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Thales, P, Vale TM, Dias RJ, Lourenço JM.  Submitted.  Empowering a Relational Database with Lazy State Determination.
2025
Leitão, F, Galrito D, Branco LC, Cruz H, Branco PS.  2025.  Electrochemical studies of Benzoquinone, Hydrobenzoquinone, Diphenoquinone, and Hydrodiphenoquinone-Based Compounds. Electrochem. Sci. Adv. :e70006.
2024
Alexandre, D, Fernandes {AR}, Baptista {PV}, Cruz C.  2024.  Evaluation of miR-155 silencing using a molecular beacon in human lung adenocarcinoma cell line, jul. Talanta. 274: Elsevier Abstract

Lung cancer (LC) is a leading cause of global cancer-related deaths, highlighting the development of innovative methods for biomarker detection improving the early diagnostics. microRNAs (miRs) alterations are known to be involved in the initiation and progression of human cancers and can act as biomarkers for diagnostics and treatment. Herein, we develop the application of molecular beacon (MB) technology to monitor miR-155-3p expression in human lung adenocarcinoma A549 cells without complementary DNA synthesis, amplification, or expensive reagents. Furthermore, we produced gold nanoparticles (AuNPs) for delivering antisense oligonucleotides into A549 cells to reduce miR-155-3p expression, which was subsequently detectable using the MB. The MB was designed and structural characterized by Förster Resonance Energy Transfer (FRET)-melting, Circular Dichroism (CD), Nuclear magnetic resonance (NMR), and fluorometric experiments, and then the hybridization conditions were optimized for an in vitro approach involving the detection of miR-155-3p in total RNA extracted from A549 cell line. The expression profile of miR-155-3p was obtained by RT-qPCR. The results demonstrated that MB was properly designed and showed efficacy in targeting miR-155-3p. Furthermore, a limit of detection down to nanomolar concentration was achieved and the specificity of the biosensor was proved. Moreover, the self-assembly of ASOs with AuNPs exhibited exceptional target specificity, effectively silencing miR-155-3p. Notably, compared to lipid-based transfection agent, AuNPs displayed superior silencing efficiency. We highlighted the ability of MB to detect changes in the target gene expression after gene silencing. Overall, this innovative approach represents a promising tool for detecting various biomarkers at the same time, with potential applications in clinical settings.

{Franco Machado}, J, Cordeiro S, Duarte {JN }, Costa {PJ }, Mendes {PJ }, Garcia {MH}, Baptista {PV}, Fernandes {AR}, Morais {TS }.  2024.  Exploiting Co(III)-Cyclopentadienyl Complexes To Develop Anticancer Agents, apr. Inorganic Chemistry. 63:5783–5804., Number 13: ACS - American Chemical Society Abstract

In recent years, organometallic complexes have attracted much attention as anticancer therapeutics aiming at overcoming the limitations of platinum drugs that are currently marketed. Still, the development of half-sandwich organometallic cobalt complexes remains scarcely explored. Four new cobalt(III)-cyclopentadienyl complexes containing N,N-heteroaromatic bidentate, and phosphane ligands were synthesized and fully characterized by elemental analysis, spectroscopic techniques, and DFT methods. The cytotoxicity of all complexes was determined in vitro by the MTS assay in colorectal (HCT116), ovarian (A2780), and breast (MDA-MB-231 and MCF-7) human cancer cell lines and in a healthy human cell line (fibroblasts). The complexes showed high cytotoxicity in cancer cell lines, mostly due to ROS production, apoptosis, autophagy induction, and disruption of the mitochondrial membrane. Also, these complexes were shown to be nontoxic in vivo in an ex ovo chick embryo yolk sac membrane (YSM) assay.

