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Regulation mechanisms of endocrine disruptors on vasodilation andvasoconstriction: Insights from ex vivo models

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BIOCELL 2022年第6期46卷 1383-1389页

作者： MARGARIDA LORIGO ELISA CAIRRAO cics-ubi Health Sciences Research CentreUniversity of Beira InteriorCovilhã6200-506Portugal FCS-ubi Faculty of Health SciencesUniversity of Beira InteriorCovilhã6200-506Portugal

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. The knowledge andunderstanding of CVD are based on the study of vascular physiology and how the smooth muscle cells and tissuesperform their different functions. Exposure to endocrine disruptors (EDCs), such as phytoestrogens, polycyclicaromatic hydrocarbons, flame retardants, plasticizers, pesticides, and cosmetics, is an integral and fundamental part ofhuman exposure. Humans are exposed to EDCs by multiple pathways including air, food, water, and consumerproducts. However, this exposure can lead to several adverse effects on human health, including on the cardiovascular(CV) system. The negative impact that EDC toxicity has on human CV health is a serious problem that must not beoverlooked. In this point of view, we proposed the use of the human umbilical artery as a human model to study thedirect effects of EDCs on the vascular level. Several works where these cells were directly exposed to EDC’s werepresented to highlight this well-established model as a great strategy to be used. In the future, we emphasize the needto continue to carry out different investigations using HUA to unveil and understand the vascular toxicity of EDCsand improve human CV health.

关键词： Vascular tonus Human umbilical artery Human exposome

G protein-coupled estrogen receptor 1(GPER) activation triggers different signaling pathways on neurons and astrocytes

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Neural Regeneration Research 2019年第12期14卷 2069-2070页

作者： Claudio Roque Graca Baltazar cics-ubi - Health Sciences Research Centre University of Beira Interior Covilh. Portugal Faculty of Health Sciences University of Beira Interior Covilh. Portugal

Estradiol (E2) is the most potent and prevalent form of estrogen, a well-known hormone that regulates multiple tissues and functions in humans. In the brain, E2 regulates processes as diverse as learning, memory, cognition, mood, as well as neurodevelopment and neurodegeneration. The actions of E2 are mediated by classical estrogen receptors (ERs;α and β), and by the G protein-coupled estrogen receptor 1 (GPER or GPR30)(Prossnitz and Arterburn, 2015). Classical ER are predominantly present in the nucleus and cytoplasm, with less than 2% present on the plasma membrane, and mediate genomic cellular effects that occur in the time frame of hours to days (Prossnitz and Arterburn, 2015).

关键词： multiple tissues functions astrocytes

Functionalization of AuMSS nanorods towards more effective cancer therapies

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Nano Research 2019年第4期12卷 719-732页

作者： Carolina F. Rodrigues Telma A. Jacinto Andre F. Moreira Elisabete C. Costa Sonia P. Miguel Ilidio J. Correia cics-ubi -Centro de Investigagao em Ciencias da Saude Universidade da Beira Interior Covilhd 6200-506 Portugal CIEPQF - Departamento de Engenharia Quimica Universidade de Coimbra Rua 13 Silvio Lima Coimbra 3030-790 Portugal

The applicatio n of nano particles as selective drug delivery platforms arises as one the most promising therapeutic strategies in the biomedical field. Such systems can encapsulate drugs, prevent its premature degradation, transport and promote the drugs specific delivery to the target site. Among the different nanostructures, gold-core mesoporous silica shell (AuMSS) nanorods have been one of the most explored due to their unique physical and chemical properties. The mesoporous silica biocompatibility, high surface area that can be easily functionalized, tubular pores that can store the drugs, conjugated with the intrinsic capacity of gold nanorod to absorb near-infrared radiation, allows the combination of hyperthermia (i.e., photothermal effect) with drug delivery, making them a nanoplatforms with a huge potential for cancer therapy. Nevertheless, the successful applicati on of AuMSS nanoparticles as an effective can cer nano medicine is hindered by the uncon trolled release of the therapeutic payloads, limited blood circulation time and unfavorable pharmacokinetics. In this review, an overview of the modificati ons performed to improve the AuMSS nano rods applicati on in nanom edicine is provided, highlighting the practical approaches that enhaneed the AuMSS nanorods targeting, responsiveness to different stimuli, and blood circulation time. Further, the basics of AuMSS nano rods syn thesis procedures, gen eral properties, and its applicati on in can cer therapy are also described.

