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Keywords = Chironex fleckeri

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23 pages, 3183 KB  
Review
Jellyfish Venom-Induced Cardiotoxicity and Immune Responses: Mechanisms and Potential Therapeutic Strategies
by Yueyue Li, Zhiwen Qiu, Bingbing Li, Xiaoyu Geng, Xuelu Yu, Yue Li, Wei Li and Jishun Yang
Mar. Drugs 2025, 23(10), 369; https://doi.org/10.3390/md23100369 - 23 Sep 2025
Cited by 1 | Viewed by 4510
Abstract
Jellyfish stings represent a significant global marine hazard, causing injuries from localized skin damage to fatal systemic complications. While skin reactions are the most common symptom, heart toxicity (cardiotoxicity) is the primary cause of death. A growing body of evidence shows that the [...] Read more.
Jellyfish stings represent a significant global marine hazard, causing injuries from localized skin damage to fatal systemic complications. While skin reactions are the most common symptom, heart toxicity (cardiotoxicity) is the primary cause of death. A growing body of evidence shows that the immune system’s response worsens this venom-induced heart damage. However, current research remains disproportionately focused on cutaneous inflammatory responses, leaving systemic immunopathological processes—especially those potentiating cardiotoxicity—poorly understood. Moreover, few jellyfish toxins (like those from the Chironex fleckeri) have been thoroughly studied, and the molecular mechanisms of heart injury remain largely unknown. This review introduces a novel pathophysiological classification of jellyfish envenomation into three distinct categories—immunotoxicity-dominant, cardiotoxicity-dominant, and dual-mechanism synergistic—based on clinical and mechanistic profiles. By synthesizing current knowledge on venom components and their multi-system interaction, we aim to identify actionable therapeutic targets and propose mechanism-driven treatment strategies. This refined classification offers a foundation for future clinical decision-making and the development of targeted therapies, potentially improving patient outcomes through more personalized envenomation management. Full article
(This article belongs to the Special Issue Jellyfish-Derived Compounds)
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31 pages, 9469 KB  
Article
Elucidation of Medusozoan (Jellyfish) Venom Constituent Activities Using Constellation Pharmacology
by Angel A. Yanagihara, Matías L. Giglio, Kikiana Hurwitz, Raechel Kadler, Samuel S. Espino, Shrinivasan Raghuraman and Baldomero M. Olivera
Toxins 2024, 16(10), 447; https://doi.org/10.3390/toxins16100447 - 17 Oct 2024
Cited by 4 | Viewed by 3493
Abstract
Within the phylum Cnidaria, sea anemones (class Anthozoa) express a rich diversity of ion-channel peptide modulators with biomedical applications, but corollary discoveries from jellyfish (subphylum Medusozoa) are lacking. To bridge this gap, bioactivities of previously unexplored proteinaceous and small molecular weight (~15 kDa [...] Read more.
Within the phylum Cnidaria, sea anemones (class Anthozoa) express a rich diversity of ion-channel peptide modulators with biomedical applications, but corollary discoveries from jellyfish (subphylum Medusozoa) are lacking. To bridge this gap, bioactivities of previously unexplored proteinaceous and small molecular weight (~15 kDa to 5 kDa) venom components were assessed in a mouse dorsal root ganglia (DRG) high-content calcium-imaging assay, known as constellation pharmacology. While the addition of crude venom led to nonspecific cell death and Fura-2 signal leakage due to pore-forming activity, purified small molecular weight fractions of venom demonstrated three main, concentration-dependent and reversible effects on defined heterogeneous cell types found in the primary cultures of mouse DRG. These three phenotypic responses are herein referred to as phenotype A, B and C: excitatory amplification (A) or inhibition (B) of KCl-induced calcium signals, and test compound-induced disturbances to baseline calcium levels (C). Most notably, certain Alatina alata venom fractions showed phenotype A effects in all DRG neurons; Physalia physalis and Chironex fleckeri fractions predominantly showed phenotype B effects in small- and medium-diameter neurons. Finally, specific Physalia physalis and Alatina alata venom components induced direct excitatory responses (phenotype C) in glial cells. These findings demonstrate a diversity of neuroactive compounds in jellyfish venom potentially targeting a constellation of ion channels and ligand-gated receptors with broad physiological implications. Full article
(This article belongs to the Section Animal Venoms)
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15 pages, 2093 KB  
Article
Use of eDNA to Determine Source Locations of Deadly Jellyfish (Cubozoa) in an Open Coastal System
by Scott J. Morrissey, Dean R. Jerry and Michael J. Kingsford
Coasts 2024, 4(1), 198-212; https://doi.org/10.3390/coasts4010011 - 5 Mar 2024
Cited by 7 | Viewed by 3309
Abstract
Challenges associated with cubozoan jellyfish detection and the limitations of current detection techniques limit the ability of scientists to fill critical knowledge gaps surrounding their ecology. Environmental DNA (eDNA), however, has proven useful as an ecological survey tool to detect and study these [...] Read more.
