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  1. Article ; Online: Discovery of PL

    Puhl, Ana C / Godoy, Andre S / Noske, Gabriela D / Nakamura, Aline M / Gawriljuk, Victor O / Fernandes, Rafaela S / Oliva, Glaucius / Ekins, Sean

    ACS omega

    2023  Volume 8, Issue 25, Page(s) 22603–22612

    Abstract: There are very few small-molecule antivirals for SARS-CoV-2 that are either currently approved (or emergency authorized) in the US or globally, including remdesivir, molnupiravir, and paxlovid. The increasing number of SARS-CoV-2 variants that have ... ...

    Abstract There are very few small-molecule antivirals for SARS-CoV-2 that are either currently approved (or emergency authorized) in the US or globally, including remdesivir, molnupiravir, and paxlovid. The increasing number of SARS-CoV-2 variants that have appeared since the outbreak began over three years ago raises the need for continual development of updated vaccines and orally available antivirals in order to fully protect or treat the population. The viral main protease (M
    Language English
    Publishing date 2023-06-14
    Publishing country United States
    Document type Journal Article
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.3c01110
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The protein disulfide isomerase inhibitor 3-methyltoxoflavin inhibits Chikungunya virus.

    Puhl, Ana C / Fernandes, Rafaela S / Godoy, Andre S / Gil, Laura H V G / Oliva, Glaucius / Ekins, Sean

    Bioorganic & medicinal chemistry

    2023  Volume 83, Page(s) 117239

    Abstract: Chikungunya virus (CHIKV) is the etiological agent of chikungunya fever, a (re)emerging arbovirus infection, that causes severe and often persistent arthritis, as well as representing a serious health concern worldwide for which no antivirals are ... ...

    Abstract Chikungunya virus (CHIKV) is the etiological agent of chikungunya fever, a (re)emerging arbovirus infection, that causes severe and often persistent arthritis, as well as representing a serious health concern worldwide for which no antivirals are currently available. Despite efforts over the last decade to identify and optimize new inhibitors or to reposition existing drugs, no compound has progressed to clinical trials for CHIKV and current prophylaxis is based on vector control, which has shown limited success in containing the virus. Our efforts to rectify this situation were initiated by screening 36 compounds using a replicon system and ultimately identified the natural product derivative 3-methyltoxoflavin with activity against CHIKV using a cell-based assay (EC
    MeSH term(s) Animals ; Humans ; Mice ; Antiviral Agents/chemistry ; Caco-2 Cells ; Chikungunya Fever/drug therapy ; Chikungunya virus/physiology ; Protein Disulfide-Isomerases/antagonists & inhibitors ; Virus Replication/drug effects ; Flavins/chemistry ; Flavins/pharmacology
    Chemical Substances Antiviral Agents ; Protein Disulfide-Isomerases (EC 5.3.4.1) ; Flavins
    Language English
    Publishing date 2023-03-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2023.117239
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Development of a Halochromic, Antimicrobial, and Antioxidant Starch-Based Film Containing Phenolic Extract from Jaboticaba Peel.

    Luz, Rafaela F / Ferreira, Richard D R / Silva, Cassio N S / Miranda, Bruna M / Piccoli, Roberta H / Silva, Monique S / Paula, Ladyslene C / Leles, Maria Inês G / Fernandes, Kátia F / Cruz, Maurício V / Batista, Karla A

    Foods (Basel, Switzerland)

    2023  Volume 12, Issue 3

    Abstract: In this study, the antioxidant, antimicrobial, mechanical, optical, and barrier attributes ... ...

    Abstract In this study, the antioxidant, antimicrobial, mechanical, optical, and barrier attributes of
    Language English
    Publishing date 2023-02-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704223-6
    ISSN 2304-8158
    ISSN 2304-8158
    DOI 10.3390/foods12030653
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Assessing the Genotoxicity of Cellulose Nanomaterials in a Co-Culture of Human Lung Epithelial Cells and Monocyte-Derived Macrophages.