关键词： gold nano rods silica surface modifications targeting cancer

Contribution of glial cells to the neuroprotective effects triggered by repetitive magnetic stimulation:a systematic review

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Neural Regeneration Research 2024年第1期19卷 116-123页

作者： Susana A.Ferreira Nuno Pinto Inês Serrenho Maria Vaz Pato Graça Baltazar Centro de Investigação em Ciências da Saúde(cics-ubi) Universidade da Beira InteriorCovilhãPortugal Faculdade de Ciências da Saúde Universidade da Beira InteriorCovilhãPortugal GRubi-Systematic Reviews Group University of Beira InteriorCovilhãPortugal

Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly *** systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online *** of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were *** protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte *** trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst *** papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete *** what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of *** is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magneti

关键词： astrocyte glia high-frequency repetitive magnetic stimulation inflammation low-frequency repetitive magnetic stimulation microglia neurologic disorders oligodendrocyte repetitive magnetic stimulation theta-burst stimulation

Liquid chromatographic methods for determination of the new antiepileptic drugs stiripentol, retigabine, rufinamide and perampanel: A comprehensive and critical review

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Journal of Pharmaceutical Analysis 2021年第4期11卷 405-421页

作者： Sara Meirinho Marcio Rodrigues Ana Fortuna Amílcar Falcao Gilberto Alves Faculty of Health Sciences Health Sciences Research CenterUniversity of Beira Interior(CICS UBI)6200-506CovilhaPortugal Research Unit for Inland Development Polytechnic Institute of Guarda(UDI-IPG)6300-654GuardaPortugal Coimbra Institute for Biomedical Imaging and Translational Research(CIBIT) University of Coimbra3000-548CoimbraPortugal Laboratory of Pharmacology Faculty of PharmacyUniversity of Coimbra3000-548CoimbraPortugal

The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy *** them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be ***,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system *** different liquid chromatographic(LC)methods coupled with ultraviolet,fluorescence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet ***,this review summarizes the main analytical aspects regarding the liquid chromatographic methods developed for the analysis of perampanel,retigabine(and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage ***,the physicochemical and stability properties of the target compounds will also be ***,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new(bio)analytical techniques are aimed to be implemented for these drugs.

关键词： Bioanalysis Liquid chromatography Perampanel Retigabine Rufinamide Stiripentol

Anti-obesity drugs currently used and new compounds in clinical development

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World Journal of Meta-Analysis 2014年第4期2卷 135-153页

作者： Armindo Martins Sandra Morgado Manuel Morgado cics-ubi-Health Sciences Research Center University of Beira Interior6201-001 CovilhaPortugal Hospital Centre of Cova da Beira 6200-251 CovilhaPortugal

Obesity is a chronic disease which requires treatment. As lifestyle interventions alone hardly ever result in long-term weight loss, pharmacotherapy is an impor-tant adjunct to lifestyle measures to improve the induc-tion and maintenance of weight loss. Owing to the lim-ited options currently available for the pharmacological treatment of obesity, it is imperative to develop new safe compounds. This study aims to review the current medications approved by European Medicines Agency and United States Food and Drug Administration （FDA） for the treatment of obesity, focusing essentially on their benefits and risks, as well as on the new drugs which are presently under clinical trials. Moreover, it lists the anti-obesity agents that have been recently withdrawn from the market. A revision of the scientifc literature was carried out, through a search on Pubmedfor papers published from January 2010 to January2013. Orlistat （Xenical？） is currently the only long-termpharmacotherapy for obesity available in the Europeanmarket, as rimonabant and sibutramine were with-drawn in 2008 and 2010, respectively, due to serious psychiatric and cardiovascular adverse effects. Lorca-serin （Belviq？） and the association of phentermine and topiramate （QsymiaTM） were recently approved by FDA. Orlistat suppresses appetite inhibiting gastrointestinal lipase, being its adverse effects mostly gastrointestinal. Lorcaserin activates 5-HT2C receptors, phentermine is a norepinephrine releasing drug, and topiramate is an anticonvulsivant drug with weight loss properties.

