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  1. Article: L-Thyroxine and L-thyroxine-based antimicrobials against Streptococcus pneumoniae and other Gram-positive bacteria.

    Galano-Frutos, Juan José / Maity, Ritwik / Iguarbe, Verónica / Aínsa, José Antonio / Velázquez-Campoy, Adrián / Schaible, Ulrich E / Mamat, Uwe / Sancho, Javier

    Heliyon

    2024  Volume 10, Issue 7, Page(s) e27982

    Abstract: Objectives: The rise of antibiotic-resistant : Method: We performed a high-throughput screening of a library of compounds approved for use in humans, complemented with ITC assays on purified : Results: Human l-thyroxine binds to : Conclusions: ... ...

    Abstract Objectives: The rise of antibiotic-resistant
    Method: We performed a high-throughput screening of a library of compounds approved for use in humans, complemented with ITC assays on purified
    Results: Human l-thyroxine binds to
    Conclusions: l-thyroxine derivatives targeting bacterial flavodoxins represent a new and promising class of antimicrobials.
    Language English
    Publishing date 2024-03-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2024.e27982
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Measuring Efflux and Permeability in Mycobacteria.

    Rodrigues, Liliana / Aínsa, José A / Viveiros, Miguel

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2314, Page(s) 231–245

    Abstract: Mycobacteria are intrinsically resistant to most antimicrobials, which is generally attributed to the impermeability of their cell wall that considerably limits drug uptake. Moreover, like in other pathogenic bacteria, active efflux systems have been ... ...

    Abstract Mycobacteria are intrinsically resistant to most antimicrobials, which is generally attributed to the impermeability of their cell wall that considerably limits drug uptake. Moreover, like in other pathogenic bacteria, active efflux systems have been widely characterized from diverse mycobacterial species in laboratory conditions, showing that they can promote resistance by extruding noxious compounds prior to their reaching their intended targets. Therefore, the intracellular concentration of a given compound is determined by the balance between permeability, influx, and efflux.Given the urgent need to discover and develop novel antimycobacterial compounds in order to design effective therapeutic strategies, the contributions to drug resistance made by the controlled permeability of the cell wall and the increased activity of efflux pumps must be determined. In this chapter, we will describe a method that allows (1) the measuring of permeability and the quantification of general efflux activity of mycobacteria, by the study of the transport (influx and efflux) of fluorescent compounds, such as ethidium bromide; and (2) the screening of compounds in search of agents that increase the permeability of the cell wall and efflux inhibitors that could restore the effectiveness of antimicrobials that are subject to efflux.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/metabolism ; Biological Transport ; Cell Membrane Permeability ; Drug Resistance, Multiple, Bacterial ; Ethidium/metabolism ; Fluorescent Dyes/metabolism ; Fluorometry/methods ; Microbial Sensitivity Tests ; Mycobacterium/drug effects ; Mycobacterium/growth & development ; Mycobacterium/metabolism
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; Fluorescent Dyes ; Ethidium (EN464416SI)
    Language English
    Publishing date 2021-07-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1460-0_9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Assessing the influence of small structural modifications in simple DNA-based nanostructures on their role as drug nanocarriers.

    Postigo, Alejandro / Martínez-Vicente, Pablo / Baumann, Kevin N / Del Barrio, Jesús / Hernández-Ainsa, Silvia

    Biomaterials science

    2024  Volume 12, Issue 6, Page(s) 1549–1557

    Abstract: DNA nanotechnology leverages Watson-Crick-Franklin base-pairing interactions to build complex DNA-based nanostructures (DNS). Due to DNA specific self-assembly properties, DNS can be designed with a total control of their architecture, which has been ... ...

