Search Results (2,152)

The use of Steinernema carpocapsae infective juveniles as biological control agents is a long-standing practice, yet the oral impact of their secreted venom proteins on crop pests remains largely unknown. We evaluated the oral toxicity of S. carpocapsae venom proteins against Spodoptera frugiperda using artificial diet assays. Ingestion caused significant dose-dependent toxicity in early-instar larvae, resulting in mortality and a prolonged developmental duration. Carry-over effects were profound; treated pupae were smaller and malformed, with only 19% of larvae fed on 1000 ng g⁻¹ venom protein-supplemented diet reaching adulthood compared to 92% in controls. Surviving adults lived 30% fewer days and laid over 90% fewer morphologically normal eggs. These physiological disruptions coincided with elevated oxidative stress and detoxification enzyme activity, suggesting the venom induces oxidative and detoxification responses, which may be associated with the observed phenotypic alterations. This study provides the first demonstration of the oral toxicity of entomopathogenic nematode venom proteins, positioning them as a promising resource for the discovery of novel insecticidal proteins for sustainable pest management. Full article

Scorpion neurotoxins are small peptides that target ion channels and offer opportunities for novel therapeutic discovery. This study analyzed the functional effects of the venom and toxins from the Costa Rican endemic scorpion, Tityus championi. Initially, crude venom was tested on different isoforms of voltage-gated sodium channels. Our findings revealed that the venom contains toxins that affect mammalian Na_V1.6 and Na_V1.7, as well as the cockroach BgNa_V1 channel. Increased currents through Na_V1.6 and BgNa_V1 channels were associated with bigger window currents and inhibition of inactivation. Decreased Na_V1.7 currents were associated with smaller conductance. Crude venom and TCh3 toxin inhibited action potential generation in invertebrate neurons expressing Na_V1.7-like channels. In these neurons, Tch2 and Tch4 toxins shifted voltage sensitivity to more negative potentials, ultimately widening the window current but decreasing channel availability. Conversely, Tch3 behaved as an inhibitory toxin, closing window currents and decreasing channel availability. Structural modeling showed that Tch3 adopts an αββ fold and binds the S3–S4 loop of Domain II in human Na_V1.7. These data show the diverse effects of scorpion venoms on channels and neurons, characterize its principal toxins, and show that Tch3 has therapeutic potential for pain relief. Full article

Background: Accidents caused by the Loxosceles laeta spider constitute a health problem in South America. Envenomation can lead to severe systemic manifestations, eventually compromising the patient’s life. Most regional health authorities consider antivenom administration the basis of effective treatment in the most serious cases. The availability of spider venom is the primary bottleneck for antivenom production. Herein, we present a novel biotechnological approach, based on the expression of recombinant versions of the most relevant toxin in loxoscelism, sphingomyelinase D (SphD), in insect larvae (Spodoptera frugiperda). Methods: We produced two versions of SphD: one conserving its biological activities (wtSphD) and a second alternative that was designed to be genetically detoxified (dSphD). Two horses were subjected to three consecutive hyperimmunization cycles with dSphD. The horses’ plasma was extracted at the end of each cycle and used to produce Active Pharmaceutical Ingredients (APIs) of antivenoms at a pilot scale. Results: Dermonecrotic activity of wtSphD was completely neutralized with the sera obtained from one horse and partially with that of the other. In contrast, the APIs derived in both cases completely neutralized wtSphD dermonecrotic activity. Direct hemolysis of human red blood cells by wtSphD was also neutralized by sera and APIs. Conclusions: These results show venom replacement or complementation potential by recombinant dSphD produced in this novel platform. Full article