    Ventura, Célia / Pinto, Fátima / Lourenço, Ana Filipa / Pedrosa, Jorge F S / Fernandes, Susete N / da Rosa, Rafaela R / Godinho, Maria Helena / Ferreira, Paulo J T / Louro, Henriqueta / Silva, Maria João

    Bioengineering (Basel, Switzerland)

    2023  Volume 10, Issue 8

    Abstract: Cellulose micro/nanomaterials (CMNMs) are innovative materials with a wide spectrum of industrial and biomedical applications. Although cellulose has been recognized as a safe material, the unique properties of its nanosized forms have raised concerns ... ...

    Abstract Cellulose micro/nanomaterials (CMNMs) are innovative materials with a wide spectrum of industrial and biomedical applications. Although cellulose has been recognized as a safe material, the unique properties of its nanosized forms have raised concerns about their safety for human health. Genotoxicity is an endpoint that must be assessed to ensure that no carcinogenic risks are associated with exposure to nanomaterials. In this study, we evaluated the genotoxicity of two types of cellulose micro/nanofibrils (CMF and CNF) and one sample of cellulose nanocrystals (CNC), obtained from industrial bleached
    Language English
    Publishing date 2023-08-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2746191-9
    ISSN 2306-5354
    ISSN 2306-5354
    DOI 10.3390/bioengineering10080986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A Modified ELISA Method to Evaluate the Interaction of Schistosoma mansoni Proteins with Plasminogen.

    Fernandes, Luis G V / Fernandes, Rafaela S / Nascimento, Ana L T O / Leite, Luciana C C

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

    2020  Volume 2151, Page(s) 185–195

    Abstract: ... Kringle domains. To assess the activation of S. mansoni recombinant protein-bound PLG, the amidolytic activity ...

    Abstract An important aspect of host-pathogen interactions is the interference of secreted proteins with the fibrinolytic system. Herein, we describe a modified ELISA method used to evaluate the interaction of a recombinant Schistosoma mansoni protein with plasminogen (PLG). Using this protocol, we demonstrated that a secreted protein, recombinant venom allergen-like protein 18 (rSmVAL18) acts as a plasminogen receptor increasing its activation into plasmin in the presence of the urokinase-type plasminogen activator (uPA). PLG binding was determined by immobilizing human PLG in the plate and incubating with the recombinant protein; competitive binding with a lysine analog demonstrated the interaction of the protein lysine residues with PLG Kringle domains. To assess the activation of S. mansoni recombinant protein-bound PLG, the amidolytic activity of generated plasmin was measured using the D-Val-Leu-Lys 4-nitroanilide dihydrochloride substrate.
    MeSH term(s) Aminocaproic Acid/metabolism ; Animals ; Binding, Competitive ; Enzyme-Linked Immunosorbent Assay/methods ; Fibrinolysin/metabolism ; Helminth Proteins/metabolism ; Humans ; Plasminogen/metabolism ; Protein Binding ; Schistosoma mansoni/metabolism
    Chemical Substances Helminth Proteins ; Plasminogen (9001-91-6) ; Fibrinolysin (EC 3.4.21.7) ; Aminocaproic Acid (U6F3787206)
    Language English
    Publishing date 2020-05-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0635-3_15
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Therapeutic applications of snake venoms: An invaluable potential of new drug candidates.

    Diniz-Sousa, Rafaela / Caldeira, Cleópatra A da S / Pereira, Soraya S / Da Silva, Saulo L / Fernandes, Pedro A / Teixeira, Luís M C / Zuliani, Juliana P / Soares, Andreimar M

    International journal of biological macromolecules

    2023  Volume 238, Page(s) 124357

    Abstract: Animal venoms and their chemical compounds have aroused both empirical and scientific attention for ages. However, there has been a significant increase in scientific investigations in recent decades, allowing the production of various formulations that ... ...