    Abstract DNA nanotechnology leverages Watson-Crick-Franklin base-pairing interactions to build complex DNA-based nanostructures (DNS). Due to DNA specific self-assembly properties, DNS can be designed with a total control of their architecture, which has been demonstrated to have an impact on the overall DNS features. Indeed, structural properties such as the shape, size and flexibility of DNS can influence their biostability as well as their ability to internalise into cells. We present here two series of simple DNS with small and precise variations related to their length or flexibility and study the influence that these structural changes have on their overall properties as drug nanocarriers. Results indicate that shorter and more flexible DNS present higher stability towards nuclease degradation. These structural changes also have a certain effect on their cell internalisation ability and drug release rate. Consequently, drug-loaded DNS cytotoxicity varies according to the design, with lower cell viability values obtained in the DNS exhibiting faster drug release and larger cell interaction rates. In summary, small changes in the structure of simple DNS can have an influence on their overall capabilities as drug nanocarriers. The effects reported here could guide the design of simple DNS for future therapeutic uses.
    MeSH term(s) Nanostructures/chemistry ; DNA/chemistry ; Nanotechnology/methods ; Cell Survival
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2024-03-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2693928-9
    ISSN 2047-4849 ; 2047-4830
    ISSN (online) 2047-4849
    ISSN 2047-4830
    DOI 10.1039/d3bm01987j
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Antimicrobial combinations against

    Beyria, Lilha / Gourbeyre, Ophelie / Salillas, Sandra / Mahía, Alejandro / Díaz de Villegas, María Dolores / Aínsa, José Antonio / Sancho, Javier / Bousquet-Mélou, Alain / Ferran, Aude A

    Microbiology spectrum

    2023  Volume 12, Issue 1, Page(s) e0262323

    Abstract: Importance: The antimicrobial resistance ... ...

    Abstract Importance: The antimicrobial resistance of
    MeSH term(s) Humans ; Flavodoxin/metabolism ; Helicobacter pylori/metabolism ; Anti-Infective Agents/pharmacology ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Helicobacter Infections/drug therapy ; Helicobacter Infections/microbiology
    Chemical Substances Flavodoxin ; Anti-Infective Agents ; Anti-Bacterial Agents
    Language English
    Publishing date 2023-12-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.02623-23
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  5. Article ; Online: Synthesis and biological activity of dehydrophos derivatives.

    Jiménez-Andreu, M Mercedes / Lucía Quintana, Ainhoa / Aínsa, José A / Sayago, Francisco J / Cativiela, Carlos

    Organic & biomolecular chemistry

    2019  Volume 17, Issue 5, Page(s) 1097–1112

    Abstract: The synthesis of dehydrophos derivatives featuring modified peptide chains, characterized by the presence of substituents in the vinyl moiety, or possessing a phosphonic acid monoalkyl ester other than the monomethyl ester one, has been accomplished by a ...

    Abstract The synthesis of dehydrophos derivatives featuring modified peptide chains, characterized by the presence of substituents in the vinyl moiety, or possessing a phosphonic acid monoalkyl ester other than the monomethyl ester one, has been accomplished by a versatile procedure based on Horner-Wadsworth-Emmons olefination with suitable aldehydes and on the selective hydrolysis of the dialkyl phosphonate group. Such derivatives have been tested against a series of bacterial strains, using the naturally occurring peptide, dehydrophos, for comparison. Thus, the effects of the aforementioned structural variations on antimicrobial activity have been studied.
    MeSH term(s) Aldehydes/chemistry ; Alkenes/chemistry ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Gram-Negative Bacteria/drug effects ; Gram-Positive Bacteria/drug effects ; Hydrolysis ; Microbial Sensitivity Tests ; Organophosphorus Compounds/chemical synthesis ; Organophosphorus Compounds/chemistry ; Organophosphorus Compounds/pharmacology ; Peptides/chemistry ; Protein Conformation ; Stereoisomerism
    Chemical Substances Aldehydes ; Alkenes ; Anti-Bacterial Agents ; Organophosphorus Compounds ; Peptides
    Language English
    Publishing date 2019-01-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2097583-1
    ISSN 1477-0539 ; 1477-0520
    ISSN (online) 1477-0539
    ISSN 1477-0520
    DOI 10.1039/c8ob03079k
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Influence of Seaweeds on the Quality of Pasta as a Plant-Based Innovative Food.