Rippel, R, Leitão F, Georgieva MK, Mamede M, Gomes CSB, Roma-Rodrigues C, Fernandes AR, Lourenço A, Ferreira LM, Branco PS.  2024.  Exploring The Synthesis of Aminal Guanidine-Based Molecules: Synthesis of Cernumidine and Analogues, and Survey of its Anti-inflammatory Activity. New J. Chem.. 48:5247–5257.
Reigosa-Chamorro, F, Cordeiro S, Pereira T}{M, Filipe B, Baptista {PV}, Fernandes {AR}, Vila {JM }.  2024.  Effect of mono- and dinuclear thiosemicarbazone platinacycles in the proliferation of a colorectal carcinoma cell line. Dalton Transactions. : RSC - Royal Society of Chemistry Abstract

Herein, we describe the synthesis and characterization of a series of thiosemicarbazone platinacycles. Their activity towards HCT116 and A2780 cancer cell lines as well as normal fibroblasts was explored and conclusions about the influence of their structures were drawn based on the results. Ligands L1-3, tetranuclear compounds [Pt(L1-3)]4, [Pt(L1-3)(PPh3)], and [Pt(L1-L3)2{Ph2P(CH2)4PPh2}], and phosphine derivatives, were deemed unpromising owing to their lack of activity. However, mono-coordinated diphosphine complexes [Pt(L1-L3)(Ph2PCH2PPh2-P)] showed high selectivity and low IC50 values, and their antiproliferative activity was further studied. The three studied derivatives 3a, 3b and 3c showed a fast internalization of HCT116 colorectal cancer cells with similar IC50 values, which induced a depolarization of mitochondrial membrane potential, with the subsequent triggering of apoptosis and autophagy in the case of 3c. In the case of compounds 3a and 3b, cell death mechanisms (extrinsic and intrinsic apoptosis, respectively) were triggered via the induction of reactive oxygen species (ROS). The three compounds were not toxic to a chicken embryo in vivo (after 48 h), and, importantly, showed an anti-angiogenic potential after exposure to the IC50 of compounds 3a, 3b and 3c.

2023
Martins, MM, Branco PS, Ferreira LM.  2023.  Enhancing the Therapeutic Effect in Alzheimer's Disease Drugs: The role of Polypharmacology and Cholinesterase inhibitors, MAR 13. CHEMISTRYSELECT. 8, Number 10 Abstract

Alzheimer's disease (AD) is a devastating syndrome that accounts for 60-70 % of all dementia cases, putting an enormous burden on global healthcare and economy. Unfortunately, there is no cure for AD, and the currently approved drugs are limited in their effects. Given the various pathological mechanisms behind AD, the ``one-target, one-drug{''} paradigm for drug design became obsolete, and a new paradigm, polypharmacology, emerged. Consequently, a greater focus has been put towards multi-target directed ligands (MTDLs), as these can regulate several targets operating in the disease network. Parallel to that, cholinesterase inhibitors have regained popularity after decades of being considered only symptomatic agents with no disease-modifying properties. In this review, the current AD hypotheses and therapeutic targets, the concept of polypharmacology in AD pathology and the importance of cholinesterases in the pathogenesis and biochemical processes of AD are discussed, with a final overview of the current development in cholinesterase-based MTDLs.

Susnik, E, Bazzoni A, Taladriz-Blanco P, Balog S, Moreno-Echeverri {AM}, Glaubitz C, {Brito Oliveira} B, Ferreira D, {Viana Baptista} P, Petri-Fink A, Rothen-Rutishauser B.  2023.  Epidermal growth factor alters silica nanoparticle uptake and improves gold-nanoparticle-mediated gene silencing in A549 cells, jul. Frontiers in Nanotechnology. 5: Frontiers Media Abstract

Introduction: Delivery of therapeutic nanoparticles (NPs) to cancer cells represents a promising approach for biomedical applications. A key challenge for nanotechnology translation from the bench to the bedside is the low amount of administered NPs dose that effectively enters target cells. To improve NPs delivery, several studies proposed NPs conjugation with ligands, which specifically deliver NPs to target cells via receptor binding. One such example is epidermal growth factor (EGF), a peptide involved in cell signaling pathways that control cell division by binding to epidermal growth factor receptor (EGFR). However, very few studies assessed the influence of EGF present in the cell environment, on the cellular uptake of NPs. Methods: We tested if the stimulation of EGFR-expressing lung carcinomacells A549 with EGF affects the uptake of 59 nm and 422 nm silica (SiO2) NPs. Additionally, we investigated whether the uptake enhancement can be achieved with gold NPs, suitable to downregulate the expression of cancer oncogene c-MYC. Results: Our findings show that EGF binding to its receptor results in receptor autophosphorylation and initiate signaling pathways, leading to enhanced endocytosis of 59 nm SiO2 NPs, but not 422 nm SiO2 NPs. Additionally, we demonstrated an enhanced gold (Au) NPs endocytosis and subsequently a higher downregulation of c-MYC. Discussion: These findings contribute to a better understanding of NPs uptake in the presence of EGF and that is a promising approach for improved NPs delivery.