关键词： Obesity Weight loss Pharmacological treatment European Medicines Agency Food and Drug Administration Clinical trials

Novel synthetic opioids-toxicological aspects and analysis

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Forensic Sciences Research 2019年第2期4卷 111-140页

作者： Inês Tabarra Sofia Soares Tiago Rosado Joana Gonçalves Àngelo Luís Sara Malaca Mário Barroso Thomas Keller José Restolho Eugenia Gallardo Centro de Investigação em Ciências da Saude(cics-ubi) Universidade da Beira InteriorCovilhãPortugal Laboratorio de Fármaco-Toxicologia-ubiMedical Universidade da Beira InteriorCovilhãPortugal Serviço de Química e Toxicologia Forenses Instituto Nacional de Medicina Legal e Ciências ForensesDelegac¸ão do SulLisboaPortugal Departament of Toxicology Institute of Forensic MedicineSalzburgAustria nal von minden GmbH RegensburgGermany

Over the past few years,there has been an emerging number of new psychoactive *** drugs are frequently mentioned as“legal highs”,“herbal highs”,“bath salts”and“research chemicals”.They are mostly sold and advertised on online forums and on the dark *** emerging new psychoactive substances are designed to mimic the effects of psychoactive groups,which are often abused *** synthetic opioids are a new trend in this context and represent an alarming threat to public *** the wide number of fatalities related to these compounds reported within the last few years,it is an important task to accurately identify these compounds in biologic matrices in order to administer an effective treatment and reverse the respiratory depression caused by opioid related *** dealing with fentanyl intoxication cases should consider that it could,in fact,be a fentanyl *** this reason,it is a helpful recommendation to include synthetic opioids in the routine toxicological screening procedures,including analysis in alternative matrices,if available,to investigate poly-drug use and possible tolerance to *** address this public health problem,better international collaboration,effective legislation,effective investigation,control of suspicious“research chemicals”online forums and continuous community alertness are *** article aims to review diverse reported fatalities associated with new synthetic opioids describing them in terms of pharmacology,metabolism,posology,available forms,as well as their toxic effects,highlighting the sample procedures and analytical techniques available for their detection and quantification in biological matrices.

关键词： Forensic sciences forensic toxicology new synthetic opioids biological specimens toxicity analysis

Genetic testing vs microforceps biopsy in pancreatic cysts:Systematic review and meta-analysis

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World Journal of Gastroenterology 2019年第26期25卷 3450-3467页

作者： Sandra Faias Luisa Pereira Angelo Luis Paula Chaves Marilia Cravo Department of Gastroenterology Instituto Portugues de Oncologia de Lisboa de Francisco GentilEPELisboa 1099-023Portugal Faculdade de Ciencias da Seude Universidade da Beira InteriorCovilha 200-506Portugal GRubi-Grupo de Revisoes Sistematicas Universidade da Beira InteriorCovilha 6200-506Portugal Centro de Matemática e Aplicacoes(CMA-ubi) Universidade da Beira InteriorCovilha 6200-506Portugal Centro de Investigacao em Ciencias da Saude(cics-ubi) Universidade da Beira InteriorCovilha 6200-506Portugal Department of Pathology Instituto Portugues de Oncologia de Lisboa de Francisco GentilEPELisboa 1099-023Portugal Department of Gastroenterology Hospital Beatriz AngeloLoures 2674-514Portugal Faculdade de Medicina Universidade de LisboaLisboa 1099-023Portugal

