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Biosystems in Toxicology and Pharmacology – Current challenges
8–9 Sep 2022
Biomolecular Systems, Alternative Methods, Biodevices, Biological Response, Metallodrugs, Biological Barriers, Biomaterials, Biological Drugs, Biodetection
- Go to the Sessions
- Event Details
Welcome from the Chairs
Abstract and Manuscript submissions after the indicated deadlines are acceptable and will be considered case-by-case according to the program of the Meeting
Biological systems and models provide essential platforms for the evaluation of drugs and toxicants. From biomolecular systems comprising enzymes or antibodies to a panoply of existing cell culture models, different bio-based systems became important tools to study toxicological and pharmacological responses. The great progresses in health care, drug development, food and environmental safety did not left behind the in vitro approaches. By the contrary, keeping pace with biological knowledge and biofabrication technologies, the expectations are high in the development of novel, multifunctional, integrated, accessible, increasingly bio-informative solutions.
This Meeting aims to stimulate the research on the development and applications of biomolecular systems. Some topics in the crossroads of Toxicology and Pharmacology are initially set to promote the exchange of ideas, and the program is open to other, innovative, concepts and practical approaches addressing issues in those fields and Molecular Biosciences in general.
Topics of interest include, but are not limited to:
- Cell culture systems replicating in vivo conditions
- Biodevices and functional tissues for disease modelling
- Target identification and network pharmaco/toxicology
- Non-animal and human-relevant approaches
- Barrier mimicking and drug delivery systems
- Bioactive compounds and materials
- Responses to mixtures, emergent pollutants, food ingredients and impurities in pharmaceuticals
- Biosensors for diagnostic, environmental and industrial applications
- Development of vaccines and cell therapies
- Integration with modelling and computational methods.
We invite all the interested in the development of new bioanalytical and research methods to share their experience and participate in this forum.
Event Chairs
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Scientific Committee
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Félix Carvalho, PharmD, PhD, ERT, is Full Professor of Toxicology at the Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto (FFUP). Félix Carvalho is currently: - President of EUROTOX (Association of European Toxicologists and European Societies of Toxicology); - President of the North Regional Section of the Portuguese Order of Pharmacists; - President of the Scientific Council of FFUP; - Vice-Director of the Research Unit on Applied Molecular Biosciences (UCIBIO), Portugal; - Member of the Member of the Medicines Evaluation Committee of INFARMED. The Portuguese Authority of Medicines and Health Products. - Associate member/member of the Editorial Board of several Scientific Journals in the areas of Toxicology, Pharmacology and Pharmaceutical Sciences. During the past 30 years, Félix Carvalho has published over 450 scientific articles / book chapters, and is co-editor of the books “Toxicologia Forense“ and "Toxicologia Fundamental”. ORCID profile: https://orcid.org/0000-0003-3858-3494
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Mário S. Diniz has a MSc and a PhD in environmental sciences and is Assistant Professor at the Chemistry Department of the NOVA SCHOOL OF SCIENCE AND TECHNOLOGY (FCT-NOVA). He is an integrated member of the “Research Unit on Applied Molecular Biosciences (UCIBIO) and is the head of the research lab “Biotox Lab”, focused on Environmental Health, Safety and Toxicology. He is author or co-author of more than 145 articles in SCI journals, 10 book chapters, 3 articles in national peer review Journals, about 43 articles in conference proceedings (peer-reviewed) and more than 95 oral communications in scientific meetings or conferences. ORCID profile: https://orcid.org/0000-0003-1571-0366
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Victor Diculescu, PhD, Senior Researcher at the National Institute of Materials Physics, Bucharest, Romania, graduated the Faculty of Physics at University of Bucharest in 1998, has a MSc degree in Biophysics at the same faculty and received the PhD in Biochemistry-Biochemical Technology in 2005 at University of Coimbra, Portugal. The main activities involve the development and surface characterization of electrodes for (bio)sensing DNA, proteins and other relevant biomarkers. ORCID profile: https://orcid.org/0000-0003-0719-8016
