{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:59:29Z","timestamp":1788386369435,"version":"build-2803163510"},"reference-count":215,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2020R1A2C2013373"],"award-info":[{"award-number":["2020R1A2C2013373"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Phytoplankton are prominent organisms that contain numerous bioactive substances and secondary metabolites, including toxins, which can be valuable to pharmaceutical, nutraceutical, and biotechnological industries. Studies on toxins produced by phytoplankton such as cyanobacteria, diatoms, and dinoflagellates have become more prevalent in recent years and have sparked much interest in this field of research. Because of their richness and complexity, they have great potential as medicinal remedies and biological exploratory probes. Unfortunately, such toxins are still at the preclinical and clinical stages of development. Phytoplankton toxins are harmful to other organisms and are hazardous to animals and human health. However, they may be effective as therapeutic pharmacological agents for numerous disorders, including dyslipidemia, obesity, cancer, diabetes, and hypertension. In this review, we have focused on the properties of different toxins produced by phytoplankton, as well as their beneficial effects and potential biomedical applications. The anticancer properties exhibited by phytoplankton toxins are mainly attributed to their apoptotic effects. As a result, phytoplankton toxins are a promising strategy for avoiding postponement or cancer treatment. Moreover, they also displayed promising applications in other ailments and diseases such as Alzheimer\u2019s disease, diabetes, AIDS, fungal, bacterial, schizophrenia, inflammation, allergy, osteoporosis, asthma, and pain. Preclinical and clinical applications of phytoplankton toxins, as well as future directions of their enhanced nano-formulations for improved clinical efficacy, have also been reviewed.<\/jats:p>","DOI":"10.3390\/md20040271","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T22:04:02Z","timestamp":1650319442000},"page":"271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Phytoplankton Toxins and Their Potential Therapeutic Applications: A Journey toward the Quest for Potent Pharmaceuticals"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5410-7511","authenticated-orcid":false,"given":"Biswajita","family":"Pradhan","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Sangmyung University, Seoul 03016, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6007-9262","authenticated-orcid":false,"given":"Jang-Seu","family":"Ki","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Sangmyung University, Seoul 03016, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pradhan, B., Nayak, R., Patra, S., Jit, B.P., and Ragusa, A. (2020). Bioactive Metabolites from Marine Algae as Potent Pharmacophores against Oxidative Stress-Associated Human Diseases: A Comprehensive Review. Molecules, 26.","DOI":"10.3390\/molecules26010037"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102242","DOI":"10.1016\/j.bcab.2021.102242","article-title":"Beneficial effects of seaweeds and seaweed-derived bioactive compounds: Current evidence and future prospective","volume":"39","author":"Pradhan","year":"2022","journal-title":"Biocatal. Agric. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s43094-020-00172-5","article-title":"Evaluation of the anti-bacterial activity of methanolic extract of Chlorella vulgaris Beyerinck [Beijerinck] with special reference to antioxidant modulation","volume":"7","author":"Pradhan","year":"2021","journal-title":"Future J. Pharm. Sci."},{"key":"ref_4","first-page":"107","article-title":"Bioprospecting of marine organisms for novel bioactive compounds","volume":"1","author":"Kathiresan","year":"2008","journal-title":"Sci. Trans. Environ. Technovation"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Motuhi, S.-E., Mehiri, M., Payri, C.E., La Barre, S., and Bach, S. (2016). Marine natural products from new caledonia\u2014A review. Mar. Drugs, 14.","DOI":"10.3390\/md14030058"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pradhan, B., Maharana, S., Bhakta, S., and Jena, M. (2021). Marine phytoplankton diversity of Odisha coast, India with special reference to new record of diatoms and dinoflagellates. Vegetos.","DOI":"10.1007\/s42535-021-00301-2"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.5958\/2455-7218.2021.00019.X","article-title":"Algal Diversity of Saltpans, Huma (Ganjam), India","volume":"101","author":"Behera","year":"2021","journal-title":"J. Indian Bot. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5958\/2455-7218.2021.00008.5","article-title":"Algal Flora of Tampara Lake, Chhatrapur, Odisha, India","volume":"101","author":"Dash","year":"2021","journal-title":"J. Indian Bot. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5958\/2455-7218.2020.00009.1","article-title":"Algal Diversity of Kanjiahata Lake, Nandankanan, Odisha, India","volume":"99","author":"Dash","year":"2020","journal-title":"J. Indian Bot. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"207","DOI":"10.20324\/nelumbo\/v62\/2020\/151834","article-title":"Algal Diversity of Ansupa lake, Odisha, India","volume":"62","author":"Behera","year":"2020","journal-title":"Nelumbo"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pradhan, B., Patra, S., Behera, C., Nayak, R., Jit, B.P., and Ragusa, A. (2021). Preliminary Investigation of the Antioxidant, Anti-Diabetic, and Anti-Inflammatory Activity of Enteromorpha intestinalis Extracts. Molecules, 26.","DOI":"10.3390\/molecules26041171"},{"key":"ref_12","first-page":"1","article-title":"Screening for nutritive bioactive compounds in some algal strains isolated from coastal Odisha","volume":"10","author":"Mohanty","year":"2020","journal-title":"J. Adv. Plant Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pradhan, B., Nayak, R., Patra, S., Bhuyan, P.P., Dash, S.R., Ki, J.-S., Adhikary, S.P., Ragusa, A., and Jena, M. (2022). Cyanobacteria and Algae-Derived Bioactive Metabolites as Antiviral Agents: Evidence, Mode of Action, and Scope for Further Expansion; A Comprehensive Review in Light of the SARS-CoV-2 Outbreak. Antioxidants, 11.","DOI":"10.3390\/antiox11020354"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, H., Park, H., Wang, H., Yoo, H.Y., Park, J., and Ki, J.-S. (2021). Low Temperature and Cold Stress Significantly Increase Saxitoxins (STXs) and Expression of STX Biosynthesis Genes sxtA4 and sxtG in the Dinoflagellate Alexandrium Catenella. Mar. Drugs, 19.","DOI":"10.3390\/md19060291"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bui, Q.T.N., Kim, H., Park, H., and Ki, J.-S. (2021). Salinity Affects Saxitoxins (STXs) Toxicity in the Dinoflagellate Alexandrium pacificum, with Low Transcription of SXT-Biosynthesis Genes sxtA4 and sxtG. Toxins, 13.","DOI":"10.3390\/toxins13100733"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"149801","DOI":"10.1016\/j.scitotenv.2021.149801","article-title":"Temperature influences the content and biosynthesis gene expression of saxitoxins (STXs) in the toxigenic dinoflagellate Alexandrium Pac","volume":"802","author":"Wang","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3390\/md6020349","article-title":"Neurotoxins from marine dinoflagellates: A brief review","volume":"6","author":"Wang","year":"2008","journal-title":"Mar. Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9567","DOI":"10.1007\/s11033-020-06010-4","article-title":"Enteromorpha compressa extract induces anticancer activity through apoptosis and autophagy in oral cancer","volume":"47","author":"Pradhan","year":"2020","journal-title":"Mol. Biol. Rept."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1016\/j.ijbiomac.2020.09.019","article-title":"Multifunctional role of fucoidan, sulfated polysaccharides in human health and disease: A journey under the sea in pursuit of potent therapeutic agents","volume":"164","author":"Pradhan","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","first-page":"e00633","article-title":"Chemical diversity of dietary phytochemicals and their mode of chemoprevention","volume":"30","author":"Patra","year":"2021","journal-title":"Biotechnol. Rep. (Amst. Neth.)"},{"key":"ref_21","first-page":"153554","article-title":"Dietary polyphenols in chemoprevention and synergistic effect in cancer: Clinical evidences and molecular mechanisms of action","volume":"90","author":"Patra","year":"2021","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4194","DOI":"10.1002\/ptr.7082","article-title":"Apoptosis and autophagy modulating dietary phytochemicals in cancer therapeutics: Current evidences and future perspectives","volume":"35","author":"Patra","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.semcancer.2020.10.010","article-title":"Chemotherapeutic efficacy of curcumin and resveratrol against cancer: Chemoprevention, chemoprotection, drug synergism and clinical pharmacokinetics","volume":"73","author":"Patra","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_24","first-page":"737","article-title":"Diversity of Phytoplankton in Chilika Lagoon, Odisha, India","volume":"37","author":"Maharana","year":"2019","journal-title":"Environ. Ecol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.3390\/md11072239","article-title":"Interpreting the possible ecological role(s) of cyanotoxins: Compounds for competitive advantage and\/or physiological aide?","volume":"11","author":"Holland","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1080\/109374000436364","article-title":"Health risks caused by freshwater cyanobacteria in recreational waters","volume":"3","author":"Chorus","year":"2000","journal-title":"J. Toxicol. Environ. Health Part B Crit. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/mnfr.200600185","article-title":"Toxins of cyanobacteria","volume":"51","author":"Speijers","year":"2007","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1017\/S0025315415001733","article-title":"Marine harmful algal blooms, human health and wellbeing: Challenges and opportunities in the 21st century","volume":"96","author":"Berdalet","year":"2016","journal-title":"J. Mar. Biol. Assoc. United Kingd."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3390\/ijms11010268","article-title":"Molecular mechanisms of microcystin toxicity in animal cells","volume":"11","author":"Campos","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-5793(03)01447-9","article-title":"Microcystin-LR and okadaic acid-induced cellular effects: A dualistic response","volume":"557","author":"Gehringer","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.toxicon.2008.10.027","article-title":"In vivo study on the effects of microcystin extracts on the expression profiles of proto-oncogenes (c-fos, c-jun and c-myc) in liver, kidney and testis of male Wistar rats injected iv with toxins","volume":"53","author":"Li","year":"2009","journal-title":"Toxicon"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.tiv.2010.05.018","article-title":"Microcystin-LR activates the ERK1\/2 kinases and stimulates the proliferation of the monkey kidney-derived cell line Vero-E6","volume":"24","author":"Dias","year":"2010","journal-title":"Toxicology In Vitro"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.mrrev.2011.01.002","article-title":"Genotoxicity and potential carcinogenicity of cyanobacterial toxins\u2014A review","volume":"727","year":"2011","journal-title":"Mutat. Res.\/Rev. Mutat. Res."},{"key":"ref_34","unstructured":"Burch, M.D. (2008). Effective doses, guidelines & regulations. Cyanobacterial Harmful Algal Blooms: State of the Science and Research Needs, Springer."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.toxicon.2013.09.008","article-title":"Spatial and thematic distribution of research on cyanotoxins","volume":"76","author":"Merel","year":"2013","journal-title":"Toxicon"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4594","DOI":"10.3390\/md11114594","article-title":"Bioprospecting marine plankton","volume":"11","author":"Abida","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_37","first-page":"69","article-title":"The value of plants used in traditional medicine for drug discovery","volume":"109","author":"Fabricant","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fmars.2016.00068","article-title":"Bioactivity screening of microalgae for antioxidant, anti-inflammatory, anticancer, anti-diabetes, and antibacterial activities","volume":"3","author":"Lauritano","year":"2016","journal-title":"Front. Mar. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1056\/NEJM199104253241707","article-title":"Therapeutic uses of botulinum toxin","volume":"324","author":"Jankovic","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"258","DOI":"10.7861\/clinmedicine.4-3-258","article-title":"The story of Clostridium botulinum: From food poisoning to Botox","volume":"4","author":"Ting","year":"2004","journal-title":"Clin. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s10549-005-6942-4","article-title":"Anti-estrogenic effects of conjugated linoleic acid through modulation of estrogen receptor phosphorylation","volume":"94","author":"Liu","year":"2005","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4328","DOI":"10.3390\/md11114328","article-title":"Okadaic acid: More than a diarrheic toxin","volume":"11","author":"Valdiglesias","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15366","DOI":"10.1074\/jbc.272.24.15366","article-title":"Stimulation of interleukin-8 production by okadaic acid and vanadate in a human promyelocyte cell line, an HL-60 subline: Possible role of mitogen-activated protein kinase on the okadaic acid-induced NF-\u03baB activation","volume":"272","author":"Sonoda","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.canlet.2008.10.034","article-title":"Okadaic acid promotes angiogenesis via activation of hypoxia-inducible factor-1","volume":"276","author":"Kim","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1039\/b310427n","article-title":"Amphidinolides, bioactive macrolides from symbiotic marine dinoflagellates","volume":"21","author":"Kobayashi","year":"2004","journal-title":"Nat. Prod. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/S0041-0101(00)00255-5","article-title":"Toxic marine microalgae","volume":"39","author":"Daranas","year":"2001","journal-title":"Toxicon"},{"key":"ref_48","first-page":"543","article-title":"Amphidinolides: Unique macrolides from marine dinoflagellates","volume":"1","author":"Ishibashi","year":"1997","journal-title":"Heterocycles"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1021\/ol025814u","article-title":"Studies toward the Total Synthesis of Gymnocin A, a Cytotoxic Polyether: A Highly Convergent Entry to the F\u2013N Ring Fragment","volume":"4","author":"Sasaki","year":"2002","journal-title":"Org. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/sj.bjc.6601640","article-title":"Selective disruption of the E-cadherin-catenin system by an algal toxin","volume":"90","author":"Ronzitti","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Alfonso, A., Vieytes, M.R., and Botana, L.M. (2016). Yessotoxin, a promising therapeutic tool. Mar. Drugs, 14.","DOI":"10.3390\/md14020030"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fcell.2017.00030","article-title":"Mitotic catastrophe in BC3H1 cells following yessotoxin exposure","volume":"5","author":"Korsnes","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1021\/np040008c","article-title":"Highly Cytotoxic Metabolites from the Culture Supernatant of the Temperate Dinoflagellate Protoceratium cf.  r eticulatum","volume":"67","author":"Konishi","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/np50125a012","article-title":"Cytotoxic compounds from a two-sponge association","volume":"58","author":"Jung","year":"1995","journal-title":"J. Nat. Prod."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0022-510X(91)90021-X","article-title":"Effects of ciguatoxin on nerve excitability in rats (Part I)","volume":"101","author":"Cameron","year":"1991","journal-title":"J. Neurol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0022-510X(91)90022-Y","article-title":"Electrophysiological studies on ciguatera poisoning in man (Part II)","volume":"101","author":"Cameron","year":"1991","journal-title":"J. Neurol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3390\/md6020291","article-title":"Effects of in vitro brevetoxin exposure on apoptosis and cellular metabolism in a leukemic T cell line (Jurkat)","volume":"6","author":"Walsh","year":"2008","journal-title":"Mar. Drugs"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1007\/s00204-009-0443-x","article-title":"Brevetoxins 2, 3, 6, and 9 show variability in potency and cause significant induction of DNA damage and apoptosis in Jurkat E6-1 cells","volume":"83","author":"Murrell","year":"2009","journal-title":"Arch. Toxicol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s11596-015-1506-3","article-title":"Toxic potential of palytoxin","volume":"35","author":"Patocka","year":"2015","journal-title":"J. Huazhong Univ. Sci. Technol. [Med. Sci.]"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Louzao, M.C., Fraga, M., and Vilari\u00f1o, N. (2015). Pharmacology of palytoxins and ostreocins. Phycotoxins, Chemistry and Biochemistry, John Wiley & Sons, Ltd.","DOI":"10.1002\/9781118500354.ch6"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.3390\/md8072021","article-title":"Palytoxin and analogs: Biological and ecological effects","volume":"8","author":"Ramos","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1021\/tx3001785","article-title":"Induction of apoptosis pathways in several cell lines following exposure to the marine algal toxin azaspiracid","volume":"25","author":"Twiner","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ygeno.2007.10.015","article-title":"Transcriptional profiling and inhibition of cholesterol biosynthesis in human T lymphocyte cells by the marine toxin azaspiracid","volume":"91","author":"Twiner","year":"2008","journal-title":"Genomics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6803","DOI":"10.1016\/j.tetlet.2006.07.081","article-title":"Structure\u2014Activity relationship studies of gymnocin-A","volume":"47","author":"Tsukano","year":"2006","journal-title":"Tetrahedron Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.copbio.2010.09.013","article-title":"The expanding role of marine microbes in pharmaceutical development","volume":"21","author":"Waters","year":"2010","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"15931","DOI":"10.1002\/ange.201507418","article-title":"Stereochemical Studies of the Karlotoxin Class Using NMR Spectroscopy and DP4 Chemical-Shift Analysis: Insights into their Mechanism of Action","volume":"127","author":"Waters","year":"2015","journal-title":"Angew. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.etap.2005.02.008","article-title":"Investigations into the cellular actions of the shellfish toxin gymnodimine and analogues","volume":"20","author":"Dragunow","year":"2005","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.neuro.2013.05.002","article-title":"Okadaic acid induced neurotoxicity: An emerging tool to study Alzheimer\u2019s disease pathology","volume":"37","author":"Kamat","year":"2013","journal-title":"Neurotoxicology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-\u03b2 and tau: The trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_70","unstructured":"L\u00f3pez, L.M.B., L\u00f3pez, E.A., and Gonz\u00e1lez, C.V. (2012). Use of Gambierol for Treating and\/or Preventing Neurodegenerative Diseases Related to Tau and Beta-Amyloid. (13\/504,825), U.S. Patent."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1159\/000330086","article-title":"The cholinergic antagonist gymnodimine improves A\u03b2 and tau neuropathology in an in vitro model of Alzheimer disease","volume":"27","author":"Alonso","year":"2011","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.neuint.2011.08.013","article-title":"13-Desmethyl spirolide-C is neuroprotective and reduces intracellular A\u03b2 and hyperphosphorylated tau in vitro","volume":"59","author":"Alonso","year":"2011","journal-title":"Neurochem. Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s10350-004-0893-4","article-title":"Gonyautoxin: New treatment for healing acute and chronic anal fissures","volume":"48","author":"Garrido","year":"2005","journal-title":"Dis. Colon Rectum"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1179\/174313209X380829","article-title":"Local infiltration of gonyautoxin is safe and effective in treatment of chronic tension-type headache","volume":"31","author":"Lattes","year":"2009","journal-title":"Neurol. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/sj.npp.1300757","article-title":"Olanzapine attenuates the okadaic acid-induced spatial memory impairment and hippocampal cell death in rats","volume":"30","author":"He","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6859","DOI":"10.1128\/jvi.69.11.6859-6864.1995","article-title":"Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B","volume":"69","author":"Re","year":"1995","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.3390\/toxins7051749","article-title":"Toxins targeting the Kv1. 3 channel: Potential immunomodulators for autoimmune diseases","volume":"7","author":"Zhao","year":"2015","journal-title":"Toxins"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"17414","DOI":"10.1073\/pnas.0605136103","article-title":"Kv1. 