Oliveira, {BB }, Ferreira D, Fernandes {AR}, Baptista {PV}.  2023.  Engineering gold nanoparticles for molecular diagnostics and biosensing, feb. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 15, Number 1: John Wiley and Sons Inc. Abstract

Advances in nanotechnology and medical science have spurred the development of engineered nanomaterials and nanoparticles with particular focus on their applications in biomedicine. In particular, gold nanoparticles (AuNPs) have been the focus of great interest, due to their exquisite intrinsic properties, such as ease of synthesis and surface functionalization, tunable size and shape, lack of acute toxicity and favorable optical, electronic, and physicochemical features, which possess great value for application in biodetection and diagnostics purposes, including molecular sensing, photoimaging, and application under the form of portable and simple biosensors (e.g., lateral flow immunoassays that have been extensively exploited during the current COVID-19 pandemic). We shall discuss the main properties of AuNPs, their synthesis and conjugation to biorecognition moieties, and the current trends in sensing and detection in biomedicine and diagnostics. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Roma-Rodrigues, C, Fernandes {AR}, Baptista {PV}.  2023.  Exploring RAB11A Pathway to Hinder Chronic Myeloid Leukemia-Induced Angiogenesis In Vivo, feb. Pharmaceutics. 15, Number 3: MDPI AG Abstract

Neoangiogenesis is generally correlated with poor prognosis, due to the promotion of cancer cell growth, invasion and metastasis. The progression of chronic myeloid leukemia (CML) is frequently associated with an increased vascular density in bone marrow. From a molecular point of view, the small GTP-binding protein Rab11a, involved in the endosomal slow recycling pathway, has been shown to play a crucial role for the neoangiogenic process at the bone marrow of CML patients, by controlling the secretion of exosomes by CML cells, and by regulating the recycling of vascular endothelial factor receptors. The angiogenic potential of exosomes secreted by the CML cell line K562 has been previously observed using the chorioallantoic membrane (CAM) model. Herein, gold nanoparticles (AuNPs) were functionalized with an anti-RAB11A oligonucleotide (AuNP@RAB11A) to downregulate RAB11A mRNA in K562 cell line which showed a 40% silencing of the mRNA after 6 h and 14% silencing of the protein after 12 h. Then, using the in vivo CAM model, these exosomes secreted by AuNP@RAB11A incubated K562 did not present the angiogenic potential of those secreted from untreated K562 cells. These results demonstrate the relevance of Rab11 for the neoangiogenesis mediated by tumor exosomes, whose deleterious effect may be counteracted via targeted silencing of these crucial genes; thus, decreasing the number of pro-tumoral exosomes at the tumor microenvironment.

Moniz, M, Rafique A, Carmo J, Marques A, Ferreira I, Batista A.  2023.  Electrospray of PEDOT:PSS: Enhancing the Performance of Solid-State Fiber-Shaped Supercapacitors, 3-6 July. 16th International Symposium on Flexible Organic Electronics. , Thessaloniki, Greece
Rafique, A, Moniz M, Carmo J, Marques A, Ferreira I, Baptista A.  2023.  Exfoliated carbon yarn structure for highly stable flexible supercapacitors electrodes in simulated sweat solutions, 3-6 April. XXI Congresso da Sociedade Portuguesa de Materiais and XII International Symposium on Materials. , Guimarães
Silva, JM, Cerofolini L, Carvalho AL, Ravera E, Fragai M, Parigi G, Macedo AL, Geraldes CFGC, Luchinat C.  2023.  Elucidating the concentration-dependent effects of thiocyanate binding to carbonic anhydrase, 2023. 244:112222. AbstractWebsite