Challenges associated with cubozoan jellyfish detection and the limitations of current detection techniques limit the ability of scientists to fill critical knowledge gaps surrounding their ecology. Environmental DNA (eDNA), however, has proven useful as an ecological survey tool to detect and study these deadly jellyfish. This study aimed to leverage the power of eDNA to detect and explore the distribution of the Australian box jellyfish (Chironex fleckeri), encompassing both its medusae and polyp life history stages, within an open coastal bay (Horseshoe Bay) of Magnetic Island, Queensland, Australia. Our investigation focused on a hypothesis concerning the source locations of the jellyfish within Horseshoe Bay and, through a comparison of both life history stage distributions, aimed to determine potential population stock boundaries. eDNA results aligned with the predicted nearshore distribution of medusae. Further, the elusive benthic polyp stage was also detected. These findings confirmed Horseshoe Bay as a source location of the jellyfish. Moreover, our evidence supported a model that the area likely represents a population stock of the species. This adds to growing evidence suggesting some cubozoan jellyfish have population stocks of small spatial scales in both open and relatively closed ecosystems such as estuaries. In conclusion, this study serves as a notable example of eDNA’s ability to resolve critical knowledge gaps surrounding cubozoan ecology and to enhance the management ability of these deadly jellyfish to reduce envenomations. Full article
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27 pages, 2261 KB  
Review
Investigation of Best Practices for Venom Toxin Purification in Jellyfish towards Functional Characterisation
by Blake Lausen, Anahita Ahang, Scott Cummins and Tianfang Wang
Toxins 2023, 15(3), 170; https://doi.org/10.3390/toxins15030170 - 21 Feb 2023
Cited by 5 | Viewed by 6075
Abstract
The relative lack of marine venom pharmaceuticals can be anecdotally attributed to difficulties in working with venomous marine animals, including how to maintain venom bioactivity during extraction and purification. The primary aim of this systematic literature review was to examine the key factors [...] Read more.
The relative lack of marine venom pharmaceuticals can be anecdotally attributed to difficulties in working with venomous marine animals, including how to maintain venom bioactivity during extraction and purification. The primary aim of this systematic literature review was to examine the key factors for consideration when extracting and purifying jellyfish venom toxins to maximise their effectiveness in bioassays towards the characterisation of a single toxin.An up-to-date database of 119 peer-reviewed research articles was established for all purified and semi-purified venoms across all jellyfish, including their level of purification, LD50, and the types of experimental toxicity bioassay used (e.g., whole animal and cell lines). We report that, of the toxins successfully purified across all jellyfish, the class Cubozoa (i.e., Chironex fleckeri and Carybdea rastoni) was most highly represented, followed by Scyphozoa and Hydrozoa. We outline the best practices for maintaining jellyfish venom bioactivity, including strict thermal management, using the “autolysis” extraction method and two-step liquid chromatography purification involving size exclusion chromatography. To date, the box jellyfish C. fleckeri has been the most effective jellyfish venom model with the most referenced extraction methods and the most isolated toxins, including CfTX-A/B. In summary, this review can be used as a resource for the efficient extraction, purification, and identification of jellyfish venom toxins. Full article
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20 pages, 2349 KB  
Article
Genetic Detection and a Method to Study the Ecology of Deadly Cubozoan Jellyfish
by Scott J. Morrissey, Dean R. Jerry and Michael J. Kingsford
Diversity 2022, 14(12), 1139; https://doi.org/10.3390/d14121139 - 19 Dec 2022
Cited by 13 | Viewed by 4665
Abstract
Cubozoan jellyfish pose a risk of envenomation to humans and a threat to many businesses, yet crucial gaps exist in determining threats to stakeholders and understanding their ecology. Environmental DNA (eDNA) provides a cost-effective method for detection that is less labour intensive and [...] Read more.