    Ainsa, Andrea / Honrado, Adrián / Marquina, Pedro / Beltrán, José A / Calanche, Juan

    Foods (Basel, Switzerland)

    2022  Volume 11, Issue 16

    Abstract: This study evaluated the effect of the incorporation of seaweed on the physicochemical and technological quality of pasta. For this purpose, enriched wheat pastas from different seaweeds (sea lettuce- ...

    Abstract This study evaluated the effect of the incorporation of seaweed on the physicochemical and technological quality of pasta. For this purpose, enriched wheat pastas from different seaweeds (sea lettuce-
    Language English
    Publishing date 2022-08-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704223-6
    ISSN 2304-8158
    ISSN 2304-8158
    DOI 10.3390/foods11162525
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  7. Article ; Online: How can nanoparticles contribute to antituberculosis therapy?

    Costa-Gouveia, Joana / Aínsa, José A / Brodin, Priscille / Lucía, Ainhoa

    Drug discovery today

    2017  Volume 22, Issue 3, Page(s) 600–607

    Abstract: Therapeutic approaches using nanoparticles are being successfully used in foods and in several fields of medicine, including infectious diseases. Regarding tuberculosis (TB) treatment, nanoparticles can be a useful strategy for two distinct applications: ...

    Abstract Therapeutic approaches using nanoparticles are being successfully used in foods and in several fields of medicine, including infectious diseases. Regarding tuberculosis (TB) treatment, nanoparticles can be a useful strategy for two distinct applications: (i) for their intrinsic antimycobacterial activity; (ii) as vehicles for known antitubercular drugs to allow reduction of dose- and drug-associated side-effects and administration via user-friendly administration routes such as pulmonary or oral ones. Promising results were obtained in vitro and in animal Mycobacterium tuberculosis models and need now to be translated into clinical drug candidates. Such a prospect can provide an opportunity regarding the current limited therapeutic options for drug-resistant TB and the scarcity of novel antituberculosis drugs in the drug discovery pipeline.
    Language English
    Publishing date 2017-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2017.01.011
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  8. Article ; Online: Measuring efflux and permeability in mycobacteria.

    Rodrigues, Liliana / Viveiros, Miguel / Aínsa, José A

    Methods in molecular biology (Clifton, N.J.)

    2015  Volume 1285, Page(s) 227–239

    Abstract: The intrinsic resistance of mycobacteria to most antimicrobial agents is mainly attributed to the synergy between their relatively impermeable cell wall and efflux systems. The mycobacterial cell wall is rich in lipids and polysaccharides making a ... ...

    Abstract The intrinsic resistance of mycobacteria to most antimicrobial agents is mainly attributed to the synergy between their relatively impermeable cell wall and efflux systems. The mycobacterial cell wall is rich in lipids and polysaccharides making a compact envelope that limits drug uptake. Changes in cell wall composition or structure lead to variations in susceptibility to drugs. Bacterial efflux pumps are membrane proteins that are capable of actively transporting a broad range of substrates, including drugs, from the cytoplasm to the extracellular environment. Increased expression of efflux pump genes confers a low level resistance phenotype, and under these conditions, bacteria may have greater chances of acquiring chromosomal mutation(s) conferring higher levels of drug resistance. In order to develop effective antimycobacterial therapeutic strategies, the contributions to drug resistance made by the limited permeability of the cell wall and the increased expression of efflux pumps must be understood. In this chapter, we describe a method that allows: (1) the quantification of general efflux activity of mycobacterial strains (clinical isolates, mutants impaired in efflux or permeability) by the study of the transport (influx and efflux) of fluorescent compounds, such as ethidium bromide; and (2) the screening of compounds in search of inhibitors of efflux pumps, which could restore the effectiveness of antimicrobials that are subject to efflux.
    MeSH term(s) Antitubercular Agents/metabolism ; Antitubercular Agents/pharmacology ; Biological Transport ; Ethidium/metabolism ; Microbial Sensitivity Tests ; Mycobacterium/drug effects ; Mycobacterium/genetics ; Mycobacterium/metabolism ; Permeability
    Chemical Substances Antitubercular Agents ; Ethidium (EN464416SI)
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-2450-9_13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: DNA-Liposome Hybrid Carriers for Triggered Cargo Release.