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the cellular antioxidant response and a promising therapeutic target for Parkinson’s disease (PD). Resibufogenin (RBG), a bioactive bufadienolide from toad venom, has been identified as a potential Nrf2 agonist; however, its application is limited by cytotoxicity and poor drug-like properties. Herein, we report the rational design, synthesis, and biological evaluation of a series of RBG derivatives modified at the C3, C14–C15, and C17 positions. Systematic structure–activity relationship (SAR) studies identified 2-5c, featuring a C3 2-chloroacryloyl group and a C17 pyrimidine substitution, as a potential Nrf2 activator (EC₅₀ = 4.18 μM), exhibiting approximately 7-fold greater activity than RBG. Importantly, 2-5c demonstrated neuroprotective effects in MPP⁺-induced BV2 microglial cells and effectively ameliorated motor deficits in an MPTP-induced PD mouse model. These findings suggest that 2-5c represents a promising candidate for further investigation in the development of novel Nrf2-based therapies for PD. Full article

In Croatia, the European Viper Venom Antiserum^®, produced by the Institute of Immunology Zagreb, was the only antiserum used to treat Vipera ammodytes envenomation. When production of the Zagreb antivenom ceased, three other antivenoms, Viperfav^®, BulBio^®, and Viekvin^®, replaced it in clinical practice at the Department of Infectious Diseases, University Hospital Split. This study includes 34 patients envenomed by Vipera ammodytes during the period between 2020 and 2025: 24 (71%) suffered grade 2a envenomation, nine (26%) grade 2b, and one grade 3 (severe envenomation). None were admitted to the Intensive Care Unit. All patients received antivenom: 16 received Viperfav^®, 17 BulBio^®, and one Viekvin^®. All grade 2a patients were treated with a single dose of antivenom. Among grade 2b patients, four received one dose and two received two doses of Viperfav^®, while one received one dose and two received two doses of BulBio^®. The grade 3 patient received two doses of BulBio^®. In all cases, treatment was successful and patients were discharged from hospital after an average of 3.97 days. Patients with pronounced neurotoxic signs did not require treatment with multiple doses of antivenom. All antivenoms proved effective. No adverse reactions or fatalities were observed. Full article

Neurotoxicity caused by snake venom phospholipase A₂ (PLA₂) activity derived from coral snakes (e.g., Micrurus tener, Micrurus fulvius, group IA PLA₂) and some rattlesnakes (e.g., Crotalus scutulatus, group IIA PLA₂) is medically significant. Of interest, the catalytic site of PLA₂ also binds to activated clotting factor X, causing anticoagulation. Given that ruthenium (Ru)-containing compounds have been demonstrated to inactivate hemotoxic venoms in a solvent-dependent manner (e.g., 0.9% NaCl, phosphate-buffered saline), we wished to determine if RuCl₃ would cause solvent-dependent inhibition of snake venom group IA and group IIA PLA₂ in human plasma with thrombelastography. It was determined that RuCl₃ significantly decreased the anticoagulant effects of group IA PLA₂ derived from M. tener and M. fulvius venoms in the presence of 0.9% NaCl, but not phosphate-buffered saline. In contrast, group IIA PLA₂ anticoagulant activity derived from C. scutulatus venom was inhibited by RuCl₃ in both solvents. It is concluded that the different ions formed by RuCl₃ in different solvents may interact with novel disulfide bridges unique to group IA and IIA PLA₂ or through some other mechanism. In vivo validation of Ru-based enzyme inhibitor effects on neurotoxicity associated with either group IA or IIA remains a critical translational issue. Full article