Cubozoan jellyfish pose a risk of envenomation to humans and a threat to many businesses, yet crucial gaps exist in determining threats to stakeholders and understanding their ecology. Environmental DNA (eDNA) provides a cost-effective method for detection that is less labour intensive and provides a higher probability of detection. The objective of this study was to develop, optimise and trial the use of eDNA to detect the Australian box jellyfish, Chironex fleckeri. This species was the focus of this study as it is known to have the strongest venom of any cubozoan; it is responsible for more than 200 recorded deaths in the Indo-Pacific region. Further, its ecology is poorly known. Herein, a specific and sensitive probe-based assay, multiplexed with an endogenous control assay, was developed, and successfully utilised to detect the deadly jellyfish species and differentiate them from closely related taxa. A rapid eDNA decay rate of greater than 99% within 27 h was found with no detectable influence from temperature. The robustness of the technique indicates that it will be of high utility for detection and to address knowledge gaps in the ecology of C. fleckeri; further, it has broad applicability to other types of zooplankton. Full article
(This article belongs to the Special Issue Advances in the Diversity and Ecology of Zooplankton)
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27 pages, 13401 KB  
Review
Raising Awareness on the Clinical and Forensic Aspects of Jellyfish Stings: A Worldwide Increasing Threat
by Sara Almeida Cunha and Ricardo Jorge Dinis-Oliveira
Int. J. Environ. Res. Public Health 2022, 19(14), 8430; https://doi.org/10.3390/ijerph19148430 - 10 Jul 2022
Cited by 31 | Viewed by 22352
Abstract
Jellyfish are ubiquitous animals registering a high and increasing number of contacts with humans in coastal areas. These encounters result in a multitude of symptoms, ranging from mild erythema to death. This work aims to review the state-of-the-art regarding pathophysiology, diagnosis, treatment, and [...] Read more.
Jellyfish are ubiquitous animals registering a high and increasing number of contacts with humans in coastal areas. These encounters result in a multitude of symptoms, ranging from mild erythema to death. This work aims to review the state-of-the-art regarding pathophysiology, diagnosis, treatment, and relevant clinical and forensic aspects of jellyfish stings. There are three major classes of jellyfish, causing various clinical scenarios. Most envenomations result in an erythematous lesion with morphological characteristics that may help identify the class of jellyfish responsible. In rare cases, the sting may result in delayed, persistent, or systemic symptoms. Lethal encounters have been described, but most of those cases happened in the Indo-Pacific region, where cubozoans, the deadliest jellyfish class, can be found. The diagnosis is mostly clinical but can be aided by dermoscopy, skin scrapings/sticky tape, confocal reflectance microscopy, immunological essays, among others. Treatment is currently based on preventing further envenomation, inactivating the venom, and alleviating local and systemic symptoms. However, the strategy used to achieve these effects remains under debate. Only one antivenom is currently used and covers merely one species (Chironex fleckeri). Other antivenoms have been produced experimentally but were not tested on human envenomation settings. The increased number of cases, especially due to climate changes, justifies further research in the study of clinical aspects of jellyfish envenoming. Full article
(This article belongs to the Special Issue Climate Change and Environment Health)
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12 pages, 2631 KB  
Article
Structural Characterisation of Predicted Helical Regions in the Chironex fleckeri CfTX-1 Toxin
by Athena Andreosso, Paramjit S. Bansal, Michael J. Smout, David Wilson, Jamie E. Seymour and Norelle L. Daly
Mar. Drugs 2018, 16(6), 201; https://doi.org/10.3390/md16060201 - 7 Jun 2018
Cited by 10 | Viewed by 7491
Abstract
The Australian jellyfish Chironex fleckeri, belongs to a family of cubozoan jellyfish known for their potent venoms. CfTX-1 and -2 are two highly abundant toxins in the venom, but there is no structural data available for these proteins. Structural information on toxins [...] Read more.