Invited Speakers
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University of Florence (Italy),
Title: Emerging Biosensors for detecting food contaminants
Emerging Biosensors for detecting food contaminants
Giovanna Marrazza broad expertise includes preparation and evaluation of biosensors based on the coupling of electrochemical, optical and piezoelectric sensors with enzymes, antibodies, bacteria, Molecular Imprinted Polymers and aptamers. She also is an expert in analytical procedures suitable for use with biosensor devices, i.e. flow injection analysis, microflow systems, thick-film technology; nanodispensing technologies and Immobilization procedure of biomolecules on several supports. Techniques in molecular diagnostics (DNA extraction, polymerase chain reaction, DNA purification, protein–DNA complexes); Nanomaterials: carbon nanotubes, nanobeads, nanostructured and nanocomposite polymers. Profile: https://www.unifi.it/p-doc2-0-0-A-3f2a3d2c322e2f.html
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University of Extremadura (Spain),
Title: High-affinity molecular targets of amyloid β (1-42) peptide oligomers in neurons
High-affinity molecular targets of amyloid β (1-42) peptide oligomers in neurons
Professor of Biochemistry and Molecular Biology of the University of Extremadura. Author of more than 170 scientific publications, largely published in JCR-indexed journals. Over 40 invited oral communications in international and national meetings of Biochemistry and Molecular Biology, and Biophysics. Present research interests: molecular mechanisms of neurodegeneration induced by amyloid-β peptides and neurotoxins, and neuroprotection agents. Profile: https://orcid.org/0000-0003-3673-7007
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University of Porto (Portugal),
Tentative Title: Toxicology of the XXI century
Tentative Title: Toxicology of the XXI century
Félix Carvalho, PharmD, PhD, ERT, is Full Professor of Toxicology at the Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto (FFUP). Félix Carvalho is currently: - President of EUROTOX (Association of European Toxicologists and European Societies of Toxicology); - President of the North Regional Section of the Portuguese Order of Pharmacists; - President of the Scientific Council of FFUP; - Vice-Director of the Research Unit on Applied Molecular Biosciences (UCIBIO), Portugal; - Member of the Member of the Medicines Evaluation Committee of INFARMED. The Portuguese Authority of Medicines and Health Products. - Associate member/member of the Editorial Board of several Scientific Journals in the areas of Toxicology, Pharmacology and Pharmaceutical Sciences. During the past 30 years, Félix Carvalho has published over 450 scientific articles / book chapters, and is co-editor of the books “Toxicologia Forense“ and "Toxicologia Fundamental”. Profile: https://orcid.org/0000-0003-3858-3494
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Colorado State University (USA),
Title: Potential applications of vanadium-based anticancer drugs for intratumoral injections
Potential applications of vanadium-based anticancer drugs for intratumoral injections
My interest is the fundamental chemistry and biochemistry of drugs with particular interest in vanadium and other transition metal ions as metals in medicine and their mechanisms of toxicity. My group and I have synthesized new compounds and characterized them and tested their biological properties. We have been studying the fundamental coordination chemistry of vanadium and other transition metal compounds in aqueous solution and model systems for what might occur in the varied environments of biological systems. Studies of lipid systems and micro-emulsion environments help us understand how drugs and metabolites interact and penetrate lipid interfaces. Profile: https://cranslab.colostate.edu/crans-brief-resume/
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Center for Physical Sciences and Technology, Lithuania,
Title: Abilities of Graphene to Monitor Human Health
Title: Abilities of Graphene to Monitor Human Health
The research group performs investigations in: Development of new composites of functional nanomaterials and their electrochemical investigation; Development of conducting polymers from natural monomers and their investigation; Development of electrochemical sensors for medical, food analysis, and other applications employing natural polymers and graphene; Electrochemical investigations of cell metabolites. Profile: https://www.ftmc.lt/functional-nanomaterials-laboratory
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University of Coimbra, Portugal,
