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4. Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID‐19): autopsy reveals a ferroptosis signature

Author

Werner Jacobs, Martin Lammens, Annelies Kerckhofs, Evy Voets, Emily Van San, Samya Van Coillie, Cédric Peleman, Matthias Mergeay, Sabriya Sirimsi, Veerle Matheeussen, Hilde Jansens, Ingrid Baar, Tom Vanden Berghe, and Philippe G. Jorens

Subjects
Lymphocytic myocarditis, SARS‐CoV‐2‐infection, COVID‐19, Autopsy, Renal failure, Ferroptosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims Cardiovascular complications, including myocarditis, are observed in coronavirus disease 2019 (COVID‐19). Major cardiac involvement is a potentially lethal feature in severe cases. We sought to describe the underlying pathophysiological mechanism in COVID‐19 lethal cardiogenic shock. Methods and results We report on a 48‐year‐old male COVID‐19 patient with cardiogenic shock; despite extracorporeal life support, dialysis, and massive pharmacological support, this rescue therapy was not successful. Severe acute respiratory syndrome coronavirus 2 RNA was detected at autopsy in the lungs and myocardium. Histopathological examination revealed diffuse alveolar damage, proliferation of type II pneumocytes, lymphocytes in the lung interstitium, and pulmonary microemboli. Moreover, patchy muscular, sometimes perivascular, interstitial mononuclear inflammatory infiltrates, dominated by lymphocytes, were seen in the cardiac tissue. The lymphocytes ‘interlocked’ the myocytes, resulting in myocyte degeneration and necrosis. Predominantly, T‐cell lymphocytes with a CD4:CD8 ratio of 1.7 infiltrated the interstitial myocardium, reflecting true myocarditis. The myocardial tissue was examined for markers of ferroptosis, an iron‐catalysed form of regulated cell death that occurs through excessive peroxidation of polyunsaturated fatty acids. Immunohistochemical staining with E06, a monoclonal antibody binding to oxidized phosphatidylcholine (reflecting lipid peroxidation during ferroptosis), was positive in morphologically degenerating and necrotic cardiomyocytes adjacent to the infiltrate of lymphocytes, near arteries, in the epicardium and myocardium. A similar ferroptosis signature was present in the myocardium of a COVID‐19 subject without myocarditis. In a case of sudden death due to viral myocarditis of unknown aetiology, however, immunohistochemical staining with E06 was negative. The renal proximal tubuli stained positively for E06 and also hydroxynonenal (4‐HNE), a reactive breakdown product of the lipid peroxides that execute ferroptosis. In the case of myocarditis of other aetiology, the renal tissue displayed no positivity for E06 or 4‐HNE. Conclusions The findings in this case are unique as this is the first report on accumulated oxidized phospholipids (or their breakdown products) in myocardial and renal tissue in COVID‐19. This highlights ferroptosis, proposed to detrimentally contribute to some forms of ischaemia–reperfusion injury, as a detrimental factor in COVID‐19 cardiac damage and multiple organ failure.

Published
2020
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5. Comparison of a VLP‐based and GST‐L1‐based multiplex immunoassay to detect vaccine‐induced HPV‐specific antibodies in first‐void urine

Author

Laura Téblick, Elizabeth R. Unger, Tim Waterboer, Alex Vorsters, Pierre Van Damme, Martina Willhauck-Fleckenstein, Gitika Panicker, Veerle Matheeussen, Severien Van Keer, Wiebren A.A. Tjalma, Jade Pattyn, Zoë Pieters, Pattyn, Jade, Panicker, Gitika, Willhauck-Fleckenstein, Martina, Van Keer, Severien, Teblick, Laura, PIETERS, Zoe, Tjalma, Wiebren A. A., Matheeussen, Veerle, Van Damme, Pierre, Waterboer, Tim, Unger, Elizabeth R., and Vorsters, Alex

Subjects
Urine, HPV vaccines, HPV serology, 03 medical and health sciences, 0302 clinical medicine, First void urine, Virology, Medicine, Multiplex, 030212 general & internal medicine, Human papillomavirus, HPV antibodies, human papillomavirus, Research Articles, biology, medicine.diagnostic_test, business.industry, urine, Specific antibody, Infectious Diseases, Immunoassay, biology.protein, 030211 gastroenterology & hepatology, Human medicine, Antibody, business, Research Article
Abstract

