Jellyfish stings are the most common marine animal injuries worldwide, with approximately 150 million envenomation cases annually, and the victims may suffer from severe pain, itching, swelling, inflammation, arrhythmias, cardiac failure, or even death. Consequently, identification of effective first aid reagents for jellyfish envenoming is urgently needed. Here, we found that the polyphenol epigallocatechin-3-gallate (EGCG) markedly antagonized the hemolytic toxicity, proteolytic activity, and cardiomyocyte toxicity of the jellyfish Nemopilema nomurai venom in vitro and could prevent and treat systemic envenoming caused by N. nomurai venom in vivo. Moreover, EGCG is a natural plant active ingredient and widely used as a food additive without toxic side effects. Hence, we suppose that EGCG might be an effective antagonist against systemic envenoming induced by jellyfish venom.

Vibrio vulnificus (V. vulnificus) infection-associated multiple antibiotic resistance has raised serious public health concerns. Recently, nanosponges (NSs) have been expected to provide innovative platforms for addressing antibacterial and drug-resistant challenges by targeting various pore-forming toxins (PFTs). In the present study, we constructed NSs to explore the effects and possible mechanism of recombinant V. vulnificus hemolysin (rVvhA)-induced injuries. In vitro, NSs significantly reversed rVvhA-induced apoptosis and necrosis, and improved toxin-induced intracellular reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, and apoptosis signaling pathway disruption. To explore the clinical translation potential of NSs, we established VvhA-induced septicemia and wound infection mouse models, respectively, and further found NSs could notably attenuate rVvhA-induced acute toxicity and septicemia-associated inflammation, as well as local tissue damage. In a conclusion, NSs showed excellent protective effects against rVvhA-induced toxicity, thus providing useful insights into addressing the rising threats of severe V. vulnificus infections.

Tetrodotoxin (TTX) is a highly fatal marine biotoxin. Constantly increasing intoxications and the lack of specific antitoxic drugs in clinical applications highlight the need for further research into the toxic effects of TTX. Current reports on poisoning cases and the TTX toxicity mechanism suggest that the blocking of voltage-gated sodium channels (VGSCs) by TTX is probably reversible, but direct evidence of this is lacking, as far as we are aware. This study explored the acute toxic effects of TTX at sub-lethal doses via different routes, analyzing variations in muscle strength and TTX concentration in the blood in mice. We found that the loss of muscle strength in mice caused by TTX was dose-dependent and reversible, and the death time and muscle strength variations after oral gavage with TTX appeared to occur later and were more variable than those after intramuscular injection. In conclusion, we systematically compared the acute toxic effects of TTX for two different administration routes at sub-lethal doses, directly verifying the reversible reaction of TTX blocking VGSCs and speculating that averting a complete block of VGSCs by TTX could be an effective strategy for preventing death from TTX poisoning. This work may provide data for the diagnosis and treatment of TTX poisoning.

Nemopilema nomurai is a species of common large toxic jellyfish in China seas, and its tentacle tissues contain various types of nematocysts. However, the correlation between the morphology and function of nematocysts still remains unclear. In this study, we first obtained two monomorphic nematocysts with high-purity from N. nomurai, namely Anisorhizas and O-isorhizas, by density gradient centrifugation: the Anisorhizas is small and rod-shaped and the O-isorhizas is larger and spherical. Upon deionized water stimulation, O-isorhizas exhibited a stronger discharge capability than Anisorhizas. The nematocyst contents of Anisorhizas (AnC) and O-isorhizas (OnC) were extracted separately, and their composition and bioactivities were analyzed simultaneously. The protein bands by SDS-PAGE revealed similar distributions in AnC and OnC, except that the protein band distribution in OnC was more extensive. OnC showed stronger cytotoxicity, hemolytic activity, metalloprotease activity, and serine protease activity than AnC. In contrast, AnC exhibited a higher antioxidant activity and significant proinflammatory activity. Both AnC and OnC exhibited antimicrobial activities against certain marine pathogenic Vibrios. These results suggest that O-isorhizas, with the larger capsule capability, stronger discharge ability and toxicity, likely plays a major role in inducing toxic effects and tissue damage, while Anisorhizas, being smaller and less toxic, may undertake preferentially other functions, such as synergistic predation, environmental stress adaptation, and energy balance maintenance. This study provides insights into the morpho-functional relationship between various types of nematocysts, and also lays a foundation for further exploration of the functional diversity of nematocysts and the mechanisms underlying jellyfish envenomation.

Nemopilema nomurai is a species of common large toxic jellyfish in China seas, and its tentacle tissues contain various types of nematocysts. However, the correlation between the morphology and function of nematocysts still remains unclear. In this study, we first obtained two monomorphic nematocysts with high-purity from N. nomurai, namely Anisorhizas and O-isorhizas, by density gradient centrifugation: the Anisorhizas is small and rod-shaped and the O-isorhizas is larger and spherical. Upon deionized water stimulation, O-isorhizas exhibited a stronger discharge capability than Anisorhizas. The nematocyst contents of Anisorhizas (AnC) and O-isorhizas (OnC) were extracted separately, and their composition and bioactivities were analyzed simultaneously. The protein bands by SDS-PAGE revealed similar distributions in AnC and OnC, except that the protein band distribution in OnC was more extensive. OnC showed stronger cytotoxicity, hemolytic activity, metalloprotease activity, and serine protease activity than AnC. In contrast, AnC exhibited a higher antioxidant activity and significant proinflammatory activity. Both AnC and OnC exhibited antimicrobial activities against certain marine pathogenic Vibrios. These results suggest that O-isorhizas, with the larger capsule capability, stronger discharge ability and toxicity, likely plays a major role in inducing toxic effects and tissue damage, while Anisorhizas, being smaller and less toxic, may undertake preferentially other functions, such as synergistic predation, environmental stress adaptation, and energy balance maintenance. This study provides insights into the morpho-functional relationship between various types of nematocysts, and also lays a foundation for further exploration of the functional diversity of nematocysts and the mechanisms underlying jellyfish envenomation.