The Australian jellyfish Chironex fleckeri, belongs to a family of cubozoan jellyfish known for their potent venoms. CfTX-1 and -2 are two highly abundant toxins in the venom, but there is no structural data available for these proteins. Structural information on toxins is integral to the understanding of the mechanism of these toxins and the development of an effective treatment. Two regions of CfTX-1 have been predicted to have helical structures that are involved with the mechanism of action. Here we have synthesized peptides corresponding to these regions and analyzed their structures using NMR spectroscopy. The peptide corresponding to the predicted N-terminal amphiphilic helix appears unstructured in aqueous solution. This lack of structure concurs with structural disorder predicted for this region of the protein using the Protein DisOrder prediction System PrDOS. Conversely, a peptide corresponding to a predicted transmembrane region is very hydrophobic, insoluble in aqueous solution and predicted to be structured by PrDOS. In the presence of SDS-micelles both peptides have well-defined helical structures showing that a membrane mimicking environment stabilizes the structures of both peptides and supports the prediction of the transmembrane region in CfTX-1. This is the first study to experimentally analyze the structure of regions of a C. fleckeri protein. Full article
(This article belongs to the Special Issue Marine Invertebrate Toxins)
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15 pages, 2217 KB  
Article
Cubozoan Sting-Site Seawater Rinse, Scraping, and Ice Can Increase Venom Load: Upending Current First Aid Recommendations
by Angel Anne Yanagihara and Christie L. Wilcox
Toxins 2017, 9(3), 105; https://doi.org/10.3390/toxins9030105 - 15 Mar 2017
Cited by 30 | Viewed by 44274
Abstract
Cnidarian envenomations are the leading cause of severe and lethal human sting injuries from marine life. The total amount of venom discharged into sting-site tissues, sometimes referred to as “venom load”, has been previously shown to correlate with tentacle contact length and sequelae [...] Read more.
Cnidarian envenomations are the leading cause of severe and lethal human sting injuries from marine life. The total amount of venom discharged into sting-site tissues, sometimes referred to as “venom load”, has been previously shown to correlate with tentacle contact length and sequelae severity. Since <1% of cnidae discharge upon initial tentacle contact, effective and safe removal of adherent tentacles is of paramount importance in the management of life-threatening cubozoan stings. We evaluated whether common rinse solutions or scraping increased venom load as measured in a direct functional assay of venom activity (hemolysis). Scraping significantly increased hemolysis by increasing cnidae discharge. For Alatina alata, increases did not occur if the tentacles were first doused with vinegar or if heat was applied. However, in Chironex fleckeri, vinegar dousing and heat treatment were less effective, and the best outcomes occurred with the use of venom-inhibiting technologies (Sting No More® products). Seawater rinsing, considered a “no-harm” alternative, significantly increased venom load. The application of ice severely exacerbated A. alata stings, but had a less pronounced effect on C. fleckeri stings, while heat application markedly reduced hemolysis for both species. Our results do not support scraping or seawater rinsing to remove adherent tentacles. Full article
(This article belongs to the Section Animal Venoms)
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15 pages, 1718 KB  
Article
Firing the Sting: Chemically Induced Discharge of Cnidae Reveals Novel Proteins and Peptides from Box Jellyfish (Chironex fleckeri) Venom
by Mahdokht Jouiaei, Nicholas R. Casewell, Angel A. Yanagihara, Amanda Nouwens, Bronwen W. Cribb, Darryl Whitehead, Timothy N. W. Jackson, Syed A. Ali, Simon C. Wagstaff, Ivan Koludarov, Paul Alewood, Jay Hansen and Bryan G. Fry
Toxins 2015, 7(3), 936-950; https://doi.org/10.3390/toxins7030936 - 18 Mar 2015
Cited by 58 | Viewed by 17725
Abstract
Cnidarian venom research has lagged behind other toxinological fields due to technical difficulties in recovery of the complex venom from the microscopic nematocysts. Here we report a newly developed rapid, repeatable and cost effective technique of venom preparation, using ethanol to induce nematocyst [...] Read more.
Cnidarian venom research has lagged behind other toxinological fields due to technical difficulties in recovery of the complex venom from the microscopic nematocysts. Here we report a newly developed rapid, repeatable and cost effective technique of venom preparation, using ethanol to induce nematocyst discharge and to recover venom contents in one step. Our model species was the Australian box jellyfish (Chironex fleckeri), which has a notable impact on public health. By utilizing scanning electron microscopy and light microscopy, we examined nematocyst external morphology before and after ethanol treatment and verified nematocyst discharge. Further, to investigate nematocyst content or “venom” recovery, we utilized both top-down and bottom-up transcriptomics–proteomics approaches and compared the proteome profile of this new ethanol recovery based method to a previously reported high activity and recovery protocol, based upon density purified intact cnidae and pressure induced disruption. In addition to recovering previously characterized box jellyfish toxins, including CfTX-A/B and CfTX-1, we recovered putative metalloproteases and novel expression of a small serine protease inhibitor. This study not only reveals a much more complex toxin profile of Australian box jellyfish venom but also suggests that ethanol extraction method could augment future cnidarian venom proteomics research efforts. Full article
(This article belongs to the Special Issue Selected Papers from the 5th Venoms to Drugs Meeting)
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