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Scorpion stings are a significant public health concern globally, particularly in tropical and subtropical regions. Scorpion venoms contain a diverse array of bioactive peptides, and different scorpion species around the world typically exhibit varying venom profiles, resulting in a wide range of envenomation symptoms. Despite their harmful effects, scorpion venom peptides hold immense potential for drug development due to their unique characteristics. Therefore, the establishment of a comprehensive database that catalogs scorpions along with their known venom peptides and proteins is imperative in furthering research efforts in this research area. We hereby present ScorpDb, a novel database that offers convenient access to data related to different scorpion species, the peptides and proteins found in their venoms, and the symptoms they can cause. To this end, the ScorpDb database has been primarily advanced to accommodate data on the Iranian scorpion fauna. From there, we propose future community efforts to include a larger diversity of scorpions and scorpion venom components. ScorpDb holds the promise to become a valuable resource for different professionals from a variety of research fields, like toxinologists, arachnologists, and pharmacologists. The database is available at https://www.scorpdb.com/. Full article

Background: Coleoptera is the second-most significant insect group associated with decomposing carcasses, yet its role in the decomposition process and postmortem colonization following envenomation is poorly understood. Purpose of the Study: This study aimed to investigate the effects of the venoms from Cerastes cerastes and Naja haje on the decomposition of rabbit carcasses while evaluating the main beetle taxa attracted to these decaying remains. Methods: Three groups of rabbits, each with five individuals, were utilized. The first group was injected with the venom of Cerastes cerastes, the second with Naja haje venom, and the control group received 0.85% physiological saline before euthanasia with CO₂. Results: Four decomposition stages (fresh, bloating, decay, and dry) with durations varying based on venom type and carcass condition were observed. A total of 647 individual beetles of six species (Necrobia rufipes, Attagenus sp., Dermestes frischii, D. maculatus, Bledius sp., and Apentanodes sp.) belonging to four families (Cleridae, Dermestidae, Staphylinidae, and Tenebrionidae) were collected and identified. D. maculatus was the most abundant species. Fewer beetles were attracted to carcasses envenomed with N. haje compared to the other groups. Conclusions: Envenomation by snake venom influences the attraction and succession rate of necrophilous coleopterans to carcasses, which is important for forensic investigations. Full article

Animal venom and plant extracts have been used since ancient times in traditional medicine worldwide. Natural components, valued for their safety and effectiveness, have been consistently used in cosmetic and pharmaceutical applications. We propose a journey along the boulevard of active compounds from natural sources, where bee venom (BV), cobra venom (CV), and Ficus carica reveal their individual therapeutic and cosmetic properties. The originality of this review lies in exploring the synergy of these bioactive sources, an approach that has not been presented in the literature. Although BV, CV, and Ficus carica have different origins and compositions, they have multiple common pharmacological and cosmetic actions, which make them ideal for inclusion in various products that can be used for skin care and health in general. Their anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, neuroprotective, and regenerative properties give them an essential role in the creation of potential innovative and effective products in the pharmaceutical and cosmetics industry. Although many plant extracts have antioxidant and anti-inflammatory properties, Ficus carica was chosen due to its complex biochemical composition, which provides valuable benefits in skin regeneration and protection against oxidative stress. According to the International Nomenclature of Cosmetic Ingredients (INCI), Ficus carica is used in the form of an extract of fruits, leaves, juice, bark or stem, each having specific applicability in topical formulations; due to the diversity of bioactive compounds, it can amplify the effectiveness of BV and CV, helping to enhance their beneficial effects and reducing the risk of adverse effects, due to its well-tolerated nature. Thus, this combination of natural ingredients opens up new perspectives in the development of innovative products, optimizing efficiency and maintaining a favorable safety profile. In this context, due to the reported experimental results, the three natural sources caught our attention, and we conceived the present work, which is a review made following the analysis of the current progress in the study of the bioactive compounds present in BV, CV, and Ficus carica. We focused on the novelties regarding pharmacological and cosmetic actions presented in the literature, and we highlighted the safety profile, as well as the modern approaches regarding the delivery and transport systems of the active substances from the three natural sources, and we evaluated their prospects in therapeutic and cosmetic use. This paper not only expands our knowledge of bioactive compounds, but it can also generate new ideas and motivations for the research and development of innovative treatments and skincare methods. Full article

Kraits are venomous snakes of the genus Bungarus from the family Elapidae. Their venom typically demonstrates neurotoxicity; however, the toxicity is significantly influenced by the snake’s species and geographical origin. Among the Bungarus species, Bungarus suzhenae and B. bungaroides have been poorly studied, with little to no information available regarding their venom composition. In this study, a proteomic approach was employed using LC-MS/MS to identify proteins from trypsin-digested peptides. The analysis revealed 102 venom-related proteins from 18 distinct functional protein families in the venom of B. suzhenae, with the primary components being three-finger toxins (3-FTx, 25.84%), phospholipase A₂ (PLA₂, 40.29%), L-amino acid oxidase (LAAO, 10.33%), Kunitz-type serine protease inhibitors (KUN, 9.48%), and snake venom metalloproteinases (SVMPs, 6.13%). In the venom of B. bungaroides, 99 proteins from 17 families were identified, with primary components being 3-FTx (33.87%), PLA₂ (37.91%), LAAO (4.21%), and KUN (16.60%). Enzymatic activity assays confirmed the presence of key venom enzymes. Additionally, the LD50 values for B. suzhenae and B. bungaroides were 0.0133 μg/g and 0.752 μg/g, respectively, providing a reference for toxicity studies of these two species. This research elucidates the proteomic differences in the venoms of these two species, offering a foundation for developing antivenoms and clinical treatments for envenomation. Full article