Vaccine‐induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first‐void (FV) urine. This presents a novel opportunity for noninvasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared the measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus‐like particles (VLP)‐based ELISA (M4ELISA) with previously reported results using a glutathione S‐transferase (GST)‐L1‐based immunoassay (GST‐L1‐MIA). We tested 53 paired FV urine and serum samples from 19‐ to 26‐year‐old healthy women, unvaccinated (n = 17) or vaccinated with either the bivalent or quadrivalent HPV‐vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST‐L1‐MIA results. Inter‐assay and inter‐specimen correlations were examined using the Spearman's rank test (rs). As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine P = .0003; serum P ≤ .0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti‐HPV6/11/16/18, r s = 0.85/0.86/0.91/0.79, P ≤ .001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST‐L1‐MIA (FV urine anti‐HPV6/11/16/18, r s = 0.86/0.83/0.89/0.53, P ≤ .0001; serum anti‐HPV6/11/16/18, r s = 0.93/0.89/0.94/0.75, P ≤ .0001). FV urine HPV antibody detection is comparable with both assays, further supporting this noninvasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine‐induced HPV antibody detection., Highlights First‐void urine HPV antibody detection is comparable with both assays.Urine of vaccinees contain higher antibody levels as opposed to unvaccinated women.Urinary HPV6/11/16/18 antibodies correlate significantly with paired sera.Urine might offer a non‐invasive tool to assess serum antibody transudate.Approaches to improve the sensitivity of vaccine‐induced HPV antibody detection in FV urine are required.

Published
2020
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6. Semisynthetic triterpenes led to the generation of selective antitrypanosomal lead compounds

Author

Guilhon‐Simplicio, Fernanda, primary, Serrão, Carlos Klinger Rodrigues, additional, Pinto, Ana Cristina da Silva, additional, Pacheco, Paulo Anastácio Furtado, additional, Faria, Robson Xavier, additional, Rocha, David Rodrigues, additional, Ferreira, Vitor Francisco, additional, Pereira‐Junior, Raimundo Carlos, additional, Matheeussen, An, additional, Baán, Adrienn, additional, Kiekens, Filip, additional, Meneses Pereira, Maria, additional, Lima, Emerson Silva, additional, Winter, Hans De, additional, and Cos, Paul, additional

Published
2022
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8. Front Cover: Synthesis and Structure−Activity Relationships of Imidazopyridine/Pyrimidine‐ and Furopyridine‐Based Anti‐infective Agents against Trypanosomiases (6/2021)

Author

G. Silva, Daniel, primary, Junker, Anna, additional, M. G. de Melo, Shaiani, additional, Fumagalli, Fernando, additional, Robert Gillespie, J., additional, Molasky, Nora, additional, S. Buckner, Frederick, additional, Matheeussen, An, additional, Caljon, Guy, additional, Maes, Louis, additional, and S. Emery, Flavio, additional

Published
2021
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9. Synthesis and Structure−Activity Relationships of Imidazopyridine/Pyrimidine‐ and Furopyridine‐Based Anti‐infective Agents against Trypanosomiases

Author

Silva, Daniel G., primary, Junker, Anna, additional, Melo, Shaiani M. G., additional, Fumagalli, Fernando, additional, Gillespie, J. Robert, additional, Molasky, Nora, additional, Buckner, Frederick S., additional, Matheeussen, An, additional, Caljon, Guy, additional, Maes, Louis, additional, and Emery, Flavio S., additional

Published
2020
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10. A split strategy to prevent cytomegalovirus after kidney transplantation using prophylaxis in serological high‐risk patients and a pre‐emptive strategy in intermediate‐risk patients: Combining the best of two options?