    Abstract Animal venoms and their chemical compounds have aroused both empirical and scientific attention for ages. However, there has been a significant increase in scientific investigations in recent decades, allowing the production of various formulations that are helping in the development of many important tools for biotechnological, diagnostic, or therapeutic use, both in human and animal health, as well as in plants. Venoms are composed of biomolecules and inorganic compounds that may have physiological and pharmacological activities that are not related to their principal actions (prey immobilization, digestion, and defense). Snake venom toxins, mainly enzymatic and non-enzymatic proteins, and peptides have been identified as potential prototypes for new drugs and/or models for the development of pharmacologically active structural domains for the treatment of cancer, cardiovascular diseases, neurodegenerative and autoimmune diseases, pain, and infectious-parasitic diseases. This minireview aims to provide an overview of the biotechnological potential of animal venoms, with a focus on snakes, and to introduce the reader to the fascinating world of Applied Toxinology, where animal biodiversity can be used to develop therapeutic and diagnostic applications for humans.
    MeSH term(s) Animals ; Humans ; Snake Venoms/chemistry ; Snakes/metabolism ; Proteins/chemistry ; Peptides/pharmacology ; Neoplasms/drug therapy
    Chemical Substances Snake Venoms ; Proteins ; Peptides
    Language English
    Publishing date 2023-04-05
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 282732-3
    ISSN 1879-0003 ; 0141-8130
    ISSN (online) 1879-0003
    ISSN 0141-8130
    DOI 10.1016/j.ijbiomac.2023.124357
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Analysis of selective fluorescence for the characterization of microplastic fibers: Use of a Nile Red-based analytical method to compare between natural and synthetic fibers.

    Galvão, Luciana S / Ferreira, Rafaela R / Fernandes, Emília M S / Correia, Carla Almêda / Valera, Ticiane S / Dos Santos Rosa, Derval / Wiebeck, Hélio

    Journal of hazardous materials

    2022  Volume 443, Issue Pt A, Page(s) 130217

    Abstract: The scientific community has been focusing on studying and understanding the extent of damage caused by microplastics (MPs) to flora, fauna, and humans, including the environmental and health risks associated with them. MPs with different morphologies ... ...

    Abstract The scientific community has been focusing on studying and understanding the extent of damage caused by microplastics (MPs) to flora, fauna, and humans, including the environmental and health risks associated with them. MPs with different morphologies have been described in different environments, with fibers being the most common type regardless of the environment. Various methods have been used to analyze MPs. Analytical methodologies such as visual inspection, spectroscopic methods, and others currently used to study MPs are time-consuming, and only subjective results are obtained when these methods are used for sample analysis. Researchers have used various dyes, such as Nile Red (NR), a selective fluorescent stain, to differentiate the polymers from the other sample components and address these problems. Using such dyes helps distinguish polymer particles from other contaminants present in the samples. We aimed to study the analytical process, morphology, and wettability of synthetic (such as polyethylene and polypropylene) and natural (such as linen and cotton) fibers using NR to characterize the fibers. The fibers were fragmented manually, and the samples were prepared using a cryomicrotome. The prepared samples were subjected to different NR incubation times of 30 min, 24 h, and 168 h, and characterized under ultraviolet light using optical microscopy. We investigated the effect of NR on different fibers, and the samples selection using the fluorescence properties generated when the fibers adsorbed the NR dye. The wettabilities of the samples indicated that polyethylene and polypropylene were hydrophobic, while linen and cotton were hydrophilic. Both synthetic and natural fibers exhibited fluorescence properties in the presence of NR. This increased the complexity of executing the MP characterization process, indicating that combined methodologies and optical and chemical identification processes should be used to characterize plastic specimens efficiently. We summarize and discuss the results and findings and provide recommendations for future laboratory research on microplastic fibers focusing on (I) microplastic selection, (II) stain preparation, and (III) microplastic characterization.
    MeSH term(s) Humans ; Microplastics ; Plastics/chemistry ; Polypropylenes ; Fluorescence ; Environmental Monitoring/methods ; Water Pollutants, Chemical/chemistry ; Polyethylene/analysis ; Coloring Agents
    Chemical Substances Microplastics ; Plastics ; nile red (P476F1L81G) ; Polypropylenes ; Water Pollutants, Chemical ; Polyethylene (9002-88-4) ; Coloring Agents
    Language English
    Publishing date 2022-10-20
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1491302-1
    ISSN 1873-3336 ; 0304-3894
    ISSN (online) 1873-3336
    ISSN 0304-3894
    DOI 10.1016/j.jhazmat.2022.130217
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Therapeutic applications of snake venoms: An invaluable potential of new drug candidates

    Diniz-Sousa, Rafaela / Caldeira, Cleópatra A. da S. / Pereira, Soraya S. / Da Silva, Saulo L. / Fernandes, Pedro A. / Teixeira, Luís M.C. / Zuliani, Juliana P. / Soares, Andreimar M.

