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Virmani I., Oteo A., Dunn M., Vidler D., Roper C., Officer J., Hardy G., Dargan P. I., Eddleston M., Cooper J. G., Hill S. L., Macfarlane R., Keating L., Haden M., Hudson S., Thomas S. H. L.* (2022): Accuracy of substance exposure history in patients attending emergency departments after substance misuse; a comparison with biological sample analysis. Clinical Toxicology 1–9 (in press).
tandfonline.com/doi/full/10.10

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Takahashi H., Sovadinova I., Yasuhara K., Vemparala S., Caputo G. A.*, Kuroda, K.* (2022): Biomimetic antimicrobial polymers—Design, characterization, antimicrobial, and novel applications. WIREs Nanomedicine and Nanobiotechnology (in press).
wires.onlinelibrary.wiley.com/

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Bajard L., Adamovsky O., Audouze K. , Baken K., Barouki R., Beltman J. B., Beronius A., Bonefeld-Jørgensen E. C., Cano-Sancho G., de Baat M. L., Di Tillio F., Fernández M. F., FitzGerald R. E., Gundacker C., Hernández A. F., Hilscherova K., Karakitsios S., Kuchovska E., Long M., Luijten M., Majid S., Marx-Stoelting P., Mustieles V., Negi C. K., Sarigiannis D., Scholtz S., Sovadinova I., Stierum R., Tanabe S., Tollefsen K. E., van den Brand A. D., Vogs C., Wielsøe M., Wittwehr C., Blaha L.* (2022): Application of AOPs to assist regulatory assessment of chemical risks – Case studies, needs and recommendation. Environmental Research (in press).
sciencedirect.com/science/arti

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Sehnal L., Smutná M., Bláhová L., Babica P., Šplíchalová P., Hilscherová K.* (2022): The origin of teratogenic retinoids in cyanobacteria. Toxins 14(9), 636.
mdpi.com/2072-6651/14/9/636

The Origin of Teratogenic Retinoids in Cyanobacteria

Although information about the occurrence and distribution of retinoids in the environment is scarce, cyanobacterial water blooms have been identified as a significant source of these small molecules. Despite the confirmed presence of retinoids in the freshwater blooms dominated by cyanobacteria and their described teratogenic effects, reliable identification of retinoid producers and the mechanism of their biosynthesis is missing. In this study, the cultures of several taxonomically diverse species of axenic cyanobacteria were confirmed as significant producers of retinoid-like compounds. The consequent bioinformatic analysis suggested that the enzymatic background required for the biosynthesis of all-trans retinoic acid from retinal is not present across phylum Cyanobacteria. However, we demonstrated that retinal conversion into other retinoids can be mediated non-enzymatically by free radical oxidation, which leads to the production of retinoids widely detected in cyanobacteria and environmental water blooms, such as all-trans retinoic acid or all-trans 5,6epoxy retinoic acid. Importantly, the production of these metabolites by cyanobacteria in association with the mass development of water blooms can lead to adverse impacts in aquatic ecosystems regarding the described teratogenicity of retinoids. Moreover, our finding that retinal can be non-enzymatically converted into more bioactive retinoids, also in water, and out of the cells, increases the environmental significance of this process.

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Bernal K., Charbel T., Erradhouani C., Boronat-Belda T., Gaillard L., Kassir S., Le Mentec H., Martin-Chouly C., Podechard N., Lagadic-Gossmann D., Langouet S., Brion F., Knoll-Gellida A., Babin P. J., Sovadinova I., Babica P., Andreau K., Barouki R., Vondracek J., Alonso-Magdalena P., Blanc E., Kim M.-J.*, Coumoul X.* (2022): Combinatorial pathway disruption as an approach to delineate metabolic impacts of endocrine disruptors. FEBS Letters (online ahead of print)
febs.onlinelibrary.wiley.com/d