Background/Objectives: Hereditary alpha-tryptasemia (HαT) is increasingly recognized as a genetic modifier of mast cell-mediated disease severity and has been associated with heightened mediator-related symptoms and an elevated risk of anaphylaxis. This study aimed to describe the clinical characteristics, multisystem manifestations, and treatment responses of eight patients with HαT and concomitant mast cell disorders. Methods: In this single-center retrospective study, eight adults with confirmed TPSAB1 copy number gain and a diagnosis of systemic mastocytosis (SM), cutaneous mastocytosis (CM), or mast cell activation syndrome (MCAS) were evaluated. Baseline assessments included demographics, clinical history, basal serum tryptase (BST), TPSAB1 genotyping, KIT D816V testing, and bone marrow examination when indicated. Symptom burden was quantified at baseline and week 8 using the Mastocytosis Activity Score (MAS). All patients received mediator-targeted therapy; omalizumab was administered in selected high-risk cases. Results: Eight patients (62.5% male, mean age 53.9 ± 12.0 years) carried TPSAB1 duplication. The median BST was 16.2 ng/mL (range, 14.3–51.2). Severe anaphylaxis occurred in 75% of patients, predominantly drug-induced, while Hymenoptera venom triggered the remaining cases. Gastroesophageal reflux (87.5%), cutaneous symptoms (62.5%), neuropsychiatric features (62.5%), and autonomic dysfunction (37.5%) were common. The mean MAS decreased significantly from 27.25 ± 7.40 to 18.25 ± 6.48 after 8 weeks of high-dose antihistamines, with omalizumab providing marked additional benefit in selected patients. Conclusions: In this cohort, patients with HαT and coexisting mast cell disorders exhibited a high burden of mediator-related symptoms and a notable frequency of anaphylaxis. TPSAB1 genotyping may provide additional genetic information that aids in contextualizing clinical heterogeneity and mediator-related symptom burden in patients with mast cell disorders. Incorporation of HαT testing into routine evaluation may optimize individualized management. Full article

Rhabdophis lateralis is a snake species within the family Natricidae, which is widely distributed across mainland China, Russia, and Korea. Although this species was once thought to be non-venomous, there are quite a few cases demonstrating its bite could be fatal. In this study, we performed de novo assembly and analysis of the transcriptome data from the Duvernoy’s gland of R. lateralis, aiming to characterize its venom transcriptome and reveal the molecular basis of its toxicity. Among 6196 annotated transcripts, 77 were identified as potential toxin transcripts belonging to 26 toxin families. The most highly expressed toxin family was the SVMP family, accounting for 51.10% of the total toxin expression. The other notable toxins included cysteine-rich secretory proteins (CRISPs, 22.36%), c-type lectins (CTLs and snaclecs, 12.13%), and three-finger toxins (3Ftxs, 6.36%). Phylogenetic analyses indicated that SVMPs, CRISPs, and three-finger toxins (3FTxs) are evolutionarily conserved within Colubridae, whereas CTLs likely arose through convergent evolution. All identified SVMPs were classified as P-III type, with one sequence displaying a unique deletion distinct from conventional truncation patterns. The predominantly expressed CTLs are more likely to combine into dimers, exerting coagulation activity. This study provides an insight into the toxin gene expression in the Duvernoy’s gland of R. lateralis, which will benefit future research into the ecological and pharmacological significance of toxins in the genus Rhabdophis. Full article

Jellyfish, as representatives of the phylum Cnidaria, possess venoms characterized by structurally diverse and functionally complex toxins, rendering them a central focus in cnidarian toxin research. This article presents a systematic review of the physicochemical properties of jellyfish toxins, examines their mechanisms of action from a molecular biology perspective, investigates the patterns of toxin transformation in organisms, elucidates the structure–activity relationships between structure and toxicity, introduces advancements in research on novel jellyfish toxins, and offers an outlook on future developments in this field. By integrating modern proteomic techniques, such as liquid chromatography-tandem mass spectrometry, this review provides comprehensive theoretical support for the foundational research and application development of jellyfish toxins, as well as a scientific basis for practical applications, including antivenom serum development and novel marine drug design. Full article