    International Journal of Biological Macromolecules. 2023 May, v. 238 p.124357-

    2023  

    Abstract: Animal venoms and their chemical compounds have aroused both empirical and scientific attention for ages. However, there has been a significant increase in scientific investigations in recent decades, allowing the production of various formulations that ... ...

    Abstract Animal venoms and their chemical compounds have aroused both empirical and scientific attention for ages. However, there has been a significant increase in scientific investigations in recent decades, allowing the production of various formulations that are helping in the development of many important tools for biotechnological, diagnostic, or therapeutic use, both in human and animal health, as well as in plants. Venoms are composed of biomolecules and inorganic compounds that may have physiological and pharmacological activities that are not related to their principal actions (prey immobilization, digestion, and defense). Snake venom toxins, mainly enzymatic and non-enzymatic proteins, and peptides have been identified as potential prototypes for new drugs and/or models for the development of pharmacologically active structural domains for the treatment of cancer, cardiovascular diseases, neurodegenerative and autoimmune diseases, pain, and infectious-parasitic diseases. This minireview aims to provide an overview of the biotechnological potential of animal venoms, with a focus on snakes, and to introduce the reader to the fascinating world of Applied Toxinology, where animal biodiversity can be used to develop therapeutic and diagnostic applications for humans.
    Keywords biodiversity ; digestion ; drugs ; medicinal properties ; pain ; peptides ; snake venoms ; snakes ; therapeutics ; Therapeutic applications ; Venom ; Snake ; Toxins
    Language English
    Dates of publication 2023-05
    Publishing place Elsevier B.V.
    Document type Article ; Online
    ZDB-ID 282732-3
    ISSN 1879-0003 ; 0141-8130
    ISSN (online) 1879-0003
    ISSN 0141-8130
    DOI 10.1016/j.ijbiomac.2023.124357
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication.

    Fernandes, Rafaela S / Noske, Gabriela D / Gawriljuk, Victor O / de Oliveira, Ketllyn I Z / Godoy, Andre S / Mesquita, Nathalya C M R / Oliva, Glaucius

    Journal of visualized experiments : JoVE

    2021  , Issue 176

    Abstract: Antiviral drug discovery requires the development of reliable biochemical and cellular assays that can be performed in high-throughput screening (HTS) formats. The flavivirus non-structural (NS) proteins are thought to co-translationally assemble on the ... ...

    Abstract Antiviral drug discovery requires the development of reliable biochemical and cellular assays that can be performed in high-throughput screening (HTS) formats. The flavivirus non-structural (NS) proteins are thought to co-translationally assemble on the endoplasmic reticulum (ER) membranes, forming the replication complex (RC). The NS3 and NS5 are the most studied enzymes of the RC and constitute the main targets for drug development due to their crucial roles in viral genome replication. NS3 protease domain, which requires NS2B as its cofactor, is responsible for the cleavage of the immature viral polyprotein into the mature NS proteins, whereas NS5 RdRp domain is responsible for the RNA replication. Herein, we describe in detail the protocols used in replicon-based screenings and enzymatic assays to test large compound libraries for inhibitors of the Zika virus (ZIKV) replication. Replicons are self-replicating subgenomic systems expressed in mammalian cells, in which the viral structural genes are replaced by a reporter gene. The inhibitory effects of compounds on viral RNA replication can be easily evaluated by measuring the reduction in the reporter protein activity. The replicon-based screenings were performed using a BHK-21 ZIKV replicon cell line expressing Renilla luciferase as a reporter gene. To characterize the specific targets of identified compounds, we established in-vitro fluorescence-based assays for recombinantly expressed NS3 protease and NS5 RdRp. The proteolytic activity of the viral protease was measured by using the fluorogenic peptide substrate Bz-nKRR-AMC, while the NS5 RdRp elongation activity was directly detected by the increase of the fluorescent signal of SYBR Green I during RNA elongation, using the synthetic biotinylated self-priming template 3'UTR-U30 (5'-biotin-U30-ACUGGAGAUCGAUCUCCAGU-3').
    MeSH term(s) Animals ; Antiviral Agents/metabolism ; High-Throughput Screening Assays ; Mammals ; Virus Replication ; Zika Virus/genetics ; Zika Virus Infection/drug therapy
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2021-10-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/62422
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Combinatorial delivery of doxorubicin and acridine orange by gold core silica shell nanospheres functionalized with poly(ethylene glycol) and 4-methoxybenzamide for cancer targeted therapy.

