Rational attenuation of elapid long-chain neurotoxin by targeted residue substitution and disulfide architecture simplification: implications for receptor interaction and immune recognition

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  Rational attenuation of elapid long-chain neurotoxin by targeted residue substitution and disulfide architecture simplification: implications for receptor interaction and immune recognition Abstract Elapid long-chain neurotoxins (LNTxs) exert their toxicity through high-affinity binding to nicotinic acetylcholine receptors (nAChRs). Specific residues mediate this process, including basic (Lys23, Arg33, Arg36, Lys49), structural (Cys26, Cys30), and aromatic (Phe29) amino acids. To investigate the functional and immunogenic implications of modifying these residues, we designed two recombinant variants of a consensus LNTx. The first variant, rLcNTx V1, contains charge-reversal mutations at four key basic positions, while the second, rLcNTx V2, lacks the segment corresponding to the fifth disulfide bond. We expressed both variants in Escherichia coli Origami cells. rLcNTx V1 was recovered in a soluble form, but rLcNTx V2 was present only in inclusion bodies. We assessed the binding ...

From sting to STING: role of inflammation in wasp sting induced AKI - a narrative review

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From sting to STING: role of inflammation in wasp sting induced AKI - a narrative review

Abstract

Multiple wasp stings that induce acute kidney injury (AKI) pose a significant threat to human health. This review focuses on the roles and mechanisms of inflammation in wasp sting-induced AKI. Relevant clinical studies, although limited in scope, have reported elevated levels of various inflammatory mediators in patients. These increased inflammatory mediators serve as indicators of inflammation and are potential predictors of wasp sting-induced AKI. However, clinical research is impeded by factors such as inconsistent patient baselines and lack of standardization for the use of wasp venom. To further explore the mechanisms, animal and cellular models have been developed to mimic the clinical manifestations. Basic studies have confirmed that inflammation plays a crucial role in such injuries. Importantly, mitochondrial DNA release and the cyclic GMP-AMP synthase-stimulator of interferon genes (STING) signaling axis have been identified as key regulators of the inflammatory response in wasp sting-induced AKI. These studies on inflammation present potential targets for therapeutic interventions, and plasma exchange has been proven effective. Overall, this review provides in-depth insights into the mechanisms and basis of therapeutic strategies for the treatment of wasp sting-induced AKI pathogenesis.


Xu, L., Zhou, Z., Lv, Y. et al. From sting to STING: role of inflammation in wasp sting induced AKI - a narrative review. BMC Nephrol 26, 471 (2025). https://doi.org/10.1186/s12882-025-04403-w