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Sychrová E., Smutná M., Nováková K., Hilscherová K.* (2022): Potential estrogenic background in aquatic laboratory cultivations. Aquatic Toxicology 247:106169.
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Sychrová E., Yawer A., Labohá P., Basu A., Dydowiczová A., Virmani I., Babica P., Sovadinová I.* (2022): Testicular toxicity of environmentally relevant endocrine-disrupting chemicals in 2D and 3D in vitro models of Leydig cells. Environmental Toxicology and Pharmacology 93:103869.
sciencedirect.com/science/arti

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Durník R., Šindlerová L., Babica P., Jurček O.* (2022): Bile acids transporters of enterohepatic circulation for targeted drug delivery. Molecules 27(9):2961.
mdpi.com/1420-3049/27/9/2961

Bile Acids Transporters of Enterohepatic Circulation for Targeted Drug Delivery

Bile acids (BAs) are important steroidal molecules with a rapidly growing span of applications across a variety of fields such as supramolecular chemistry, pharmacy, and biomedicine. This work provides a systematic review on their transport processes within the enterohepatic circulation and related processes. The focus is laid on the description of specific or less-specific BA transport proteins and their localization. Initially, the reader is provided with essential information about BAs′ properties, their systemic flow, metabolism, and functions. Later, the transport processes are described in detail and schematically illustrated, moving step by step from the liver via bile ducts to the gallbladder, small intestine, and colon; this description is accompanied by descriptions of major proteins known to be involved in BA transport. Spillage of BAs into systemic circulation and urine excretion are also discussed. Finally, the review also points out some of the less-studied areas of the enterohepatic circulation, which can be crucial for the development of BA-related drugs, prodrugs, and drug carrier systems.

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Yawer A., Sychrová E., Raška J., Babica P., Sovadinová I.* (2022): Endocrine-disrupting chemicals affect Sertoli TM4 cell functionality through dysregulation of gap junctional intercellular communication in vitro. Food and Chemical Toxicology 164:113004.
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Tanabe S.*, O'Brien J., Tollefsen K. E., Kim Y., Chauhan V., Yauk C., Huliganga E., Rudel R. A., Kay J. E., Helm J. S., Beaton D., Filipovska J., Sovadinova I., Garcia-Reyero N., Mally A., Søs Poulsen S., Delrue N., Fritsche E., Luettich K., La Rocca C., Yepiskoposyan H., Klose J., Høgh Danielsen P., Esterhuizen M., Raun Jacobsen N., Vogel U., Gant T. W., Choi I., FitzGerald R. (2022): Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events. Frontiers in Toxicology 4:887135
frontiersin.org/articles/10.33

Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed as a result of natural cellular processes, intracellular signaling, or as adverse responses associated with diseases or exposure to oxidizing chemical and non-chemical stressors. The action of ROS and RNS, collectively referred to as reactive oxygen and nitrogen species (RONS), has recently become highly relevant in a number of adverse outcome pathways (AOPs) that capture, organize, evaluate and portray causal relationships pertinent to adversity or disease progression. RONS can potentially act as a key event (KE) in the cascade of responses leading to an adverse outcome (AO) within such AOPs, but are also known to modulate responses of events along the AOP continuum without being an AOP event itself. A substantial discussion has therefore been undertaken in a series of workshops named “Mystery or ROS” to elucidate the role of RONS in disease and adverse effects associated with exposure to stressors such as nanoparticles, chemical, and ionizing and non-ionizing radiation. This review introduces the background for RONS production, reflects on the direct and indirect effects of RONS, addresses the diversity of terminology used in different fields of research, and provides guidance for developing a harmonized approach for defining a common event terminology within the AOP developer community.