3 channels are a therapeutic target for T cell-mediated autoimmune diseases","volume":"103","author":"Beeton","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/BF02180919","article-title":"Antimicrobial activities of polyether compounds of dinoflagellate origins","volume":"2","author":"Nagai","year":"1990","journal-title":"J. Appl. Phycol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bbamem.2004.09.002","article-title":"Membrane-permeabilizing activities of amphidinol 3, polyene-polyhydroxy antifungal from a marine dinoflagellate","volume":"1667","author":"Houdai","year":"2004","journal-title":"Biochim. Biophys. Acta-Biomembr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.hal.2007.10.003","article-title":"Characterization and quantification of karlotoxins by liquid chromatography\u2013mass spectrometry","volume":"7","author":"Bachvaroff","year":"2008","journal-title":"Harmful Algae"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.aquatox.2014.11.028","article-title":"The cytotoxic mechanism of karlotoxin 2 (KmTx 2) from Karlodinium veneficum (Dinophyceae)","volume":"159","author":"Deeds","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Tob\u00edo, A., Alfonso, A., Madera-Salcedo, I., Botana, L.M., and Blank, U. (2016). Yessotoxin, a marine toxin, exhibits anti-allergic and anti-tumoural activities inhibiting melanoma tumour growth in a preclinical model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167572"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"19840","DOI":"10.1073\/pnas.1212584109","article-title":"Bidirectional influence of sodium channel activation on NMDA receptor\u2013dependent cerebrocortical neuron structural plasticity","volume":"109","author":"George","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kita, M., and Uemura, D. (2006). Bioactive heterocyclic alkaloids of marine origin. Bioactive Heterocycles I., Springer.","DOI":"10.1007\/7081_039"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kita, M., Inuzuka, T., Maru, N., and Uemura, D. (2012). 12 Bioactive Molecules from Symbiotic Marine Dinoflagellates. Marine Pharmacognosy: Trends and Applications, CRC Press.","DOI":"10.1201\/b13868-13"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1124\/jpet.114.215319","article-title":"Gambierol inhibition of voltage-gated potassium channels augments spontaneous Ca2+ oscillations in cerebrocortical neurons","volume":"350","author":"Cao","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/BF00003544","article-title":"Microalgae as sources of pharmaceuticals and other biologically active compounds","volume":"7","author":"Borowitzka","year":"1995","journal-title":"J. Appl. Phycol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"179782","DOI":"10.1100\/2012\/179782","article-title":"Exploring marine cyanobacteria for lead compounds of pharmaceutical importance","volume":"2012","author":"Uzair","year":"2012","journal-title":"Sci. World J."},{"key":"ref_90","first-page":"S554","article-title":"Antimicrobial Activity of Nostoc calcicola (Cyanobacteria) isolated from central India against human pathogens","volume":"10","author":"Yadav","year":"2016","journal-title":"Asian J. Pharm."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Shah, S.A.A., Akhter, N., Auckloo, B.N., Khan, I., Lu, Y., Wang, K., Wu, B., and Guo, Y.-W. (2017). Structural diversity, biological properties and applications of natural products from cyanobacteria. A review. Mar. Drugs, 15.","DOI":"10.3390\/md15110354"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Pradhan, B., Patra, S., Dash, S.R., Satapathy, Y., Nayak, S., Mandal, A.K., and Jena, M. (2022). In vitro antidiabetic, anti-inflammatory and antibacterial activity of marine alga Enteromorpha compressa collected from Chilika lagoon, Odisha, India. Vegetos.","DOI":"10.1007\/s42535-022-00359-6"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Mondal, A., Bose, S., Banerjee, S., Patra, J.K., Malik, J., Mandal, S.K., Kilpatrick, K.L., Das, G., Kerry, R.G., and Fimognari, C. (2020). Marine cyanobacteria and microalgae metabolites\u2014A rich source of potential anticancer drugs. Mar. Drugs, 18.","DOI":"10.3390\/md18090476"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Singh, S.K., Kaur, R., Bansal, A., Kapur, S., and Sundaram, S. (2020). Biotechnological exploitation of cyanobacteria and microalgae for bioactive compounds. Biotechnological Production of Bioactive Compounds, Elsevier.","DOI":"10.1016\/B978-0-444-64323-0.00008-4"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/jat.1717","article-title":"A review of pharmacological and toxicological potentials of marine cyanobacterial metabolites","volume":"32","author":"Nagarajan","year":"2012","journal-title":"J. Appl. Toxicol."},{"key":"ref_96","first-page":"214186","article-title":"Anticancer drugs from marine flora: An overview","volume":"2010","author":"Kathiresan","year":"2010","journal-title":"J. Oncol."},{"key":"ref_97","first-page":"611","article-title":"Bioactive potency of cyanobacteria Oscillatoria spp.","volume":"5","author":"Nair","year":"2013","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s11101-009-9120-1","article-title":"Marine natural products as inhibitors of hypoxic signaling in tumors","volume":"8","author":"Nagle","year":"2009","journal-title":"Phytochem. Rev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.3390\/md8102659","article-title":"Marine benthic cyanobacteria contain apoptosis-inducing activity synergizing with daunorubicin to kill leukemia cells, but not cardiomyocytes","volume":"8","author":"Oftedal","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.2042-7158.1998.tb06899.x","article-title":"Goniodomin A, an antifungal polyether macrolide, increases the filamentous actin content of 1321N1 human astrocytoma cells","volume":"50","author":"Mizuno","year":"1998","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"7594","DOI":"10.1039\/C9RA00965E","article-title":"Chemical and biological study of aplysiatoxin derivatives showing inhibition of potassium channel Kv1. 5","volume":"9","author":"Tang","year":"2019","journal-title":"Rsc Adv."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1039\/b404205k","article-title":"Total synthesis and biological evaluation of (+)-kalkitoxin, a cytotoxic metabolite of the cyanobacterium Lyngbya majuscula","volume":"2","author":"White","year":"2004","journal-title":"Org. Biomol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.toxlet.2005.03.007","article-title":"The neurotoxic lipopeptide kalkitoxin interacts with voltage-sensitive sodium channels in cerebellar granule neurons","volume":"158","author":"LePage","year":"2005","journal-title":"Toxicol. Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0300-483X(03)00112-4","article-title":"Comparative toxicity evaluation of cyanobacterial cyclic peptide toxin microcystin variants (LR, RR, YR) in mice","volume":"188","author":"Gupta","year":"2003","journal-title":"Toxicology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"629","DOI":"10.3390\/md8030629","article-title":"Cyanobacterial cyclopeptides as lead compounds to novel targeted cancer drugs","volume":"8","author":"Sainis","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/S0041-0101(98)00128-7","article-title":"The cyanobacterial toxin, microcystin-LR, can induce apoptosis in a variety of cell types","volume":"36","author":"McDermott","year":"1998","journal-title":"Toxicon"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/sj.cdd.4400590","article-title":"Ultrarapid caspase-3 dependent apoptosis induction by serine\/threonine phosphatase inhibitors","volume":"6","author":"Fladmark","year":"1999","journal-title":"Cell Death Differ."