Many proteins naturally carry metal centers, with a large share of them being in the active sites of several enzymes. Paramagnetic effects are a powerful source of structural information and, therefore, if the native metal is paramagnetic, or it can be functionally substituted with a paramagnetic one, paramagnetic effects can be used to study the metal sites, as well as the overall structure of the protein. One notable example is cobalt(II) substitution for zinc(II) in carbonic anhydrase. In this manuscript we investigate the effects of sodium thiocyanate on the chemical environment of the metal ion of the human carbonic anhydrase II. The electron paramagnetic resonance (EPR) titration of the cobalt(II) protein with thiocyanate shows that the EPR spectrum changes from A-type to C-type on passing from 1:1 to 1:1000-fold ligand excess. This indicates the occurrence of a change in the electronic structure, which may reflect a sizable change in the metal coordination environment in turn caused by a modification of the frozen solvent glass. However, paramagnetic nuclear magnetic resonance (NMR) data indicate that the metal coordination cage remains unperturbed even in 1:1000-fold ligand excess. This result proves that the C-type EPR spectrum observed at large ligand concentration should be ascribed to the low temperature at which EPR measurements are performed, which impacts on the structure of the protein when it is destabilized by a high concentration of a chaotropic agent.

Moniz, M, Rafique A, Marques A, Ferreira I, Baptista A, Carmo J, Oliveira JP.  2023.  Electrospray Deposition of PEDOT:PSS on Carbon Yarn Electrodes for Solid-State Flexible Supercapacitors. ACS Applied Materials & Interfaces 2023. 15
Portela, PC, Morgado L, Silva MA, Denkhaus L, Einsle O, Salgueiro CA.  2023.  Exploring oxidative stress pathways in Geobacter sulfurreducens: the redox network between MacA peroxidase and triheme periplasmic cytochromes. Frontiers in Microbiology. 14 AbstractWebsite

The recent reclassification of the strict anaerobe Geobacter sulfurreducens bacterium as aerotolerant brought attention for oxidative stress protection pathways. Although the electron transfer pathways for oxygen detoxification are not well established, evidence was obtained for the formation of a redox complex between the periplasmic triheme cytochrome PpcA and the diheme cytochrome peroxidase MacA. In the latter, the reduction of the high-potential heme triggers a conformational change that displaces the axial histidine of the low-potential heme with peroxidase activity. More recently, a possible involvement of the triheme periplasmic cytochrome family (PpcA-E) in the protection from oxidative stress in G. sulfurreducens was suggested. To evaluate this hypothesis, we investigated the electron transfer reaction and the biomolecular interaction between each PpcA-E cytochrome and MacA. Using a newly developed method that relies on the different NMR spectral signatures of the heme proteins, we directly monitored the electron transfer reaction from reduced PpcA-E cytochromes to oxidized MacA. The results obtained showed a complete electron transfer from the cytochromes to the high-potential heme of MacA. This highlights PpcA-E cytochromes’ efficient role in providing the necessary reducing power to mitigate oxidative stress situations, hence contributing to a better knowledge of oxidative stress protection pathways in G. sulfurreducens.

2022
Sarrato, J, Pinto AL, Cruz H, Jordao N, Malta G, Branco PS, Carlos Lima J, Branco LC.  2022.  Effect of Iodide-Based Organic Salts and Ionic Liquid Additives in Dye-Sensitized Solar Cell Performance, SEP. NANOMATERIALS. 12, Number 17 Abstract
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Rodrigo, {AP }, Lopes {AC}, Pereira R, Anjo {SI }, Manadas B, Grosso {AR }, Baptista {PV}, Fernandes {AR}, Costa {PM }.  2022.  Endogenous Fluorescent Proteins in the Mucus of an Intertidal Polychaeta: Clues for Biotechnology, mar. Marine Drugs. 20, Number 4: MDPI - Multidisciplinary Digital Publishing Institute Abstract

