validate the models. Histological analysis of the stomachs determined the microscopic score. The methodology used for model evaluation applied to macroscopic and microscopic gastric lesions. With these methods it was possible to induce lesions in the gastric mucosa. Microscopic evaluation permitted assessment of the inflammatory and apoptotic impact in the mucosa not observable by macroscopic evaluation. Groups of animals were treated with two standard drugs: sulcralfate suspension or lansoprazole solution. Both drugs reduced macroscopic and microscopic lesions, particularly the hemorrhagic ones. Both models induced acute gastric mucosal injury and no single evaluation method can address all the aspects of the pathology of gastric lesions. As a complement to macroscopic evaluation, microscopy appears to be a relevant tool to selectively identify specific aspects of the development of mucosal injury, quantify the extent of lesions, and contribute to an appropriate interpretation of results. The score systems established here offer a reliable method for testing antiulcer drugs.

关键词： animal models gastric ulcer histology pre-clinical assays

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Does intensity really matter regarding aerobic exercise reductions in wave reflection and central hemodynamics?Commentary on“The effect of acute aerobic exercise on central arterial stiffness,wave reflections,and hemodynamics in adults with diabetes:A randomized cross-over design”by Way et al.

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Journal of Sport and Health Science 2021年第4期10卷 507-509页

作者： Wendell Arthur lopes joao Carlos Locatelli Caroline Ferraz Simoes Rogerio Toshiro Passos Okawa Department of Physical Education Center of Health SciencesState University of MaringaMaringa 87020-900Brazil Postgraduate in Physical Education Program Center of Health SciencesState University of MaringaMaringa 87020-900Brazil Research Group on Systemic Arterial Hypertension Arterial Stiffness and Vascular Aging(GPHARV)Maringa 87020-900Brazil Department of Medicine Center of Health SciencesState University of MaringaMaringa 87020-900Brazil

We read with great interest the study by Way et al.1 published in this journal,which described and compared the acute changes in central arterial stiffness(AS),wave reflections,and central hemodynamics(CH)in response to a bout of high-intensity interval exercise(HIIE)and moderate-intensity continuous exercise(MICE)in adults with *** authors reported a significant reduction in augmentation index(AIx)corrected by a heart rate(HR)of 75 beats/min(AIx@75)and central systolic blood pressure after HIIE,without significant changes in the pulse wave velocity(PWV).In view of this important research topic and our recent contributions to it,we would like to raise some points of discussion that might help to better elucidate the findings observed in the current study,and also suggest pertinent directions to further studies.

关键词： stiffness intensity wave

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Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine

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Military Medical Research 2023年第5期10卷 699-725页

作者： Daniela lopes Joana lopes Miguel Pereira-Silva Diana Peixoto Navid Rabiee Francisco Veiga Omid Moradi Zhan-Hu Guo Xiang-Dong Wang joao Conde Pooyan Makvandi Ana Claudia Paiva-Santos Department of Pharmaceutical Technology Faculty of Pharmacy of the University of CoimbraUniversity of Coimbra3000-548 CoimbraPortugal REQUIMTE/LAQV Group of Pharmaceutical TechnologyFaculty of Pharmacy of the University of CoimbraUniversity of Coimbra3000-548 CoimbraPortugal School of Engineering Macquarie UniversitySydneyNsW 2109Australia Centre for Molecular Medicine and Innovative Therapeutics Murdoch UniversityPerthWA 6150Australia Department of Chemistry Shahr-e-Qods BranchIslamic Azad UniversityTehran 374-37515Iran lntegrated Composites Laboratory(iCL) Department of Mechanical and Construction EngineeringNorthumbria UniversityNewcastle Upon Tyne NE18STUK Department of Pulmonary and Critical Care Medicine Zhongshan HospitalFudan University Shanghai Medical CollegeShanghai 200032China Faculdade de Ciencias Medicas NOVA Medical SchoolUniversidade Nova de Lisboa1169-056 LisbonPortugal Centre for Toxicogenomics and Human Health GeneticsOncology and Human ToxicologyFaculdade de Ciencias MedicasNOVA Medical SchoolUniversidade Nova de Lisboa1169-056 LisbonPortugal school of Engineering Institute for Bioengineeringthe University of EdinburghEdinburgh EH93JLUK.