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/tox.1028","article-title":"Apoptotic effect of cyanobacterial extract on rat hepatocytes and human lymphocytes","volume":"16","author":"Mankiewicz","year":"2001","journal-title":"Environ. Toxicol. Int. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.neuro.2010.05.003","article-title":"Domoic acid as a developmental neurotoxin","volume":"31","author":"Costa","year":"2010","journal-title":"Neurotoxicology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.3390\/ijerph120504921","article-title":"Molecular detection of a potentially toxic diatom species","volume":"12","author":"Dhar","year":"2015","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.algal.2015.11.020","article-title":"Environmental roles and biological activity of domoic acid: A review","volume":"13","author":"Zabaglo","year":"2016","journal-title":"Algal Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1046\/j.1529-8817.2000.03661.x","article-title":"Domoic-acid-producing diatoms: Another genus added!","volume":"36","author":"Bates","year":"2000","journal-title":"J. Phycol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Olesen, A.J., Leithoff, A., Altenburger, A., Krock, B., Beszteri, B., Eggers, S.L., and Lundholm, N. (2021). First Evidence of the Toxin Domoic Acid in Antarctic Diatom Species. Toxins, 13.","DOI":"10.3390\/toxins13020093"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1444-2906.2003.00766.x","article-title":"Wide distribution of Nitzschia navis-varingica, a new domoic acid-producing benthic diatom found in Vietnam","volume":"70","author":"Kotaki","year":"2004","journal-title":"Fish. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1021\/tx0496845","article-title":"Isodomoic acid C, an unusual amnesic shellfish poisoning toxin from Pseudo-Nitzschia australis","volume":"18","author":"Holland","year":"2005","journal-title":"Chem. Res. Toxicol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.hal.2011.02.006","article-title":"Unique amnesic shellfish toxin composition found in the South East Asian diatom Nitzschia Navis-Varingica","volume":"10","author":"Romero","year":"2011","journal-title":"Harmful Algae"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"168","DOI":"10.2216\/11-37.1","article-title":"Pseudo-nitzschia (Bacillariophyceae) species, domoic acid and amnesic shellfish poisoning: Revisiting previous paradigms","volume":"51","author":"Lelong","year":"2012","journal-title":"Phycologia"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1080\/16583655.2018.1451107","article-title":"Proliferative effect of the phycotoxin domoic acid on cancer cell lines: A preliminary evaluation","volume":"12","author":"Ayed","year":"2018","journal-title":"J. Taibah Univ. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1890\/1051-0761(1998)8[S37:IOHMAH]2.0.CO;2","article-title":"Implications of harmful microalgae and heterotrophic dinoflagellates in management of sustainable marine fisheries","volume":"8","author":"Burkholder","year":"1998","journal-title":"Ecol. Appl."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3390\/md6020073","article-title":"Yessotoxins, a group of marine polyether toxins: An overview","volume":"6","author":"Paz","year":"2008","journal-title":"Mar. Drugs"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.hal.2005.06.008","article-title":"Yessotoxin production by Gonyaulax spinifera","volume":"5","author":"Rhodes","year":"2006","journal-title":"Harmful Algae"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1440-1681.2011.05539.x","article-title":"Tetrodotoxin alleviates acute heroin withdrawal syndrome: A multicentre, randomized, double-blind, placebo-controlled study","volume":"38","author":"Song","year":"2011","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.3390\/md8072185","article-title":"Neurotoxic alkaloids: Saxitoxin and its analogs","volume":"8","author":"Wiese","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/jcp.10040","article-title":"Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibition of actin reorganization in endothelial cells","volume":"190","author":"Abe","year":"2002","journal-title":"J. Cell. Physiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0041-0101(03)00088-6","article-title":"Type B brevetoxins show tissue selectivity for voltage-gated sodium channels: Comparison of brain, skeletal muscle and cardiac sodium channels","volume":"41","author":"Dechraoui","year":"2003","journal-title":"Toxicon"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"6384","DOI":"10.3390\/md13106384","article-title":"Tetrodotoxin, an extremely potent marine neurotoxin: Distribution, toxicity, origin and therapeutical uses","volume":"13","author":"Lago","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"229","DOI":"10.2174\/0929867023371247","article-title":"Okadaic acid, useful tool for studying cellular processes","volume":"9","author":"Fernandez","year":"2002","journal-title":"Curr. Med. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.toxlet.2011.09.007","article-title":"Immunoregulatory potential of marine algal toxins yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4","volume":"207","author":"Camacho","year":"2011","journal-title":"Toxicol. Lett."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1351\/pac200375020337","article-title":"Bioactive macrolides and polyketides from marine dinoflagellates","volume":"75","author":"Kobayashi","year":"2003","journal-title":"Pure Appl. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1016\/S0040-4039(01)81076-5","article-title":"Isolation and structure of yessotoxin, a novel polyether compound implicated in diarrhetic shellfish poisoning","volume":"28","author":"Murata","year":"1987","journal-title":"Tetrahedron Lett."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.toxicon.2011.03.012","article-title":"Yessotoxin as an apoptotic inducer","volume":"57","author":"Korsnes","year":"2011","journal-title":"Toxicon"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.tox.2015.01.004","article-title":"Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin","volume":"329","author":"Alfonso","year":"2015","journal-title":"Toxicology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.toxicon.2009.07.033","article-title":"Yessotoxin inhibits phagocytic activity of macrophages","volume":"55","author":"Orsi","year":"2010","journal-title":"Toxicon"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.tiv.2006.07.012","article-title":"Cleavage of tensin during cytoskeleton disruption in YTX-induced apoptosis","volume":"21","author":"Korsnes","year":"2007","journal-title":"Toxicology In Vitro"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cellsig.2013.10.004","article-title":"Yessotoxin induces ER-stress followed by autophagic cell death in glioma cells mediated by mTOR and