Title: Models and formulations to overcome the blood-brain barrier
Title: Models and formulations to overcome the blood-brain barrier
Lino Silva Ferreira holds a Ph.D. in Biotechnology from the University of Coimbra (Portugal). He did postdoctoral work at INEB (Portugal) and MIT (USA) in the group of Robert Langer in the areas of stem cells and nanotechnologies. He established his research group in 2008 at the University of Coimbra. Since then is the director of the Biomaterials and Stem Cell-Based Therapeutics research group, CNC coordinator of the MIT-Portugal Program and the founder of the biotech company Matera. He is also the associate editor of Biomaterials Science Journal (RSC). In 2012, he was awarded with a prestigious European Research Council starting grant and in 2016 a prestigious ERA Chair position at the University of Coimbra. His group has interest in the development of advanced therapies for ischemic diseases. Profile: http://erachair.uc-biotech.pt
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Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina,
Title: Finding new molecular targets of Copper(II) complexes on triple negative breast cancer cells using mass spectrometry-based quantitative proteomics
Finding new molecular targets of Copper(II) complexes on triple negative breast cancer cells using mass spectrometry-based quantitative proteomics
Ignacio León is a Associate Researcher in Centro de Química Inorgánica, a research institute from CONICET and National University of La Plata. He was born in Viedma in 1986, graduated in 2010 in Biotechnology, and completed his doctoral studies (Ph.D. in Biological Sciences) in 2015 in the National University of La Plata. From 2015 to 2016 he did a postdoctoral position in Salamanca University, Spain. In the middle of 2016 he joined Centro de Química Inorgánica as an Assistant Researcher and in 2019 he received an Associate Researcher position to work at the same institute. His research interests are mainly in the field of medicinal chemistry, especially in bioinorganic chemistry focused in the design, synthesis and biological studies of metal-based drugs as antitumor agents. He co-authored more than 55 publications and more than 75 conference presentations. Profile: https://www.conicet.gov.ar/new_scp/detalle.php?id=43308&datos_academicos=yes
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RWTH Aachen University, Germany,
Title: Metal-based cancer (nano)medicine
Metal-based cancer (nano)medicine
Quim Peña obtained his PhD degree in Chemistry from the Universitat Autònoma de Barcelona (Spain) and the Aix-Marseille Université (France) in 2019, focused on metal-based compounds as potential chemotherapeutics. He joined the Institute for Experimental Molecular Imaging at RWTH Aachen University in 2020 as a postdoctoral researcher. His current research deals with the use of nanomedicine for improved delivery of several organic- and metal-based (pro)drugs, in order to enhance their therapeutic efficiency and minimize the associated side-effects in cancer therapies. He is also involved in the synthesis of prodrugs and drug-loaded polymeric micelles projects. Profile: https://orcid.org/0000-0001-6477-8127
Detailed Program
*Attention: Times indicated are in Central European Summer Time (CEST)
Thursday 8 September 2022 |
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10:00 – 10:10 |
Welcome from the Chairs & Introduction |
Biosensors and BiodevicesChair: Victor C. Diculescu |
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10:10-10:40 |
Giovanna Marrazza - Emerging biosensors for detecting food contaminants |
10:40-11:10 |
Madalina Barsan - Proteasome biosensors and immunosensors for new diagnostic strategies and drug therapies in various diseases Ricardo Leote - Bienzymatic Biosensor for Pyruvate Kinase Inhibitors Screening for Cancer Treatment |
11:10-11:40 |
Rasa Pauliukaite - Abilities of Graphene to Monitor Human Health |
11:40-11:50 |
Coffee Break |
Biomimicking and BiobarriersChair: Maria João Moreno |
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11:50-12:45 |
Vanessa Domingues - Structure and stability of alpha-gliadin under INFOGEST-standard conditions Alejandro Samhan Arias - Structural characterization of caveolin-2 for generation of membrane nanodomains Dorinda Marques da Silva - Synthetic membranes as an alternative model to animal skin to investigate dermal permeation of chlorpyrifos Cristiana Pires - Bioavailability and biotransformation of paralytic shellfish toxins assessed by permeability assays using Caco‐2 monolayers |
12:45-13:15 |
Lino Ferreira - Models and formulations to overcome the blood-brain barrier |
