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Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

World Journal of Diabetes 2015年第6期6卷 807-827页

作者： Emanuel Monteiro Candeias Inês Carolina Sebastio susana maria cardoso Sónia Catarina Correia Cristina Isabel Carvalho Ana Isabel Plácido maria Sancha Santos Catarina Resende Oliveira Paula Isabel Moreira Ana Isabel Duarte CNC-Center for Neuroscience and Cell Biology Rua Larga Faculty of Medicine (1st Floor) University of Coimbra Institute for Interdisciplinary Research (IIIUC) University of Coimbra Casa Costa Alem?o-Pólo II Rua D Francisco de Lemos 3030-789 Coimbra Portugal Faculty of Medicine University of Coimbra Life Sciences Department University of Coimbra Largo Marquês de Pombal 3004-517 Coimbra Portugal Institute of Biochemistry Faculty of Medicine University of Coimbra Institute of Physiology Faculty of Medicine University of Coimbra

Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia in

关键词： Type 2 diabetes Glucagon-like peptide-1 Gut Brain Insulin Liraglutide Alzheimer disease Neuroprotection

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A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions

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Microsystems & Nanoengineering 2023年第5期9卷 203-217页

作者： Catarina Gonçalves Fonseca Vânia Silvério David Barata Wolfgang Giese Holger Gerhardt susana cardoso Claudio Areias Franco Instituto de Medicina Molecular João Lobo Antunes Faculdade de MedicinaUniversidade de LisboaLisboaPortugal INESC Microsistemas and Nanotecnologias INESC-MNLisboaPortugal Department of Physics Instituto Superior TécnicoUniversidade de LisboaLisboaPortugal Max Delbrück Center for Molecular Medicine BerlinGermany DZHK(German Centre for Cardiovascular Research) Partner Site BerlinBerlinGermany Charité–Universitätsmedizin Berlin BerlinGermany Universidade Católica Portuguesa Católica Medical SchoolCatólica Biomedical Research CentreLisbonPortugal

The ability of endothelial cells to respond to blood flow is fundamental for the correct formation and maintenance of a functional and hierarchically organized vascular *** flow responses,in particular related to high flow conditions,have been associated with atherosclerosis,stroke,arteriovenous malformations,and neurodegenerative ***,the molecular mechanisms involved in high flow response are still poorly ***,we described the development and validation of a 96-wells fluidic system,with interchangeable cell culture and fluidics,to perform high-throughput screenings under laminar high-flow *** demonstrated that endothelial cells in our newly developed 96-wells fluidic system respond to fluid flow-induced shear stress by aligning along the flow direction and increasing the levels of KLF2 and *** further demonstrate that our 96-wells fluidic system allows for efficient gene knock-down compatible with automated liquid handling for high-throughput screening ***,we propose that this modular 96-well fluidic system is an excellent platform to perform genome-wide and/or drug screenings to identify the molecular mechanisms involved in the responses of endothelial cells to high wall shear stress.

关键词： system laminar fluid

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Effectiveness of Acupuncture on Pain, Physical Function and Health-Related Quality of Life in Patients with Rheumatoid Arthritis: A Systematic Review of Quantitative Evidence

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Chinese Journal of Integrative Medicine 2019年第9期25卷 704-709页

作者： susana Seca Diana Miranda Daniela cardoso Bernice Nogueira Henry J.Greten Antonio Cabrita Manuel Alves Rodrigues Faculty of Medicine University of CoimbraInstitute of Science Biomedicine Abel Salazar University of Porto Porto PortugalHeidelberg School of Chinese Medicine Heidelberg Germany Institute of Science Biomedicine Abel Salazar University of Porto Porto Portugal Health Sciences Research Unit:Nursing (UICISA: E) Nursing School of Coimbra (ESEnfC) Portugal Centre for Evidenee Based Practice: A Joanna Briggs Institute Centre of Excellence Coimbra Portugal School of Health Sciences Macao Polytechnic Institute Macao SAR China Institute of Science Biomedicine Abel Salazar University of PortoHeidelberg School of Chinese Medicine Heidelberg Germany Faculty of Medicine University of Coimbra Portugal Health Sciences Research Unit: Nursing (UICISA:E) Nursing School of Coimbra (ESEnfC)Portugal Centre for Evidence Based Practice: A Joanna Briggs Institute Centre of Excellence Portugal