Author

Hellemans, Rachel, primary, Wijtvliet, Veerle, additional, Bergs, Kristof, additional, Philipse, Ester, additional, Vleut, Rowena, additional, Massart, Annick, additional, Couttenye, Marie‐Madeleine, additional, Matheeussen, Veerle, additional, and Abramowicz, Daniel, additional

Published
2020
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11. Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID‐19): autopsy reveals a ferroptosis signature

Author

Jacobs, Werner, primary, Lammens, Martin, additional, Kerckhofs, Annelies, additional, Voets, Evy, additional, Van San, Emily, additional, Van Coillie, Samya, additional, Peleman, Cédric, additional, Mergeay, Matthias, additional, Sirimsi, Sabriya, additional, Matheeussen, Veerle, additional, Jansens, Hilde, additional, Baar, Ingrid, additional, Vanden Berghe, Tom, additional, and Jorens, Philippe G., additional

Published
2020
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12. Comparison of a VLP‐based and GST‐L1‐based multiplex immunoassay to detect vaccine‐induced HPV‐specific antibodies in first‐void urine

Author

Pattyn, Jade, primary, Panicker, Gitika, additional, Willhauck‐Fleckenstein, Martina, additional, Van Keer, Severien, additional, Téblick, Laura, additional, Pieters, Zoë, additional, Tjalma, Wiebren A. A., additional, Matheeussen, Veerle, additional, Van Damme, Pierre, additional, Waterboer, Tim, additional, Unger, Elizabeth R., additional, and Vorsters, Alex, additional

Published
2020
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13. Front Cover: Synthesis and Structure−Activity Relationships of Imidazopyridine/Pyrimidine‐ and Furopyridine‐Based Anti‐infective Agents against Trypanosomiases (6/2021)

Author

Frederick S. Buckner, Guy Caljon, Fernando Fumagalli, An Matheeussen, Daniel G. Silva, Shaiani Maria Gil de Melo, Anna Junker, Louis Maes, J. Robert Gillespie, Flavio da Silva Emery, and Nora Molasky

Subjects
Pharmacology, Imidazopyridine, Pyrimidine, Organic Chemistry, Biochemistry, Combinatorial chemistry, chemistry.chemical_compound, Front cover, chemistry, Drug Discovery, Molecular Medicine, Anti infectives, General Pharmacology, Toxicology and Pharmaceutics, Anti-Infective Agents
Published
2021
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16. Structure elucidation and NMR assignments of two new triterpenoids from the stems of Paragonia pyramidata (Bignoniaceae)

Author

Anne-Emmanuelle Hay, Xiao-Ling Wang, Kurt Hostettmann, An Matheeussen, and Mahabir P. Gupta

Subjects
Stigmasterol, biology, Chemistry, Stereochemistry, Bignoniaceae, General Chemistry, Carbon-13 NMR, biology.organism_classification, chemistry.chemical_compound, Proton NMR, Organic chemistry, General Materials Science, Oleanolic acid, Two-dimensional nuclear magnetic resonance spectroscopy, Heteronuclear single quantum coherence spectroscopy, Lupeol
Abstract

Phytochemical investigation of dichloromethane (DCM) extract from the stems of Paragonia pyramidata var. pyramidata L. Rich. (Bur.) resulted in the isolation and characterization of two new triterpenoids 3β,19β-dihydroxylup-12, 20(29)-diene-28-oic acid (1) and 3β,19β-dihydroxylup-12-en-28-oic acid (2), three known triterpenoids lupeol (3), spinosic acid A (4) and oleanolic acid (5), together with four known steroids (20R)-22E-24-ethylcholesta-4,22-dien-3-one (6), (20R)-24-ethylcholest-4-en-3-one (7), stigmasterol (8) and β-sitosterol (9). HREIMS, GC-MS and NMR experiments including HSQC, HMBC, COSY and NOESY were used for the determination of the structures and NMR spectral assignments. This is the first report about the chemical constituents for this plant.