    Guimarães, Rafaela S / Rodrigues, Carolina F / Fernandes, Natanael / de Melo-Diogo, Duarte / Ferreira, Paula / Correia, Ilídio J / Moreira, André F

    Journal of inorganic biochemistry

    2021  Volume 219, Page(s) 111433

    Abstract: Combinatorial therapies based on the simultaneous administration of multiple drugs can lead to synergistic effects, increasing the efficacy of the cancer therapy. However, it is crucial to develop new delivery systems that can increase the drugs' ... ...

    Abstract Combinatorial therapies based on the simultaneous administration of multiple drugs can lead to synergistic effects, increasing the efficacy of the cancer therapy. However, it is crucial to develop new delivery systems that can increase the drugs' therapeutic selectivity and efficacy. Gold core silica shell (AuMSS) nanoparticles present physicochemical properties that allow their simultaneous application as drug delivery and imaging agents. Herein, poly(ethylene glycol) was modified with 4-methoxybenzamide and 3-(triethoxysilyl)propyl isocyanate (TPANIS) to create a novel surface functionalization capable of improving the colloidal stability and specificity of AuMSS nanospheres towards cancer cells. Moreover, a dual drug combination based on Doxorubicin (DOX) and Acridine orange (AO) was characterized and administered using the AuMSS-TPANIS nanospheres. The obtained results show that the DOX:AO drug combination can mediate a synergistic therapeutic effect in both HeLa and MCF-7 cells, particularly at the 2:1, 1:1, and 1:2 ratios. Additionally, the TPANIS functionalization increased the AuMSS nanospheres colloidal stability and selectivity towards MCF-7 cancer cells (overexpressing sigma receptors). Such also resulted in an enhanced cytotoxic effect against MCF-7 cells when administering the DOX:AO drug combination with the AuMSS-TPANIS nanospheres. Overall, the obtained results confirm the therapeutic potential of the DOX:AO drug combination as well as the targeting capacity of AuMSS-TPANIS, supporting its application in the cancer-targeted combinatorial chemotherapy.
    MeSH term(s) Acridine Orange/chemistry ; Acridine Orange/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/chemistry ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Benzamides/chemistry ; Cell Survival/drug effects ; Doxorubicin/chemistry ; Doxorubicin/pharmacology ; Drug Delivery Systems/methods ; Gold/chemistry ; HeLa Cells ; Humans ; MCF-7 Cells ; Nanospheres/chemistry ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Polyethylene Glycols/chemistry ; Silicon Dioxide/chemistry
    Chemical Substances Benzamides ; Polyethylene Glycols (3WJQ0SDW1A) ; Gold (7440-57-5) ; Silicon Dioxide (7631-86-9) ; Doxorubicin (80168379AG) ; Acridine Orange (F30N4O6XVV)
    Language English
    Publishing date 2021-03-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 162843-4
    ISSN 1873-3344 ; 0162-0134
    ISSN (online) 1873-3344
    ISSN 0162-0134
    DOI 10.1016/j.jinorgbio.2021.111433
    Database MEDical Literature Analysis and Retrieval System OnLINE

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