Objective: To identify and synthesize the most recent available evidence of effectiveness of acupuncture on pain, physical function and health-related quality of life(HRQoL) in patients with rheumatoid arthritis(RA). Methods: A comprehensive search of 12 Western and Chinese databases was undertaken from their inception up to end of 2016. Randomized controlled trials(RCTs), concerning patients with RA treated with needle acupuncture, written in English, Portuguese, German or Chinese were included. Primary outcomes included pain, physical function and HRQoL. Secondary outcomes included morning stiffness, functional impairment, number of tender and swollen joints and serum concentrations of inflamatory markers. Methodological quality was assessed by three independent reviewers using the standardized critical appraisal instrument from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. Results: Twenty-two studies met the inclusion criteria. Of those, 9 studies were excluded after assessment of their methodological quality. The remaining 13 original RCTs included 974 patients. Ten of these studies published in China, showed favorable statistical significant effects of acupuncture in relieving symptoms of RA compared with controls. Conclusions: Evidence suggests that acupuncture interventions may have a positive effect in pain relief, physical function and HRQo L in RA patients. However, due to the heterogeneity and methodologic limitations of the studies included in this systematic review, evidence is not strong enough to produce a best practice guideline.

关键词： acupuncture rheumatoid arthritis quality of life pain physical function randomized clinical trial

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Sol-Gel Relative Humidity Sensors: Impact of Electrode Geometry on Performance in Soil Suction Measurements

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Journal of Sensor Technology 2017年第1期7卷 1-23页

作者： Rafaela cardoso Gabriele Sarapajevaite Oleksandr Korsun susana cardoso Laura Ilharco Instituto Superior Técnico (IST) Universidade de Lisboa Lisbon Portugal Civil Engineering Research Innovation and Sustainability (CERIS) Institute of Construction Structures and Territory of IST (ICIST) Lisbon Portugal INESC-MN Microsystems and Nanotechnologies Lisbon Portugal CQFM Centro de Química-Física Molecular Instituto Superior Técnico (IST) Lisbon Portugal

This paper describes the experimental procedure followed to fabricate and validate sol-gel based RH sensors which will be incorporated in soil specimens for standard laboratorial tests. It is the first time such sensors were used for soil suction measurement. They are microfabricated relative humidity sensors (footprint area 11,000 μm × 22,000 μm) operating based on changes in electrical resistivity detected by a cerium doped silica titania film deposited using a sol-gel technique. Their design required gathering experts in several engineering specialties. The working principle of the sensors is based on water vapour equilibrium between the air in the soil and in the sol-gel pores, due to the contact between the two porous materials. The spacing between interdigitated aluminium electrodes was optimized to improve the sensing properties of the sol-gel. The calibration of the different prototypes was done against compacted clay, varying the spacing between 100 and 700 μm. The sensors were also incorporated in soil samples for suction measurement during wetting and drying paths. They were validated by comparing the readings with those from a water dew point potentiometer. From this study it was possible to determine the optimum electrodes spacing of 200 μm. Error was explained by sol-gel heterogeneity effect and by the resolution of the sensing area provided by the electrodes spacing. When comparing with other sensors operating inside soil specimens in standard laboratorial tests, these sol-gel sensors extend the operation range available with the alternative technologies: while conventional tensiometers measure suction ranges from 0 to 1.8 MPa, our sensors demonstrate good results between 1 to 10 MPa (and higher).

关键词： Microfabricated Interdigitated Electrodes Humidity Sensors Suction Unsaturated Soils

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Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy:A single center report of 8 cases

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World Journal of Gastroenterology 2015年第24期21卷 7584-7588页

作者： susana Rodrigues susana Lopes Fernando Magro Hélder cardoso Ana maria Horta e Vale Margarida Marques Eva Mariz Miguel Bernardes Joanne Lopes Fátima Carneiro Guilherme Macedo Department of Gastroenterology Centro Hospitalar de Sao Joao Department of Rheumatology Centro Hospitalar de Sao Joao Department of Pathology Centro Hospitalar de Sao Joao Institute of Molecular Pathology and Immunology at the University of Porto

This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis(AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

关键词： Anti-tumor necrosis factor antagonist Autoimmune hepatitis Adalimumab Drug-induced liverinjury Inflammatory bowel disease Infliximab

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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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