BACKGROUND Carcinoembryonic antigen(CEA)and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic *** testing and microforceps biopsy are promising tools for pre-operative diagnostic improvement but comparative performance of both methods is *** To compare the accuracy of genetic testing and microforceps biopsy in pancreatic cysts referred for *** We performed a literature search in Medline,Scopus,and Web of Science for studies evaluating genetic testing of cystic fluid and microforceps biopsy of pancreatic cysts,with endoscopic ultrasound with fine-needle aspiration(EUSFNA)prior to surgery and surgical pathology as reference standard for *** evaluated the diagnostic accuracy for:1-benign cysts;2-mucinous low-risk cysts;3-high-risk cysts,and the diagnostic yield and rate of correctly identified cysts with microforceps biopsy and molecular *** also assessed publication bias,heterogeneity,and study *** Eight studies,including 1206 patients,of which 203(17%)referred for surgery who met the inclusion criteria were analyzed in the systematic review,and seven studies were included in the *** testing and microforceps biopsies were identical for diagnosis of benign *** analysis was superior for diagnosis of both low and high-risk mucinous cysts,with sensitivities of 0.89(95%CI:0.79-0.95)and 0.57(95%CI:0.42-0.71),specificities of 0.88(95%CI:0.75-0.95)and 0.88(95%CI:0.80-0.93)and AUC of 0.9555 and 0.92,*** diagnostic yield was higher in microforceps biopsies than in genetic analysis(0.73 vs 0.54,respectively)but the rates of correctly identified cysts were identical(0.73 with 95%CI:0.62-0.82 vs 0.71 with 95%CI:0.49-0.86,respectively).CONCLUSION Genetic testing and microforceps biopsies are useful second tests,with identical results in benign pancreatic *** analysis performs better for low-and high-risk cysts but has lower diagnos

关键词： Pancreatic cysts Endoscopic ultrasound Endoscopic ultrasound with fineneedle aspiration Genetic testing Microforceps biopsy Molecular analysis KRAS Carcinoembryonic antigen Cytology

A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers

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Translational Neurodegeneration 2020年第2期9卷 118-131页

作者： Sandra I.Anjo Patrícia Valério dos Santos Luiza Rosado Graça Baltazar Inês Baldeiras Diana Pires Andreia Gomes Cristina Januário Miguel Castelo-Branco Mário Grãos Bruno Manadas CNC-Center for Neuroscience and Cell Biology University of CoimbraCoimbraPortugal Faculty of Medicine University of CoimbraCoimbraPortugal Centro de Investigação em Ciências da Saúde(cics-ubi) Universidade da Beira InteriorCovilhãPortugal Centro Hospitalar Cova da Beira E.P.ECovilhãPortugal Neurology Department Centro Hospitalar e Universitário de CoimbraCoimbraPortugal Coimbra Institute for Biomedical Imaging and Translational Research(CIBIT) CoimbraPortugal Biocant Biotechnology Transfer AssociationCantanhedePortugal Institute for Interdisciplinary Research University of Coimbra(IIIUC)CoimbraPortugal

Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease(PD)has failed several times in the ***,in this pilot study,a translational approach was conducted,allowing the evaluation of the plasma levels of two mitochondrial-related proteins,whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched *** The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions,followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two *** pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD *** From the secretome analysis,several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two ***,two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched ***,a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two *** proteins are associated with apoptotic mitochondrial changes,which may correspond to potential indicators of cell ***,one of these proteins,the VPS35 protein,was reported in plasma for the first time,and its quantification was only possible due to its previous identification in the secretome *** In this work,an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases,in the present case Parkinson’s *** novelty and success of this pilot study may arise from the combination of:i)a translational research pipeline,where plasma samples are interrogated using knowledge previously ob

关键词： Mitochondrial-related proteins SWATH-MS Parkinson's disease Biomarker discovery Blood-biomarker Secretomes Oxidative stress