    Baumann, Kevin N / Schröder, Tim / Ciryam, Prashanth S / Morzy, Diana / Tinnefeld, Philip / Knowles, Tuomas P J / Hernández-Ainsa, Silvia

    ACS applied bio materials

    2022  Volume 5, Issue 8, Page(s) 3713–3721

    Abstract: The design of simple and versatile synthetic routes to accomplish triggered-release properties in carriers is of particular interest for drug delivery purposes. In this context, the programmability and adaptability of DNA nanoarchitectures in combination ...

    Abstract The design of simple and versatile synthetic routes to accomplish triggered-release properties in carriers is of particular interest for drug delivery purposes. In this context, the programmability and adaptability of DNA nanoarchitectures in combination with liposomes have great potential to render biocompatible hybrid carriers for triggered cargo release. We present an approach to form a DNA mesh on large unilamellar liposomes incorporating a stimuli-responsive DNA building block. Upon incubation with a single-stranded DNA trigger sequence, a hairpin closes, and the DNA building block is allowed to self-contract. We demonstrate the actuation of this building block by single-molecule Förster resonance energy transfer (FRET), fluorescence recovery after photobleaching, and fluorescence quenching measurements. By triggering this process, we demonstrate the elevated release of the dye calcein from the DNA-liposome hybrid carriers. Interestingly, the incubation of the doxorubicin-laden active hybrid carrier with HEK293T cells suggests increased cytotoxicity relative to a control carrier without the triggered-release mechanism. In the future, the trigger could be provided by peritumoral nucleic acid sequences and lead to site-selective release of encapsulated chemotherapeutics.
    MeSH term(s) DNA ; Doxorubicin ; Drug Delivery Systems ; HEK293 Cells ; Humans ; Liposomes
    Chemical Substances Liposomes ; Doxorubicin (80168379AG) ; DNA (9007-49-2)
    Language English
    Publishing date 2022-07-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.2c00225
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  10. Article ; Online: DNA-Based Nanocarriers to Enhance the Optoacoustic Contrast of Tumors In Vivo.

    Joseph, James / Baumann, Kevin N / Postigo, Alejandro / Bollepalli, Laura / Bohndiek, Sarah E / Hernández-Ainsa, Silvia

    Advanced healthcare materials

    2020  Volume 10, Issue 2, Page(s) e2001739

    Abstract: Optoacoustic tomography (OT) enables non-invasive deep tissue imaging of optical contrast at high spatio-temporal resolution. The applications of OT in cancer imaging often rely on the use of molecular imaging contrast agents based on near-infrared (NIR) ...

    Abstract Optoacoustic tomography (OT) enables non-invasive deep tissue imaging of optical contrast at high spatio-temporal resolution. The applications of OT in cancer imaging often rely on the use of molecular imaging contrast agents based on near-infrared (NIR) dyes to enhance contrast at the tumor site. While these agents afford excellent biocompatibility and minimal toxicity, they present limited optoacoustic signal generation capability and rapid renal clearance, which can impede their tumor imaging efficacy. In this work, a synthetic strategy to overcome these limitations utilizing biodegradable DNA-based nanocarrier (DNA-NC) platforms is introduced. DNA-NCs enable the incorporation of NIR dyes (in this case, IRDye 800CW) at precise positions to enable fluorescence quenching and maximize optoacoustic signal generation. Furthermore, these DNA-NCs show a prolonged blood circulation compared to the native fluorophores, facilitating tumor accumulation by the enhanced permeability and retention (EPR) effect. In vivo imaging of tumor xenografts in mice following intravenous administration of DNA-NCs reveals enhanced OT signals at 24 h when compared to free fluorophores, indicating promise for this method to enhance the optoacoustic signal generation capability and tumor uptake of clinically relevant NIR dyes.
    MeSH term(s) Animals ; DNA ; Fluorescent Dyes ; Mice ; Molecular Imaging ; Neoplasms/diagnostic imaging
    Chemical Substances Fluorescent Dyes ; DNA (9007-49-2)
    Language English
    Publishing date 2020-11-16
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202001739
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