Snakebite envenoming remains a major global health challenge. Naja atra (N. atra) envenomation induces severe acute kidney injury (AKI), largely driven by snake venom phospholipase A₂ (SVPLA₂). Increasing evidence suggests that immune dysregulation, in addition to direct cytotoxicity, contributes to delayed renal injury. Here, we investigated whether N. atra SVPLA₂ exposure is associated with macrophage immunometabolic remodeling and functional changes relevant to AKI progression. In vivo, AKI was induced in C57BL/6J mice by intraperitoneal administration of N. atra venom, followed by treatment with the SVPLA₂ inhibitor varespladib. In vitro, bone marrow–derived macrophages were exposed to venom with or without varespladib. N. atra venom exposure was associated with extensive tubular apoptosis, increased renal macrophage abundance, and elevated kidney injury biomarkers. Macrophages exhibited a shift toward a pro-inflammatory polarization signature accompanied by reduced efferocytic capacity. Targeted metabolomics revealed coordinated increases in glycolytic intermediates together with upregulation of key glycolytic enzymes. Pharmacological inhibition of SVPLA₂ partially restored macrophage metabolic features and efferocytic capacity and was accompanied by attenuation of renal injury. Together, these findings support a model in which SVPLA₂ exposure is associated with macrophage immunometabolic remodeling and impaired apoptotic cell clearance during venom-induced AKI. Full article

Tetrodotoxin (TTX), widely known as pufferfish venom, is a low-molecular-weight guanidinium neurotoxin. It can accumulate to extremely high concentrations in certain animals, including pufferfish, blue-ringed octopuses, flatworms, and nemerteans. However, the origin of TTX and the mechanisms that enable such extreme accumulation in these animals remain poorly understood. In this study, using confocal laser scanning microscopy combined with electron immunocytochemistry and ultrastructural analysis, we demonstrate the presence of TTX-positive bacteria associated with specialized cellular structures—type II phagosomes of gut enterocytes—in the highly toxic nemertean Cephalothrix cf. simula. We hypothesize that TTX production in C. cf. simula results from interactions between the nemertean host and its endosymbionts. These findings clarify the origin and accumulation of the toxin in nemerteans and have broader implications for other TTX-bearing species. Full article

Yamakagashi (Rhabdophis tigrinus) is a widely distributed snake species in Japan. Yamakagashi causes venom-induced consumption coagulopathy (VICC) when the amount of infused venom is high, and bites can be fatal if antivenom treatment is delayed. However, yamakagashi antivenom is an unapproved treatment, and its storage capacity is limited, preventing its prompt administration. Therefore, we investigated the application of commercially available drugs, namely tranexamic acid and antithrombin III, in the treatment of VICC caused by yamakagashi venom in a rat model. Furthermore, we investigated the combination of each drug with recombinant thrombomodulin α. Administration of tranexamic acid or antithrombin III alone failed to extend rat survival or correct changes in blood coagulation markers, such as prothrombin time, fibrinogen concentrations, and D-dimer levels, in yamakagashi venom-treated rats. However, combined administration of recombinant thrombomodulin α and tranexamic acid extended rat survival and partially restored blood coagulation markers. Therefore, the combination of recombinant thrombomodulin α and tranexamic acid might represent a useful therapeutic regimen for yamakagashi venom exposure. Full article

The predatory bug Arma custos (Hemiptera: Pentatomidae) is a natural enemy insect capable of preying on over 40 types of agricultural and forestry pests. Here, we describe the characteristics of the morphology and ultrastructure of its venom apparatus visualized using light and electron microscopy. Light microscopy revealed that the venom apparatus of A. custos consists of a pair of main gland and tubular accessory gland. The main gland consist of two lobes, the anterior main gland (AMG) and posterior main gland (PMG). Between the two lobes of the main gland, there is a strong constriction, characterizing a hilum (Hi) where two separate ducts, the venom duct of the main gland (VD) and the duct connecting the accessory gland to the main gland (AMD), are inserted. The VD extends toward the head and connects to the venom pump (VP), while the AMD extends toward the thorax and connects to the accessory gland (AG). Ultrastructural examination of the venom glands reveals that the AMG and PMG consist of a layer of cubic or spherical glandular cells forming a large circular lumen, while the AG exhibits two narrow lumens. The secretory cytoplasm of AMG, PMG, and AG contains a well-developed rough endoplasmic reticulum, along with mitochondria, nuclei, secretory vesicles, autophagosomes, and secretory granules. However, significant differences exist in the ultrastructural characteristics among the three glands. Unlike glandular secretory cells in the venom glands, the ultrastructure of VD, and AMD reveals only well-developed nuclei, mitochondria, and elaborate plasma membrane folds. These results indicate that venom proteins are synthesized and stored by the AMG, PMG, and AG, while the VD and AMD ducts are responsible for transporting the venom. Full article