13:15-14:15 |
Lunch |
ImmunomodulationChair: Paula Videira |
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14:15-14:50 |
Emma Browne - The cytotoxicity of phorbol 12- myristate 13-acetate and lipopolysaccharide on THP-1 cells and optimized differentiation protocol Mariana Barbosa - Targeting immune-mediated responses to tackle GNE myopathy |
Materials and Drug DeliveryChair: Mário Diniz |
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14:50-15:20 |
Quim Peña - Metal-based cancer (nano)medicine |
15:20-15:30 |
Coffee Break |
15:30-16:20 |
Carlos Coelho - BSA‐PEG hydrogel: A novel protein‐ligand binding 3D matrix Anca Aldea - Flexible sensors based on metallized electrospun polymeric fibers for sweat analysis Alexandra Pusta - Magnetic nano-carriers for the targeted delivery of antitumor drug sorafenib Cristiana Violante - Promotion of dermal permeation of bioactive compounds using a microneedle device |
16:20-16:50 |
Victor C. Diculescu - Electrospining for electrochemical applications |
16:50-17:00 |
Closing Remarks |
Friday 9 September 2022 |
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Targets and Advances in PharmacologyChair: Ricardo Lagoa |
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10:00-10:30 |
Carlos Gutiérrez Merino - High-affinity molecular targets of amyloid β (1-42) peptide oligomers in neurons |
10:30-11:15 |
Arnab Banerjee - Small extracellular vesicles (sEVs) imaging for clinical applications Sofia Viana - A voluntary, metabolic inert and animal welfare friendly tool for oral drug dosing – pill tech Akhileshwar Srivastava - In silico screening of the therapeutic paradigm of curcuminoids relative to conventional drugs for inactivation of SARS-CoV2 receptors |
11:15-11:25 |
Coffee Break |
11:25-12:00 |
Poster Sessions - 2 Parallel sessions for Flash PresentationsChairs: Dorinda Silva and Joaquim Rui Rodrigues Session I (room 1): Andreia Vilaça - Proteomic profiling of extracellular vesicles identifies source-specific molecular signature Caroline Sanz - Electrochemical characterization of shikonin and in-situ evaluation of interaction with DNA Daniela Oprea - Polymer nanofibers support for biosensing application in cell cultures Inês Ferreira - Deep eutectic systems: What methodology should we use to assess toxicity? Iris Correia - An insight into the nutritional profile and antioxidant activity of the sea fennel halophyte plant (Crithmum maritimum) Session II (room 2): Daciana Botta - Electrochemical Devices with Metallized Electrospun Fiber Meshes Electrodes Mihaela-Cristina Bunea - Degradation of azathioprine and its effects on DNA Magdolna Casian - Selection, characterization and use of Protein Golgi 73 specific aptamer as a tool for early-stage diagnosis of hepatocellular cancer Gil Fraqueza - Pharmacological, Antimicrobial and Toxicological Actions of Vanadium Compounds Magda Rodrigues - Freeze-dried small extracellular vesicles (sEVs): the next step for sEV clinical applications Zélia Silva - Oxidative stress and inflammatory response of fibroblasts exposed to chlorpyrifos |
Advances in ToxicologyChair: Judite Vieira |
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12:00-12:45 |
Vera Costa - Cardio-oncology: something old, something new, something bowered and something blue João Lopes - Use of lipid vesicles for revealing the potential contribution of cytochrome c in the metabolism of environmental toxicants Inês Rodrigues - Effects of atmospheric particulate matter (PM) in exposed Mytilus galloprovincialis |
12:45-13:15 |
Félix Carvalho - Toxicology of the XXI century |
13:15-14:15 |
Lunch |
14:15-15:15 |
Special Session: Environmental Health and Human Toxicology - from the Lab to the FieldChairs: Dorinda Silva, Silvia Scaglione and Ethel Eljarrat |
MetallodrugsChair: Manuel Aureliano |
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15:15-15:45 |
Ignacio León - Finding new molecular targets of Copper(II) complexes on triple negative breast cancer cells using mass spectrometry-based quantitative proteomics |
15:45-15:55 |
Coffee Break |
15:55-16:20 |
Ricardo Lagoa - The growth curve method to rapidly derive the antibacterial potential of polyoxovanadates Diana Pereira - Silver-based nanoparticles as powerful pathogen-killing agents |
16:20-16:50 |
Debbie C. Crans - Potential applications of vanadium-based anticancer drugs for intratumoral injections |
16:50-17:00 |
Closing Remarks |
Registration
Participation in the Meeting is considered final only when the registration fee has been paid. The number of participants is limited: once the number of paid registrations reaches the maximum number of participants, unpaid registrations will be cancelled.