A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes,such as natural cell membranes or subcellular structure-derived *** strategy endows cloaked nanomaterials with improved interfacial properties,superior cell targeting,immune evasion potential,and prolonged duration of systemic ***,we summarize recent advances in the production and application of exosomal membrane-coated *** structure,properties,and manner in which exosomes communicate with cells are first *** is followed by a discussion of the types of exosomes and their fabrication *** then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering,regenerative medicine,imaging,and the treatment of neurodegenerative ***,we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.

关键词： Biomimetic Cell membrane coating Exosome Exosomal-membrane-coated nanoparticle Extracellular vesicle(EV)

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^(99m)Tc in the evaluation of microleakage of composite resin restorations with SonicFill^(TM).An in vitro experimental model

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Open Journal of Stomatology 2012年第4期2卷 340-347页

作者： Carrilho Eunice Abrantes Margarida casalta-lopes joao Botelho Filomena Paula Anabela Ambrósio Pedro Marto Carlos Miguel Rebelo Diana Marques Joana Polido Mário Ferreira Manuel Marques Faculty of Medicine University of CoimbraCoimbraPortugal

Introduction: The composite SonicFillTM (Kerr/Kavo) is indicated for posterior restorations, with a single increment up to 5 mm due to reduced polymerization shrinkage, thus reducing working time. Aim: Evaluation of marginal microleakage with SonicFillTM. Method and Materials: There were sectioned sixty noncarious human molars in the occluso-cervical direction. Class V cavities were prepared on each tooth with gingival margin walls in a standardized way. The specimens were divided into 4 groups: group 1—restored with SonicFillTM (Kerr/Kavo), group 2—restored with FiltekTM SupremeXTE (3M ESPE), group 3—the cavities were not restored;group 4—restored with SonicFillTM (Kerr/Kavo). In groups 1, 2 and 4 the enamel was conditioned with 37% orthophosphoric acid and applied the self-etch adhesive system Clear- fillTM SE BOND (Kuraray). The specimens were stored in distilled water at 37?C for 7 days. After, the specimens, were immersed in a solution of 99mTc-Pertechnetate and the radioactivity was assessed with a gamma camera. The nonparametric Kruskal-Wallis and Mann-Whitney test with Bonferroni correction at a significance level of 5% were used for the statistical analyses. Results: There are significant differences between the positive and negative control groups and between these and experimental groups (p TM and FiltekTM SupremeXTE. Conclusion: The new composite SonicFillTM and FiltekTM SupremeXTE showed no difference concerning dye penetration. The Sonic- FillTM restorative system showed no influence in concerning microleakage.

关键词： Posterior resin Composites Composite Restorations Polymerization Stress Polymerization Shrinkage Microleakage Thermocycling

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Smart Transformer/Large Flexible Transformer

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CES Transactions on Electrical Machines and Systems 2020年第4期4卷 264-274页

作者： Rongwu Zhu Markus Andresen Marius Langwasser Marco Liserre joao Pecas lopes Carlos Moreira Justino Rodrigues Mario Couto Chair of Power Electronics Kiel UniversityGermany

Solid-state transformer-based smart transformer(ST)can provide the dc connectivity and advanced services to improve the grid performance and to increase the penetration of the power electronics interfaced resources(e.g.,distributed generators and electric vehicle charging stations)in modern electricity distribution *** the ST is a new and effective paradigm of the electricity grid evolution to well understand the ST,this paper systematically presents the basic architecture and the typical control schemes of the ST and then the advanced services that ST can provide to improve the electricity grids performances in terms of the power flow control,power quality improvement,active damping and active contribution to improve distribution grid resilience by means of enabling autonomous microgrids operation as well as launching a restoration procedure following a general blackout.

关键词： Smart Transformer voltage control power quality active distribution grid black start

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