BNIP3","volume":"26","author":"Rubiolo","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"878","DOI":"10.3390\/toxins2040878","article-title":"Marine toxins: Chemistry, toxicity, occurrence and detection, with special reference to the Dutch situation","volume":"2","author":"Gerssen","year":"2010","journal-title":"Toxins"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1021\/tx9002337","article-title":"Impact of the pectenotoxin C-43 oxidation degree on its cytotoxic effect on rat hepatocytes","volume":"23","author":"Espina","year":"2010","journal-title":"Chem. Res. Toxicol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4813","DOI":"10.1038\/sj.onc.1208640","article-title":"Oocyte-based screening of cytokinesis inhibitors and identification of pectenotoxin-2 that induces Bim\/Bax-mediated apoptosis in p53-deficient tumors","volume":"24","author":"Chae","year":"2005","journal-title":"Oncogene"},{"key":"ref_139","first-page":"8","article-title":"The origin of ciguatera\u2014An update","volume":"2","author":"Holmes","year":"1992","journal-title":"Ciguatera Inf. Bull. Noumea"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.toxicon.2014.09.016","article-title":"The voltage-gated sodium channel: A major target of marine neurotoxins","volume":"91","author":"Mattei","year":"2014","journal-title":"Toxicon"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1093\/brain\/aws225","article-title":"Neurological perspectives on voltage-gated sodium channels","volume":"135","author":"Eijkelkamp","year":"2012","journal-title":"Brain"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/ijch.201190005","article-title":"Cover Picture: Maitotoxin: An Inspiration for Synthesis (Isr. J. Chem. 3-4\/2011)","volume":"51","author":"Nicolaou","year":"2011","journal-title":"Isr. J. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"25025","DOI":"10.1016\/S0021-9258(19)74000-9","article-title":"Maitotoxin induces a calcium-dependent membrane depolarization in GH4C1 pituitary cells via activation of type L voltage-dependent calcium channels","volume":"267","author":"Xi","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_144","unstructured":"Reyes, J.G., S\u00e1nchez-C\u00e1rdenas, C., Acevedo-Castillo, W., Leyton, P., L\u00f3pez-Gonz\u00e1lez, I., Felix, R., Gandini, M.A., Trevi\u00f1o, M.B., and Trevi\u00f1o, C.L. (2022, January 22). Maitotoxin: An enigmatic toxic molecule with useful applications in the biomedical sciences. Available online: https:\/\/www.researchgate.net\/publication\/260479283_Maitotoxin_An_Enigmatic_Toxic_Molecule_with_Useful_Applications_in_the_Biomedical_Sciences."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1093\/oxfordjournals.jbchem.a122438","article-title":"Some chemical properties of maitotoxin, a putative calcium channel agonist isolated from a marinedinoflagellate","volume":"104","author":"Yokoyama","year":"1988","journal-title":"J. Biochem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.hal.2014.07.018","article-title":"Production of ciguatoxin and maitotoxin by strains of Gambierdiscus australes, G. pacificus and G. polynesiensis (Dinophyceae) isolated from Rarotonga, Cook Islands","volume":"39","author":"Rhodes","year":"2014","journal-title":"Harmful Algae"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/0006-8993(86)90088-0","article-title":"Maitotoxin and Bay-K-8644: Two putative calcium channel activators with different effects on endogenous dopamine release from tuberoinfundibular neurons","volume":"381","author":"Taglialatela","year":"1986","journal-title":"Brain Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0014-5793(88)81371-1","article-title":"Differential effects of maitotoxin on ATP secretion and on phosphoinositide breakdown in rat pheochromocytoma cells","volume":"233","author":"Gusovsky","year":"1988","journal-title":"FEBS Lett."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6793-1-2","article-title":"Maitotoxin-induced membrane blebbing and cell death in bovine aortic endothelial cells","volume":"1","author":"Estacion","year":"2001","journal-title":"BMC Physiol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1124\/mol.66.4.909","article-title":"Maitotoxin induces biphasic interleukin-1\u03b2 secretion and membrane blebbing in murine macrophages","volume":"66","author":"Verhoef","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1038\/sj.bjp.0702706","article-title":"Maitotoxin-induced nerve growth factor production accompanied by the activation of a voltage-insensitive Ca2+ channel in C6-BU-1 glioma cells","volume":"127","author":"Obara","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Flores, P.L., Rodr\u00edguez, E., Zapata, E., Carb\u00f3, R., Far\u00edas, J.M., and Mart\u00ednez, M. (2017). Maitotoxin Is a potential selective activator of the endogenous transient receptor potential canonical Type 1 channel in Xenopus laevis oocytes. Mar. Drugs, 15.","DOI":"10.3390\/md15070198"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1096\/fasebj.3.7.2565840","article-title":"Brevetoxins: Unique polyether dinoflagellate toxins","volume":"3","author":"Baden","year":"1989","journal-title":"FASEB J."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.toxicon.2009.11.007","article-title":"Advances in monitoring and toxicity assessment of brevetoxins in molluscan shellfish","volume":"56","author":"Plakas","year":"2010","journal-title":"Toxicon"},{"key":"ref_155","first-page":"1","article-title":"Harmful algal blooms: A global overview","volume":"33","author":"Hallegraeff","year":"2003","journal-title":"Man. Harmful Mar. Microalgae"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1164\/rccm.200406-735OC","article-title":"Airway responses to aerosolized brevetoxins in an animal model of asthma","volume":"171","author":"Abraham","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00204-010-0564-2","article-title":"Marine brevetoxin induces IgE-independent mast cell activation","volume":"85","author":"Hilderbrand","year":"2011","journal-title":"Arch. Toxicol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.ijheh.2010.06.007","article-title":"Brevetoxin-2 induces an inflammatory response in an alveolar macrophage cell line","volume":"213","author":"Sas","year":"2010","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_159","unstructured":"Baden, D.G., Abraham, W.M., and Bourdelais, A.J. (2008). Polyether Brevetoxin Derivatives as a Treatment for Cystic Fibrosis, Mucociliary Dysfunction, and Pulmonary Diseases. (7,399,782), U.S. Patent."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.ntt.2005.06.012","article-title":"Effects of marine algal toxins on thermoregulation in mice","volume":"27","author":"Gordon","year":"2005","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/tcr.200900007","article-title":"Bioactive secondary metabolites from symbiotic marine dinoflagellates: Symbiodinolide and durinskiols","volume":"10","author":"Kita","year":"2010","journal-title":"Chem. Rec."