Please note that, in order to define the scientific Program in due time, at least one registration by anyone of the authors, denoted as Covering Author, is required to cover the presentation and publication of any accepted abstract. Covering Author registration deadline is 8 July 2022. Your abstract will be withdrawn if your registration is not complete by this date.
Authors with multiple contributions: Please note that one author registration will cover only ONE accepted contribution.
Conference Paper - Publication Fees
As indicated in the Instructions for Authors, accepted manuscripts can optionally be published in a dedicated volume of the Journal Medical Sciences Forum. Note that publication of the accepted manuscripts will only be available for those authors that have paid the relevant publication charges. If you wish to publish your conference paper in the dedicated volume, please select one of the following Registration Extras* when placing your registration order:
- Publication of Conference Paper (1 - 4 pages): 30 Euro
- Publication of Conference Paper (1 - 9 pages): 60 Euro
Support to participation
The Organization can support some fees (Registration or Paper publication) on request until 28th July. Young students and participants from Low/Lower-Middle income countries (participant affiliation) can apply. After Abstract submission and before registration, contact the Organization: Dra. Dorinda Silva (mbstoxleiria@gmail.com).
Registration and Invoicing Contact Person
Click on "Event Registration" to register in the Meeting. The extra fees for publication of your Conference Paper in Medical Sciences Forum will appear to select as optional extras. Please do not hesitate to contact Ms. Carmen Ruiz (carmen.ruiz@mdpi.com) for any query regarding your registration order or invoice related to the event.
Regular Until 31st August 2022 |
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Invited Speakers and Chairs | Free |
General Attendance | 90.00 EUR |
Payment methods
Wire transfer, Credit card
Instructions for Authors
The Meeting offers flexible opportunities to present and publish your work.
Submissions should be done by the authors online by registering at www.sciforum.net, and using the "Start New Submission" function once logged into the system. There is no limit of abstracts submitted by one author, but one registration will cover only ONE accepted contribution.
- Researchers interested in participating at the Meeting can submit their abstract online on this website until 30 June 2022. The abstract submitted should be in English. Late abstract submissions might also be accepted according to the limit of participants and the program planning.
- The Scientific Committee will evaluate the abstracts received and all the authors will be notified about the acceptance of their works before 30 June 2022.
- If the abstract is accepted for the Meeting, the authors will be asked to upload a "Full file" of their work (a Manuscript and/or a Slide presentation or a Video), up to the deadline of 31 August 2022. These Full files are optional, but offer the possibility to all authors to show more of their works.
- Following assessment by the Scientific Committee, you will be notified by 11 July 2022 whether your contribution has also been accepted for Oral Communication at the event. Late abstract submissions will be considered according to the program planning.
- The Abstracts and the uploaded Full files will be available at this website for discussion during the time of the Meeting, 8–9 September 2022.
- Optionally, authors can publish their Manuscripts as Conference Papers in a dedicated volume of the Journal Medical Sciences Forum. Note that publication of the accepted manuscripts requires payment of publication charges. The Papers will be published with a DOI and the authors retain the copyright of the work. Please refer to the below Manuscript instructions and the above Registration information for further details.
After the Meeting, participants are encouraged to submit their full work to the Special Issue of the journal International Journal of Molecular Sciences associated to the Meeting. These articles will be offered a discount over the general APC of the Journal.
Note that the submission to the Special Issue is independent from the Conference Papers and will follow the usual process of the Journal, including peer-review, etc.
Manuscript Preparation
Manuscripts for the Meeting and publication in Medical Sciences Forum must have the following organization:
First page:
- Title
- Full author names
- Affiliations (including full postal address) and authors' e-mail addresses (institutional addresses preferred)
- Abstract (200–300 words)
- Keywords
Sections:
- Introduction
- Methods
- Results and Discussion
- Conclusions
- (Acknowledgements)
- References
Manuscripts should be prepared and submitted as MS Word files (download the word template here). The publication format will be PDF. The manuscript should be at least 1 page and should not exceed 9 pages (incl. figures, tables and references).