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Tanabe S.*, Beaton D., Chauhan V., Choi I., Danielsen P. H., Delrue N., Esterhuizen M., Filipovska J., FitzGerald R., Fritsche E., Gant T., Garcia-Reyero N., Helm J., Huliganga E., Jacobsen N., Kay J. E., Kim Y.-J., Klose J., La Rocca C., Luettich K., Mally A., O’Brien J., Poulsen S. S., Rudel R. A., Sovadinova I., Tollefsen K. E., Vogel U., Yepiskoposyan H., Yauk C. (2022): Report of the 1st and 2nd Mystery of Reactive Oxygen Species Conferences. ALTEX - Alternatives to animal experimentation 39(2):336–338.
altex.org/index.php/altex/arti

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Schneider M.*, Grossi M. F., Gadara D. C., Spáčil Z., Babica P., Bláha L. (2022): Treatment of cylindrospermopsin by hydroxyl and sulfate radicals: Does degradation equal detoxification? Journal of Hazardous Materials 424(B), 127447.
sciencedirect.com/science/arti

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Negi C. K., Babica P.*, Bajard-Esner L., Bienertova-Vasku J., Tarantino G. (2022): Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease. Metabolism 126:154925.
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Martens M., Stierum R., Schymanski E.L., Evelo C.T., Aalizadeh R., Aladjov H., Arturi K., Audouze K., Babica P., Berka K., Bessems J., Blaha L., Bolton E. E., Cases M., Damalas D. E., Dave K., Dilger M., Exner T., Geerke D. P., Grafström R., Gray A., Hancock J. M., Hollert H., Jeliazkova N., Jennen D., Jourdan F., Kahlem P., Klanova J., Kleinjans J., Kondic T., Kone B., Lynch I., Maran U., Cuesta S. M., Ménager H., Neumann S., Nymark P., Oberacher H., Ramirez N., Remy S., Rocca-Serra P., Salek R. M., Sallach B., Sansone S.-A., Sanz F., Sarimveis H., Sarntivijai S., Schulze T., Slobodnik J., Spjuth O., Tedds J., Thomaidis N., Weber R. J. M., van Westen G. J. P., Wheelock C. E., Williams A. J., Witters H., Zdrazil B., Županič A., Willighagen E. L.* (2021): ELIXIR and Toxicology: a community in development. F1000 Research 10(ELIXIR):1129
f1000research.com/articles/10-

F1000Research Article: ELIXIR and Toxicology: a community in development.

Read the latest article version by Marvin Martens, Rob Stierum, Emma L. Schymanski, Chris T. Evelo, Reza Aalizadeh, Hristo Aladjov, Kasia Arturi, Karine Audouze, Pavel Babica, Karel Berka, Jos Bessems, Ludek Blaha, Evan E. Bolton, Montserrat Cases, Dimitrios Ε. Damalas, Kirtan Dave, Marco Dilger, Thomas Exner, Daan P. Geerke, Roland Grafström, Alasdair Gray, John M. Hancock, Henner Hollert, Nina Jeliazkova, Danyel Jennen, Fabien Jourdan, Pascal Kahlem, Jana Klanova, Jos Kleinjans, Todor Kondic, Boï Kone, Iseult Lynch, Uko Maran, Sergio Martinez Cuesta, Hervé Ménager, Steffen Neumann, Penny Nymark, Herbert Oberacher, Noelia Ramirez, Sylvie Remy, Philippe Rocca-Serra, Reza M. Salek, Brett Sallach, Susanna-Assunta Sansone, Ferran Sanz, Haralambos Sarimveis, Sirarat Sarntivijai, Tobias Schulze, Jaroslav Slobodnik, Ola Spjuth, Jonathan Tedds, Nikolaos Thomaidis, Ralf J.M. Weber, Gerard J.P. van Westen, Craig E. Wheelock, Antony J. Williams, Hilda Witters, Barbara Zdrazil, Anže Županič, Egon L. Willighagen, at F1000Research.