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"658","DOI":"10.3390\/md8030658","article-title":"Targets and effects of yessotoxin, okadaic acid and palytoxin: A differential review","volume":"8","author":"Franchini","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Assun\u00e7\u00e3o, J., Guedes, A.C., and Malcata, F.X. (2017). Biotechnological and pharmacological applications of biotoxins and other bioactive molecules from dinoflagellates. Mar. Drugs, 15.","DOI":"10.3390\/md15120393"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1039\/C6TX00084C","article-title":"Pro-inflammatory effects of palytoxin: An in vitro study on human keratinocytes and inflammatory cells","volume":"5","author":"Pelin","year":"2016","journal-title":"Toxicol. Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1021\/ja00054a061","article-title":"Gambierol: A new toxic polyether compound isolated from the marine dinoflagellate Gambierdiscus toxicus","volume":"115","author":"Satake","year":"1993","journal-title":"J. Am. Chem. Soc."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fchem.2014.00116","article-title":"Concise synthesis of the A\/BCD-ring fragment of gambieric acid A","volume":"2","author":"Fuwa","year":"2015","journal-title":"Front. Chem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"14070","DOI":"10.1021\/es403175d","article-title":"Pacific ciguatoxins in food web components of coral reef systems in the Republic of Kiribati","volume":"47","author":"Mak","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s00204-014-1299-2","article-title":"Potassium currents inhibition by gambierol analogs prevents human T lymphocyte activation","volume":"89","author":"Rubiolo","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Alonso, E., and Rubiolo, J.A. (2015). Therapeutics of marine toxins. Phycotoxins Chem. Biochem., 181\u2013201.","DOI":"10.1002\/9781118500354.ch8"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1124\/jpet.107.124271","article-title":"Gambierol acts as a functional antagonist of neurotoxin site 5 on voltage-gated sodium channels in cerebellar granule neurons","volume":"323","author":"LePage","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"420","DOI":"10.2216\/i0031-8884-42-4-420.1","article-title":"Chemical ecology of eukaryotic microalgae in marine ecosystems","volume":"42","author":"Cembella","year":"2003","journal-title":"Phycologia"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/09670260802578534","article-title":"Azadinium spinosum gen. et sp. nov.(Dinophyceae) identified as a primary producer of azaspiracid toxins","volume":"44","author":"Tillmann","year":"2009","journal-title":"Eur. J. Phycol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1111\/jpy.12104","article-title":"A new potentially toxic A. zadinium species (D inophyceae) from the M editerranean Sea, A. dexteroporum sp. nov","volume":"49","author":"Percopo","year":"2013","journal-title":"J. Phycol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.hal.2016.02.012","article-title":"Toxigenic algae and associated phycotoxins in two coastal embayments in the Ebro Delta (NW Mediterranean)","volume":"55","author":"Busch","year":"2016","journal-title":"Harmful Algae"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"6075","DOI":"10.1111\/j.1742-4658.2008.06713.x","article-title":"Marine toxins and the cytoskeleton: Azaspiracids","volume":"275","year":"2008","journal-title":"FEBS J."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.toxicon.2005.02.015","article-title":"Cytotoxic and cytoskeletal effects of azaspiracid-1 on mammalian cell lines","volume":"45","author":"Twiner","year":"2005","journal-title":"Toxicon"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/toxsci\/kfp312","article-title":"Involvement of caspase activation in azaspiracid-induced neurotoxicity in neocortical neurons","volume":"114","author":"Cao","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/toxsci\/kfp246","article-title":"Cell volume decrease as a link between azaspiracid-induced cytotoxicity and c-Jun-N-terminal kinase activation in cultured neurons","volume":"113","author":"Vale","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1021\/tx0341862","article-title":"Effects of azaspiracids 2 and 3 on intracellular cAMP,[Ca2+], and pH","volume":"17","author":"Alfonso","year":"2004","journal-title":"Chem. Res. Toxicol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/bs.coac.2017.08.002","article-title":"Structural diversity of microalgal marine toxins","volume":"78","year":"2017","journal-title":"Recent Adv. Anal. Mar. Toxins. Amst. Neth. Elsevier"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.hal.2015.07.006","article-title":"Ichthyotoxic Karlodinium veneficum (Ballantine) J Larsen in the upper Swan River estuary (Western Australia): Ecological conditions leading to a fish kill","volume":"48","author":"Adolf","year":"2015","journal-title":"Harmful Algae"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2216\/i0031-8884-39-1-67.1","article-title":"The marine dinoflagellate Alexandrium ostenfeldii (Dinophyceae) as the causative organism of spirolide shellfish toxins","volume":"39","author":"Cembella","year":"2000","journal-title":"Phycologia"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.hal.2008.04.001","article-title":"Morphogenetic diversity and biotoxin composition of Alexandrium (Dinophyceae) in Irish coastal waters","volume":"7","author":"Touzet","year":"2008","journal-title":"Harmful Algae"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"4838","DOI":"10.1021\/jf030101r","article-title":"Gymnodimine C, an isomer of gymnodimine B, from Karenia selliformis","volume":"51","author":"Miles","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"7087","DOI":"10.3390\/md13127057","article-title":"Potential threats posed by new or emerging marine biotoxins in UK waters and examination of detection methodologies used for their control: Cyclic imines","volume":"13","author":"Davidson","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0161-813X(03)00014-7","article-title":"Neural injury biomarkers of novel shellfish toxins, spirolides: A pilot study using immunochemical and transcriptional analysis","volume":"24","author":"Gill","year":"2003","journal-title":"Neurotoxicology"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"7093","DOI":"10.1016\/0040-4039(95)01434-J","article-title":"Gymnodimine, a new marine toxin of unprecedented structure isolated from New Zealand oysters and the dinoflagellate, Gymnodinium sp.","volume":"36","author":"Seki","year":"1995","journal-title":"Tetrahedron Lett."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1016\/j.tetlet.2011.05.137","article-title":"Occurrence of 12-methylgymnodimine in a spirolide-producing dinoflagellate Alexandrium peruvianum and the biogenetic implications","volume":"52","author":"Misner","year":"2011","journal-title":"Tetrahedron Lett."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.toxicon.2016.01.064","article-title":"Identification of gymnodimine D and presence of gymnodimine variants in the dinoflagellate Alexandrium ostenfeldii from the Baltic Sea","volume":"112","author":"Harju","year":"2016","journal-title":"Toxicon"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"145","DOI":"10.5670\/oceanog.2018.417","article-title":"Toxigenic dinoflagellates and associated toxins in San Jorge Gulf, Argentina","volume":"31","author":"Fabro","year":"2018","journal-title":"Oceanography"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1111\/j.1471-4159.2008.05677.x","article-title":"The marine phycotoxin gymnodimine targets muscular and neuronal nicotinic acetylcholine receptor subtypes with high affinity","volume":"107","author":"Kharrat","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1055\/s-0034-1383001","article-title":"Exploring marine resources for bioactive compounds","volume":"80","author":"Kiuru","year":"2014","journal-title":"Planta Med."