Encephalitozoon cuniculi is an atypical, opportunistic, obligate intracellular fungal pathogen that infects vertebrates. It survives within the host by modulating the host immune response. Crotoxin (CTX), a bioactive compound isolated from the venom of Crotalus durissus terrificus, has been reported to modulate immune responses. This study evaluated the effects of CTX on the immune response of mice infected with E. cuniculi. Mice were immunosuppressed with cyclophosphamide (Cy), infected with E. cuniculi spores, and treated with a single dose of CTX on the day of experimental. The animals were euthanized on day 14 post-infection. Levels of T helper (Th1, Th2, and Th17) cytokines were measured in plasma, and macrophage and lymphocyte populations were analyzed in peritoneal lavage fluid and spleen. In addition, histopathological alterations, hepatic fungal burden, and mRNA expression levels of NLRP3 inflammasome–related genes were assessed. CTX upregulated NLRP3 inflammasome expression and increased IL-18 production, while reducing fungal burden in E. cuniculi-infected mice. Moreover, CTX increased the proportions of macrophages and B cells and enhanced IFN-γ expression in CD4⁺ and CD8⁺ T lymphocytes. Collectively, these findings indicate that CTX reduces fungal load in Cy-immunosuppressed mice infected with E. cuniculi by priming the NLRP3 inflammasome complex and upregulating IL-18 production. Full article

The easily defanged myth that baby rattlesnakes (genera Crotalus and Sistrurus) are more dangerous than adults has persisted in North America despite all evidence to the contrary. The most often cited reason for the babies-more-dangerous (BMD) myth is the venom-dump (VD) hypothesis: babies, in contrast to adults, cannot control how much venom they expend, and therefore inject all of it when biting. We undertook three approaches to explore the origin, transmission, and prevalence of this myth and its most frequent explanation. First, we examined historical newspaper accounts. From 130 newspaper stories mentioning the relative danger of baby rattlesnakes, we identified a timeline in which (1) most stories prior to 1969 were factually correct; (2) the BMD myth and VD hypothesis likely originated in the mid-to-late 1960s and became entrenched in California, especially, from 1970 to 1999; (3) factually incorrect statements subsequently prevailed throughout North America from 2000 to 2014; and (4) factually correct stories regained prominence with apparent effective messaging success from 2015 onward. We further learned that general information stories about rattlesnakes, more often citing subject experts like university professors, were much more likely to provide accurate information than local snakebite stories, which more often cited health professionals (e.g., physicians, veterinarians, pharmacists) and emergency responders (e.g., police and fire officers) who frequently supplied misinformation. Second, we surveyed familiarity with the BMD myth and VD hypothesis among 53 university classrooms (including one high school) representing 3751 students across 29 states within the United States. Consistent with the California media’s outsized influence on misinformation transmission, familiarity with the myth was greatest in the southwestern states (52.6%) and declined moving north and east, with the least familiarity in the northeastern states (16.4%). Third, a small survey of 75 emergency responders and health professionals from Southern California revealed that a whopping 73.3% actually believed the BMD myth. Numerous organizations generally regarded as authoritative further amplified the misinformation, especially on the internet, where some content persists to this day. Unfortunately, belief in the BMD myth and VD hypothesis can lead to negative consequences, including misinformed risk-taking by those encountering snakes, unwarranted fear among snakebite victims, and inappropriate care delivered by misinformed or patient/family-pressured medical professionals. Our findings target health professionals and emergency responders as priority audiences for education. Full article