f1000research.com
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Bláhová L., Sehnal L., Lepšová-Skácelová O., Szmucová V. Babica P., Hilscherová K., Teikari J., Sivonen K., Bláha L.* (2021): Occurrence of cylindrospermopsin, anatoxin-a and their homologs in the Czech Republic freshwaters – taxonomical, analytical, and molecular approaches.
sciencedirect.com/science/arti

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Sovadinová I., Upham B.L., Trosko J. E., Babica P.* (2021): Applicability of scrape loading-dye transfer assay for non-genotoxic carcinogen testing. International Journal of Molecular Sciences 22(16):8977.
mdpi.com/1422-0067/22/16/8977

Applicability of Scrape Loading-Dye Transfer Assay for Non-Genotoxic Carcinogen Testing

Dysregulation of gap junction intercellular communication (GJIC) is recognized as one of the key hallmarks for identifying non-genotoxic carcinogens (NGTxC). Currently, there is a demand for in vitro assays addressing the gap junction hallmark, which would have the potential to eventually become an integral part of an integrated approach to the testing and assessment (IATA) of NGTxC. The scrape loading-dye transfer (SL-DT) technique is a simple assay for the functional evaluation of GJIC in various in vitro cultured mammalian cells and represents an interesting candidate assay. Out of the various techniques for evaluating GJIC, the SL-DT assay has been used frequently to assess the effects of various chemicals on GJIC in toxicological and tumor promotion research. In this review, we systematically searched the existing literature to gather papers assessing GJIC using the SL-DT assay in a rat liver epithelial cell line, WB-F344, after treating with chemicals, especially environmental and food toxicants, drugs, reproductive-, cardio- and neuro-toxicants and chemical tumor promoters. We discuss findings derived from the SL-DT assay with the known knowledge about the tumor-promoting activity and carcinogenicity of the assessed chemicals to evaluate the predictive capacity of the SL-DT assay in terms of its sensitivity, specificity and accuracy for identifying carcinogens. These data represent important information with respect to the applicability of the SL-DT assay for the testing of NGTxC within the IATA framework.

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Mikula P., Mlnaříková M., Nadres E., Takahashi H., Babica P., Kuroda K., Bláha L., Sovadinová I.* (2021): Synthetic biomimetic polymethacrylates: Promising platform for design of anti-cyanobacterial and anti-algal agents. Polymers 13(7):1025.
mdpi.com/2073-4360/13/7/1025

Synthetic Biomimetic Polymethacrylates: Promising Platform for the Design of Anti-Cyanobacterial and Anti-Algal Agents

Extensive, uncontrolled growth of algae and cyanobacteria is an environmental, public health, economic, and technical issue in managing natural and engineered water systems. Synthetic biomimetic polymers have been almost exclusively considered antimicrobial alternatives to conventional antibiotics to treat human bacterial infections. Very little is known about their applicability in an aquatic environment. Here, we introduce synthetic biomimetic polymethacrylates (SBPs) as a cost-effective and chemically facile, flexible platform for designing a new type of agent suitable for controlling and mitigating photosynthetic microorganisms. Since SBPs are cationic and membranolytic in heterotrophic bacteria, we hypothesized they could also interact with negatively charged cyanobacterial or algal cell walls and membranes. We demonstrated that SBPs inhibited the growth of aquatic photosynthetic organisms of concern, i.e., cyanobacteria (Microcystis aeruginosa and Synechococcus elongatus) and green algae (Chlamydomonas reinhardtii and Desmodesmus quadricauda), with 50% effective growth-inhibiting concentrations ranging between 95 nM and 6.5 μM. Additionally, SBPs exhibited algicidal effects on C. reinhardtii and cyanocidal effects on picocyanobacterium S. elongatus and microcystin-producing cyanobacterium M. aeruginosa. SBP copolymers, particularly those with moderate hydrophobic content, induced more potent cyanostatic and cyanocidal effects than homopolymers. Thus, biomimetic polymers are a promising platform for the design of anti-cyanobacterial and anti-algal agents for water treatment.

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