For publication of the Manuscript in Medical Sciences Forum, please carefully read the rules outlined in the 'Instructions for Authors' on the journal website and ensure that your manuscript submission adheres to these guidelines. The processing charges for publication in this journal depend on the length of the manuscript, 30 euros (1-4 pages) or 60 euros (5-9 pages). The papers will be published with a DOI, in a volume of the journal dedicated to the Meeting, using a CC BY 4.0 license meaning the authors retain copyright and the text can be reused.
Presentation Slides or Video
Authors are encouraged to prepare a collection of slides in PowerPoint or similar software or produce a Video, to be displayed online along with or alternatively to the manuscript. Authors that wish to present only the slides or the video, i.e., without a proceedings paper, can do it too.
Slides, if available, will be displayed directly in the website using the proprietary slides viewer at Sciforum.net. Slides can be prepared in the same way as for any traditional conference where research results are presented. Slides should be converted to PDF format before submission so that our process can easily and automatically convert them for online display. Videos should have a maximum size of 250 Mb and should be prepared in one of the following formats: mp4, webm or ogg.
Potential Conflict of Interest
It is the authors' responsibility to identify and declare any personal circumstances or interests that may be perceived as inappropriately influencing the representation or interpretation of clinical research. If there is no conflict, please state here "The authors declare no conflict of interest." This should be conveyed in a separate "Conflict of Interest" statement preceding the "Acknowledgments" and "References" sections at the end of the manuscript. Financial support for the study must be fully disclosed under "Acknowledgments" section.
Copyright
MDPI, the publisher of the Sciforum.net platform, is an open access publisher. We believe that authors should retain the copyright to their scholarly works. Hence, by submitting a Conference paper to this conference, you retain the copyright of your paper, but you grant MDPI the non-exclusive right to publish this paper online on the Sciforum.net platform. This means you can easily submit your paper to any scientific journal at a later stage and transfer the copyright to its publisher (if required by that publisher).
List of accepted submissions (12)
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sciforum-061749 |
Use of lipid vesicles for revealing the potential contribution of cytochrome c in the metabolism of environmental toxicants |
, , , | N/A |
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Cytochrome c (Cc) is well-known as an electron carrier at mitochondria, but the hemeprotein can also catalyze peroxidase-like reactions. Although it was previously shown that Cc oxidizes aromatic hydrocarbons and heterocyclic compounds, the reported catalytic efficiencies were low. However, Cc interaction with some lipids increases its peroxidase activity. On this basis, we tested the hypothesis that lipid membranes could improve the study of Cc role in the metabolism of environmental toxicants. The compounds studied were methyl orange (MO), an azo dye model, and the polycyclic aromatic hydrocarbons (PAHs) benzo[b]fluoranthene and benzo[a]pyrene (BaP). The biotransformation assays were carried out at pH 7.0, with Cc from horse heart at 0.01 mg/mL, in the presence of H2O2 at 100 microM. Membranes were prepared as small unilamellar vesicles composed of phosphatidylcholine (PC) or mixtures of PC with cardiolipin (CL) at a 4:1 molar ratio. The transformation of MO was monitored by UV-Vis spectrophotometry and the PAHs measured by HPLC. The results showed that Cc, in the presence of H2O2, slowly transformed MO. The presence of the PC vesicles (200 microM) in the reaction media did not significantly affect the transformation kinetics, but the PC/CL vesicles clearly increased the rate of MO decolorization by Cc. In the case of the PAHs, the Cc-mediated oxidation was almost imperceptible (<15%), in spite of the high compounds’ concentrations used in the assays (1 mg/L). Nevertheless, by including CL vesicles in the assay media, the transformation became evident from the decrease observed in the BaP and BbF chromatographic peaks and by the emergence of reaction products peaks in the chromatograms. Indeed, in the presence of these vesicles, BaP oxidation reached 71±2% after 24 h incubations. In conclusion, lipid membranes can be employed to further investigate the potential participation of Cc in the metabolism of important toxicants. |
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sciforum-062121 |