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1021\/ja00029a057","article-title":"Gambieric acids: Unprecedented potent antifungal substances isolated from cultures of a marine dinoflagellate Gambierdiscus toxicus","volume":"114","author":"Nagai","year":"1992","journal-title":"J. Am. Chem. Soc."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"520","DOI":"10.7164\/antibiotics.46.520","article-title":"Biological activities of novel polyether antifungals, gambieric acids A and B from a marine dinoflagellate Gambierdiscus toxicus","volume":"46","author":"Nagai","year":"1993","journal-title":"J. Antibiot."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0041-0101(02)00369-0","article-title":"Inhibition of brevetoxin binding to the voltage-gated sodium channel by gambierol and gambieric acid-A","volume":"41","author":"Inoue","year":"2003","journal-title":"Toxicon"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S0040-4039(00)86674-5","article-title":"Goniodomin A, a novel polyether macrolide from the dinoflagellate Goniodoma pseudogoniaulax","volume":"29","author":"Murakami","year":"1988","journal-title":"Tetrahedron Lett."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.hal.2005.08.004","article-title":"Production of goniodomin A by the planktonic, chain-forming dinoflagellate Alexandrium monilatum (Howell) Balech isolated from the Gulf Coast of the United States","volume":"5","author":"Hsia","year":"2006","journal-title":"Harmful Algae"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.toxicon.2015.12.018","article-title":"First report of goniodomin A production by the dinoflagellate Alexandrium pseudogonyaulax developing in southern Mediterranean (Bizerte Lagoon, Tunisia)","volume":"111","author":"Triki","year":"2016","journal-title":"Toxicon"},{"key":"ref_199","first-page":"10","article-title":"Cytotoxicity of goniodomin A and B in non contractile cells","volume":"250","author":"Cagide","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1248\/cpb.c16-00281","article-title":"Search for new bioactive marine natural products and application to drug development","volume":"64","author":"Kobayashi","year":"2016","journal-title":"Chem. Pharm. Bull."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.chembiol.2004.07.014","article-title":"Amphidinolide H, a potent cytotoxic macrolide, covalently binds on actin subdomain 4 and stabilizes actin filament","volume":"11","author":"Usui","year":"2004","journal-title":"Chem. Biol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/ja.2008.39","article-title":"Amphidinolides and its related macrolides from marine dinoflagellates","volume":"61","author":"Kobayashi","year":"2008","journal-title":"J. Antibiot."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.biotechadv.2006.11.008","article-title":"Biotechnological significance of toxic marine dinoflagellates","volume":"25","author":"Camacho","year":"2007","journal-title":"Biotechnol. Adv."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.hal.2004.07.004","article-title":"The structures of five new antifungal and hemolytic amphidinol analogs from Amphidinium carterae collected in New Zealand","volume":"4","author":"Echigoya","year":"2005","journal-title":"Harmful Algae"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1021\/np500275x","article-title":"Antifungal amphidinol 18 and its 7-sulfate derivative from the marine dinoflagellate Amphidinium carterae","volume":"77","author":"Nuzzo","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Cutignano, A., Nuzzo, G., Sardo, A., and Fontana, A. (2017). The Missing piece in biosynthesis of amphidinols: First evidence of glycolate as a starter unit in New Polyketides from Amphidinium Carterae. Mar. Drugs, 15.","DOI":"10.3390\/md15060157"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1021\/acs.jnatprod.7b00345","article-title":"Structures of the largest amphidinol homologues from the dinoflagellate Amphidinium carterae and structure\u2013activity relationships","volume":"80","author":"Satake","year":"2017","journal-title":"J. Nat. Prod."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"9859","DOI":"10.1021\/ja00026a027","article-title":"Amphidinol, a polyhydroxy-polyene antifungal agent with an unprecedented structure, from a marine dinoflagellate, Amphidinium Kleb","volume":"113","author":"Satake","year":"1991","journal-title":"J. Am. Chem. Soc."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/j.bmcl.2010.02.025","article-title":"Sterol effect on interaction between amphidinol 3 and liposomal membrane as evidenced by surface plasmon resonance","volume":"20","author":"Swasono","year":"2010","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1016\/j.tetlet.2014.04.086","article-title":"Amphirionin-5, a novel linear polyketide from a cultured marine dinoflagellate Amphidinium species with a potent cell proliferation-promoting activity","volume":"55","author":"Akakabe","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.1021\/ol5023504","article-title":"Amphirionin-4 with potent proliferation-promoting activity on bone marrow stromal cells from a marine dinoflagellate Amphidinium species","volume":"16","author":"Minamida","year":"2014","journal-title":"Org. Lett."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1016\/j.tet.2014.03.025","article-title":"Iriomoteolide-13a, a cytotoxic 22-membered macrolide from a marine dinoflagellate Amphidinium species","volume":"70","author":"Akakabe","year":"2014","journal-title":"Tetrahedron"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1007\/BF01959173","article-title":"Symbioramide, a novel Ca2+-ATPase activator from the cultured dinoflagellate Symbiodinium sp.","volume":"44","author":"Kobayashi","year":"1988","journal-title":"Experientia"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1021\/np50062a001","article-title":"Pharmacologically active metabolites from symbiotic microalgae in Okinawan marine invertebrates","volume":"52","author":"Kobayashi","year":"1989","journal-title":"J. Nat. Prod."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"5448","DOI":"10.1021\/jo00046a029","article-title":"Gambieric acids, new potent antifungal substances with unprecedented polyether structures from a marine dinoflagellate Gamb","volume":"57","author":"Nagai","year":"1992","journal-title":"Toxicus. J. Org. Chem."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/4\/271\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:56:14Z","timestamp":1760136974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/4\/271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,18]]},"references-count":215,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["md20040271"],"URL":"https:\/\/doi.org\/10.3390\/md20040271","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,18]]}}}