The vast ocean holds many unexplored organisms with unique adaptive features that enable them to thrive in their environment. The secretion of fluorescent proteins is one of them, with reports on the presence of such compounds in marine annelids being scarce. The intertidal Eulalia sp. is an example. The worm secretes copious amounts of mucus, that when purified and concentrated extracts, yield strong fluorescence under UV light. Emission has two main maxima, at 400 nm and at 500 nm, with the latter responsible for the blue–greenish fluorescence. Combining proteomics and transcriptomics techniques, we identified ubiquitin, peroxiredoxin, and 14-3-3 protein as key elements in the mucus. Fluorescence was found to be mainly modulated by redox status and pH, being consistently upheld in extracts prepared in Tris-HCl buffer with reducing agent at pH 7 and excited at 330 nm. One of the proteins associated with the fluorescent signal was localized in secretory cells in the pharynx. The results indicate that the secretion of fluorescent proteinaceous complexes can be an important defense against UV for this dweller. Additionally, the internalization of fluorescent complexes by ovarian cancer cells and modulation of fluorescence of redox status bears important considerations for biotechnological application of mucus components as markers.

Isufi, B, Marchão C, Marreiros R, Ramos AP.  2022.  Experimental Investigation on the Behaviour of Hybrid HPFRC Flat Slabs, June 2022. fib Congress 2022, Oslo. , Oslomonotonicoslo.pdf
Barbosa, DJ, Capela JP, Ferreira LM, Branco PS, Fernandes E, de Bastos ML, Carvalho F.  2022.  Ecstasy metabolites and monoamine neurotransmitters upshift the Na+/K+ ATPase activity in mouse brain synaptosomes, DEC. ARCHIVES OF TOXICOLOGY. 96:3279-3290., Number 12 Abstract
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Thales, P, Vale TM, Dias RJ, Lourenço JM.  2022.  Empowering a Relational Database with LSD: Lazy State Determination, 8-9 Sep.. Atas do INForum 2022. , Atas INForum 2022. Instituto Politécnico da Guardatv22_-_lsd-sql.pdf
Martins, RA, Carlos E, Deuermeier J, Pereira ME, Martins R, Fortunato E, Kiazadeh A.  2022.  Emergent solution based IGZO memristor towards neuromorphic applications, 2022///. Journal of Materials Chemistry C. 10(6):1991-1998.: Royal Society of Chemistry AbstractWebsite

Solution-based memristors are emergent devices, due to their potential in electrical performance for neuromorphic computing combined with simple and cheap fabrication processes.

Morgado, L, Salgueiro CA.  2022.  Elucidation of complex respiratory chains: a straightforward strategy to monitor electron transfer between cytochromes, 02. Metallomics. AbstractWebsite

{Cytochromes are electron transfer proteins essential in various biological systems, playing crucial roles in the respiratory chains of bacteria. These proteins are particularly abundant in electrogenic microorganisms and are responsible for the efficient delivery of electrons to the cells’ exterior. The capability of sending electron outside the cells open new avenues to be explored for emerging biotechnological applications in bioremediation, microbial electrosynthesis and bioenergy fields. To develop these applications, it is critical to identify the different redox partners and elucidate the stepwise electron transfer along the respiratory paths. However, investigating direct electron transfer events between proteins with identical features in nearly all spectroscopic techniques is extremely challenging. NMR spectroscopy offers the possibility to overcome this difficulty by analysing the alterations of the spectral signatures of each protein caused by electron exchange events. The uncrowded NMR spectral regions containing the heme resonances of the cytochromes display unique and distinct signatures in the reduced and oxidized states, which can be explored to monitor electron transfer within the redox complex. In this study, we present a strategy for a fast and straightforward monitorization of electron transfer between c-type cytochromes, using as model a triheme periplasmic cytochrome (PpcA) and a membrane associated monoheme cytochrome (OmcF) from the electrogenic bacterium Geobacter sulfurreducens. The comparison between the 1D 1H NMR spectra obtained for samples containing the two cytochromes and for samples containing the individual proteins clearly demonstrated a unidirectional electron transfer within the redox complex. This strategy provides a simple and straightforward means to elucidate complex biologic respiratory electron transfer chains.}

Rajnak, M, Franko M, Paulovicova K, Karpets M, Parekh K, Upadhyay R, Kurimsky J, Dolnik B, Cimbala R, Havran P, Timko M, Kopcansky P.  2022.  Effect of ferrofluid magnetization on transformer temperature rise. Journal of Physics D: Applied Physics. 55(34)
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