Published
2011
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17. Antimicrobial Evaluation of the Polyisoprenylated Benzophenones Nemorosone and Guttiferone A

Author

L. Maes, Paul Cos, Osmany Cuesta-Rubio, Lianet Monzote, T. Van Assche, and A. Matheeussen

Subjects
Pharmacology, 010405 organic chemistry, medicine.drug_class, Clusiaceae, Trichophyton rubrum, Biology, Pharmacognosy, 010402 general chemistry, biology.organism_classification, Antimicrobial, 01 natural sciences, Terpenoid, 3. Good health, 0104 chemical sciences, Microbiology, Antiprotozoal, medicine, Candida albicans, Antibacterial agent
Abstract

Polyisoprenylated benzophenones have been isolated from plants, particularly in the Clusiaceae family, and their biological properties recently have received considerable attention from a pharmacological point of view. The aim of the study was to investigate the polyisoprenylated benzophenones, nemorosone and guttiferone A, for their antimicrobial effect against a panel of bacteria, fungi and protozoan parasites. They showed a moderate activity against the Gram-positive bacterium Staphylococcus aureus, while no activity was demonstrated against Escherichia coli and the fungi Trichophyton rubrum and Candida albicans. An interesting activity was found for Plasmodium falciparum with IC50 values lower than 1 μm, while cytotoxicity on MRC-5 cells revealed CC50 values of 15.5 and 12.0 μm, respectively, for nemorosone and guttiferone A. Copyright © 2011 John Wiley & Sons, Ltd.

Published
2011
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18. Antimalarial activity of extract and norbergenin derivatives from the stem bark of Diospyros sanza-minika A. Chevalier (Ebenaceae)

Author

Kurt Hostettmann, Jean Gustave Tangmouo, An Matheeussen, Raimana Ho, Alain Meli Lannang, Louis Maes, Justin Komguem, and Bernadette Biloa Messi

Subjects
Diospyros sanza-minika, Plasmodium falciparum, Pharmacognosy, Cell Line, Norbergenin, Antimalarials, chemistry.chemical_compound, Humans, Benzopyrans, Medicinal plants, Pharmacology, Stem bark, Molecular Structure, Traditional medicine, biology, Plant Extracts, Pharmacology. Therapy, Diospyros, biology.organism_classification, Chemistry, chemistry, visual_art, Plant Bark, visual_art.visual_art_medium, Bark, Ebenaceae
Abstract

The methanol extract from the stem bark of Diospyros sanza-minika as well as five norbergenin derivatives isolated from this crude extract were evaluated for their in vitro activity against Plasmodium falciparum K1 and cytotoxicity on MRC-5 cells. 4-O-(3'-methylgalloyl)norbergenin was found to be the most potent compound (IC(50) 0.6 μg/mL; CC(50) 24.7 μg/mL), followed by 4-O-galloylnorbergenin (IC(50) 3.9 μg/mL; CC(50) > 64 μg/mL) and 11-O-p-hydroxy-benzoyl-norbergenin (IC(50) 4.9 μg/mL; CC(50) > 64 μg/mL). Norbergenin and 4-O-syringoylnorbergenin were inactive (IC(50) > 32 μg/mL; CC(50) > 64 μg/mL). The antimalarial activity of the pure constituents and of the methanol extract from the stem bark of Diospyros sanza-minika is reported for the first time. The results provide interesting baseline information for the potential use of the crude extract well as some of the isolated compounds in the search for novel antimalarial compounds.

Published
2010
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20. Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing‐induced heart failure

Author

Gomez, Nelson, primary, Touihri, Karim, additional, Matheeussen, Veerle, additional, Da Costa, Agnès Mendes, additional, Mahmoudabady, Maryam, additional, Mathieu, Myrielle, additional, Baerts, Lesley, additional, Peace, Aaron, additional, Lybaert, Pascale, additional, Scharpé, Simon, additional, De Meester, Ingrid, additional, Bartunek, Jozef, additional, Vanderheyden, Marc, additional, and McEntee, Kathleen, additional

Published
2012
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24. Synthesis and Antiplasmodial Activity of Highly Active Reverse Analogues of the Antimalarial Drug Candidate Fosmidomycin

Author

Behrendt, Christoph T., primary, Kunfermann, Andrea, additional, Illarionova, Victoria, additional, Matheeussen, An, additional, Gräwert, Tobias, additional, Groll, Michael, additional, Rohdich, Felix, additional, Bacher, Adelbert, additional, Eisenreich, Wolfgang, additional, Fischer, Markus, additional, Maes, Louis, additional, and Kurz, Thomas, additional

Published
2010
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