The chromosome-level genome of Mesobuthus martensii provides insights into its evolution and the diversity of venom peptides

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  The chromosome-level genome of Mesobuthus martensii provides insights into its evolution and the diversity of venom peptides Abstract Mesobuthus martensii , the source species of the traditional Chinese medicine “Quanxie”, has long been utilized for its therapeutic properties. Venom peptides are recognized as the major active molecular basis of these pharmacological activities. Despite this, their development as therapeutic agents remains poorly explored. In this study, we performed an integrated multi-omics investigation to systematically explore the venom peptides of Mesobuthus martensii . We generated a chromosome-level genome assembly of Mesobuthus martensii using third-generation sequencing technologies, yielding a genome size of 1.08 Gb with a contig N50 of 46.46 Mb. Integrated genomic and transcriptomic analyses led to the identification of 51 putative novel venom peptide candidates. From the broader venom peptide set, five lysine- and arginine-rich candidates were select...

Modulation of Skin Inflammation by a Recombinant Brown Spider Venom Phospholipase D: In Silico and In Vitro Approaches

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Modulation of Skin Inflammation by a Recombinant Brown Spider Venom Phospholipase D: In Silico and In Vitro Approaches

Abstract

Envenomation by Loxosceles spiders produces a condition termed loxoscelism, which may manifest in cutaneous and systemic forms. Cutaneous loxoscelism is characterized by intense inflammation and dermonecrosis, driven mainly by phospholipase D (PLD) toxins in Loxosceles venom. This study investigated the molecular mechanisms and cellular contributions underlying these effects. Human dermal and epidermal cells, including keratinocytes, fibroblasts, and endothelial cells, were used. Recombinant PLD from L. intermedia venom, LiRecDT1, was employed as the toxin model. Functional assays evaluated leukocyte adhesion to endothelial cells exposed to LiRecDT1 and toxin-treated media from keratinocytes and fibroblasts. Further analysis explored a systems biology approach to model cellular signaling networks activated by PLDs. Finally, the cells were exposed to LiRecDT1, and gene expression was quantified via RT-qPCR to assess cellular responses. LiRecDT1 and conditioned media from treated keratinocytes and fibroblasts promoted leukocyte adhesion to endothelial cells. Based on in silico predictions, key pathway nodes were identified and validated experimentally. The increased expression of inflammatory mediators IL-1β, IL-6 and cellular stress TNF-α genes in all cells peaked at 4 hours, consistent with a pattern of acute inflammation. Cell-type-specific differences became apparent by 24 h in the distinct modulation of STAT3, IL1β, TNF-α and AKT1, as well as in the unexplored targets RELA, TP53, STAT3, and c-JUN. Prolonged exposition to the toxin demonstrated modulation of some of these pathways related to chronic/unresolved inflammation, immune modulation and fibrotic remodeling. These findings highlight the coordinated contributions of skin-resident cells to cutaneous loxoscelism and highlight novel potential targets for therapeutic intervention.
Schluga, P. H. D. C., Boia-Ferreira, M., Theodoro, J. L., De Fraga-Ferreira, M. E., Schemczssen-Graeff, Z., Senff-Ribeiro, A., Vargas, J. E., Sanches Veiga, S., & Gremski, L. H. (2026). Modulation of Skin Inflammation by a Recombinant Brown Spider Venom Phospholipase D: In Silico and In Vitro Approaches. Advances in Biological Regulation, 101160. https://doi.org/10.1016/j.jbior.2026.101160