Potential Applications of Vanadium-Based Anticancer Drugs for Intratumoral Injections |
, , , | N/A |
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Injections of highly cytotoxic or immunomodulating drugs directly into the tumor, is a procedure that is increasingly applied in the clinic. Established Pt-based drugs are used in numerous clinical trials using this administration method. Intratumoral administration may also be advantageous for less stable anticancer metal complexes that fail administration by the standard intravenous route. Particularly, hydrophobic metal-containing complexes are taken up rapidly into cancer cells and cause cell death, while the release of their much less toxic decomposition products into the blood has low overall systemic toxicity and, in some cases may even be beneficial. This concept was originally proposed for hydrophobic vanadium(V) (V(V)) complexes with sterically hindered organic ligands, non-innocent Schiff base V(V) catecholato complexes. Several of these classes of complexes were investigated exhibiting a distinct pattern in their potencies against cancer. These complexes were reactive but sufficiently stable and hence survive under physiological conditions and react with the tumor. This strategy can potentially be applied to other metal complexes, such as titanium(IV), gallium(III) and ruthenium(III) complexes, some of which were previously unsuccessful in human clinical trials when administered via intravenous injections. The intratumoral injection potencies can furthermore be improved by delivery of nanocarrier formulations of potent but unstable metal complexes. |
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sciforum-062418 | The cytotoxicity of phorbol 12- myristate 13-acetate and lipopolysaccharide on THP-1 cells and optimized differentiation protocol | , , | N/A |
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In order to evaluate the immunomodulatory potential of novel monofloral Irish honeys, THP-1 monocyte-derived macrophages provided a suitable cell-based model. THP-1 cells can be differentiated to macrophages using phorbol-12-myristate-13-acetate (PMA). Differentiated cells are then challenged with lipopolysaccharide (LPS) to stimulate the inflammatory cascade. Few studies on the cytotoxic concentrations of these two compounds on THP-1 cells are published. Therefore, the viability of treated THP-1 cells was initially evaluated using trypan blue dye exclusion (PMA), the resazurin assay (LPS), and propidium iodide staining. Furthermore, research to date suggests concentrations ranging from 100 ng/ml down to 15 ng/ml (Lund et al., 2016) and 5 ng/ml (Park et al., 2007) PMA are sufficient for THP-1 differentiation. Consequently, the differentiation potential of this sub-cytotoxic PMA concentration range was also evaluated using flow cytometric detection of the macrophage-specific CD-14 cell surface marker. The highest concentration of PMA (1 µg/ml) evaluated with the trypan blue exclusion assay caused ~20% cell death. Flow cytometry results indicated CD14 percentage for THP-1 cells exposed to 100ng/ml PMA for 48 hours (~14.63%, SD ± 3.94) were lower than 15ng/ml (~43.41%, SD ± 5.46) and 5ng/ml (~38.36%, SD ±13.12). No substantial time-dependent difference for these concentrations was observed following 48 versus 72-hour exposure. The highest LPS concentration, 100-fold higher than concentrations used in the literature, caused ~29.21% (resazurin assay) and ~25.76% (PI staining) cell death in differentiated THP-1 cells. In summary, the differentiation capacity of THP-1 cells, and the differentiation ability of the test compounds require cytotoxicity assays to be chosen carefully. Important variables affecting assay outcomes include phenotypic differences between untreated control cells (monocytes) versus treated monocyte-derived macrophages in terms of metabolic and pinocytosis rates. |
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sciforum-061613 | Synthetic membranes as an alternative model to animal skin to investigate dermal permeation of chlorpyrifos | , | N/A |
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Dermal exposure to air pollutants is gaining increasing interest at toxicological level. Chlorpyrifos is a broad-spectrum pesticide used for treatments revised by authorities as representing a risk for human health. Few studies investigated the permeation of chlorpyrifos through skin either by using ex vivo animal skin or human skin, but this practice urges for a more ethical mode of action in scientific research. The purpose of this study was to assess two synthetic membranes as non-animal alternatives to study the dermal permeation of chlorpyrifos for human health risk assessment. Permeation assays were performed using silicone and Strat-M® membranes mounted on Franz cells with different receptor compositions. Sampling was conducted for HPLC quantification. The permeation kinetic fluxes obtained for the pesticide were calculated and compared to those reported in the literature for in vitro and in vivo human skin. For both membranes, faster permeation of chlorpyrifos was observed for the highest concentration of ethanol used in the receptor fluid. Therefore, after 8h – work shift time - there was also a higher concentration of the pesticide that permeated both membranes. Regarding the time lag (Tlag), values inferior to 1h were obtained for both membranes and for receptor conditions containing ethanol between 10 and 50%. Adopting these conditions, the flux values obtained for silicone and Strat-M® membranes were 1.5 ± 0.1 and 1.9 ± 1.2 µg cm-2h-1. Importantly, the flux and the Tlag values obtained are close to those reported in human skin studies, supporting the use of these membranes as non-animal systems mimicking the permeation of chlorpyrifos through human skin. Up to our knowledge, this is the first study where alternative synthetic membranes are used achieving values close to those found for in vivo human exposure to a pesticide, validating experimental conditions to be considered in this research field. |
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sciforum-063355 | Targeting immune-mediated responses to tackle GNE myopathy | , , | N/A |
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GNE myopathy is an ultra-rare congenital disorder of glycosylation (CDG) that manifests in early adulthood causing progressive distal muscle atrophy and weakness. GNE-CDG results from mutations in the GNE gene, leading to decreased sialic acid (Sia) production [1]. Although hyposialylation has been presumed to be the main cause of GNE-CDG, its pathomechanism may not be exclusively linked to the impaired Sia pathway [2]. Our purpose is to explore cellular and molecular mechanisms that may contribute to GNE-CDG as means of identifying alternative pharmacological targets. Although immune-mediated responses are not common in GNE-CDG, inflammatory cell infiltration with increased expression of major histocompatibility complex class I (MHC-I) is occasionally reported in muscle biopsies of early-stage GNE-CDG patients [3]. A GNE knockout (KO) cell model was used to evaluate if GNE mutations affect the expression of MHC-I. The results point to higher expression of MHC-I on the surface of GNE-CDG cells. When the GNE KO cells were supplemented with N-acetylmannosamine (ManNAc) and ManNAc-6-phosphate (ManNAc-6-P), intermediates in the Sia biosynthesis, we observed a Sia increase, and a reduction in MHC-I staining. These findings support the hypothesis that Sia content modulates the presence and stability of the MHC-I complex, as previously reported by us [4], and the involvement of a cytotoxic immune response initiated via MHC-I presentation. Further work is being conducted to better characterize this immunological link, which may contribute to identifying new biomarkers that facilitate GNE-CDG diagnosis and novel therapeutic approaches. Acknowledgements: UIDP/04378/2020 and UIDB/04378/2020 (UCIBIO), LA/P/0140/2020 (i4HB), and EJP RD COFUND-EJP N 825575 (EJPRD/0001/2020). References: [1] doi:10.1186/s13023-018-0802-x. [2] doi:10.1016/j.bbrc.2004.12.157. [3] doi:10.1016/S0960-8966(03)00140-8. [4] doi: 10.3390/pharmaceutics12030249. |
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TAR. Targets
Target identification, mechanisms of action, network pharma/toxicology, bioactive compounds, drug resistance, etc.
Session Chairs
Ricardo Lagoa, Anupam Bishayee and Félix Carvalho
MAT. Materials
Nanoparticles toxicology, biomaterials, drug delivery systems, fabrication techniques, etc.
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Mário Diniz
IMMU. Immunotherapeutics and Immunotoxicology
Biological drugs, immunotoxicology, glycodrugs, cell therapies, etc.
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Paula Videira
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BSD. Biosensors and Biodevices
Biosensors, biodevices, in situ applications, biofabrication techniques, generation of functional tissues, etc.
Session Chair
Victor C. Diculescu
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BB. Biomimicking and Biobarriers
Cell culture systems, non-animal and human-relevant methods, tissue barriers, biological membranes, etc
Session Chairs
Maria João Moreno and Silvia Scaglione
NAMT. Nano- and Metallo-drugs
Nanoformulations testing, nanobiotechnology, design of metallodrugs, etc.
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M. Aureliano