Physalia physalis, commonly known as the Portuguese Man o’ War, is one of the most venomous members of the Cnidaria yet is poorly understood. This article investigates the toxicity of P. physalis venom by assessing its behavioral and toxicological effects on Drosophila melanogaster. The venom administered orally revealed dose- and time-dependent mortality, with an LD50 of 67.4 μg per fly. At sublethal doses, the treated flies displayed uncoordinated movement and fell when attempting to climb. Real-time analysis of flies exposed to the venom revealed hyperexcitability followed by paralysis, with phenotypes similar to those observed in vertebrate models. The venom was shown to be non-thermolabile, as no significant differences in behavior and locomotion were observed between flies exposed to untreated or thermally treated venom. The circadian rhythm alterations, the enhanced light attraction, and the reduction in heat avoidance suggest altered neuronal function. This abnormal behavior indicates that the venom contains bioactive molecules, opening avenues for discovering new compounds with potential for pharmacological applications. Full article

Cross-reactive carbohydrate determinants (CCDs) are complex N-glycans shared among allergens of plant, insect venom, and nematode origin. In allergic humans, IgE anti-CCD often develop and cause discrepancies between serological and skin tests. Overall, CCD-IgE are believed to be of low pathogenic relevance. IgE-targeting CCDs are also detected in companion animals, but their pathogenic potential and biological relevance are unknown. Herein, we first establish that, in 34 dogs with atopic dermatitis, the presence of serum anti-CCD IgE was detected in 14 pets (41.2%). In dogs, as in humans, IgE-targeting CCDs are heterogeneous, as they differentially recognized four distinct CCD-expressing proteins. The presence of CCD-IgE was associated with a higher and more frequent recognition of plant extracts in serological but not intradermal tests. Two different CCD-expressing proteins did not elicit immediate reactions when injected intradermally in dogs with detectable serum anti-CCD IgE. Similarly, two different CCD-expressing proteins did not induce the activation of mast cells passively transferred with canine anti-CCD IgE. Altogether, these results suggest that in dogs, as in humans, anti-CCD IgE are likely to have little pathogenic potential and blocking them in allergen-specific IgE serological tests is warranted to avoid false-positive results to plant extracts. Full article

Chronic urticaria is one of the most common diseases in allergology and dermatology practice with unclear causes of occurrence. Background: Some studies emphasize the correlation between inflammation in chronic urticaria and disturbed intestinal microbiota. It raises the question about the role of some intestine-related substances in the pathogenesis of urticaria as well as their potential role as disease predictors. Calprotectin is an acute-phase protein with a well-established diagnostic position in the field of gastroenterology. There are some data on the relationship between this parameter and gut microbiota. The major aim of this preliminary study is to investigate whether calprotectin can be potentially taken into account as a disease course predictor in urticaria. Methods: We included in our study 54 chronic spontaneous urticaria (CSU) patients (of whom 26 manifested the symptoms of recurrent angioedema) and 29 patients allergic to Hymenoptera venom for the reference group (in these patients, before venom immunotherapy induction, full diagnostics is performed including intestinal problems). Disease activity in the CSU patients was assessed using the Urticaria Activity Score (UAS) and the disease control in this group was assessed with the Urticaria Control Test (UCT). Moreover, we analyzed fecal and serum calprotectin concentrations. Results: Positive correlation was found only between the values of serum calprotectin concentration and the control level of CSU symptoms with the lack of other relations. Conclusions: Our results do not supply unequivocal evidence for calprotectin as a potential marker of CSU course, though this concept, in the light of growing evidence for microbiota’s role in urticaria, requires further research. Full article

Hymenoptera, which includes honeybees, wasps, bumblebees, and hornets, is an order of the class Insecta, whose venom can induce anaphylactic reactions in dogs. While several studies have investigated the natural histories and risk factors of Hymenoptera venom allergy (HVA) in humans, only limited information is available on canine patients. Therefore, the aim of this study was to identify risk factors leading to severe systemic reactions (SSRs) and to explore the natural history of these patients. This was achieved with an inquiry into the case histories of 178 dogs that were stung by Hymenoptera and presented to the Vetsuisse Faculty Animal Hospital of the University of Zurich between 2018 and 2022. Dogs under two years old, dogs that weighed under 10 kg, purebred dogs, and dogs that were stung in the oral cavity were at a greater risk of developing SSRs. Almost two thirds of patients with SSRs experienced the same or worse symptoms after subsequent stings and >40% of patients with local reactions developed SSRs when stung again. Next to providing valuable clinical information about HVA in dogs, these findings strongly support the recommendation of venom immunotherapy (VIT) for patients with HVA. Full article

Viperid snake venoms are notably abundant in metalloproteinases (proteins) (SVMPs), which are primarily responsible for inducing hemorrhage and disrupting the hemostatic process and tissue integrity in envenomed victims. In this study, barnettlysin-III (Bar-III), a hemorrhagic P-III SVMP, was purified from the venom of the Peruvian snake Bothrops barnetti. Bar-III has a molecular mass of approximately 50 kDa and is a glycosylation-dependent functional metalloproteinase. Some biochemical properties of Bar-III, including the full amino acid sequence deduced from its cDNA, are reported. Its enzymatic activity is increased by Ca²⁺ ions and inhibited by an excess of Zn²⁺. Synthetic metalloproteinase inhibitors and EDTA also inhibit its proteolytic action. Bar-III degrades several plasma and ECM proteins, including fibrin(ogen), fibronectin, laminin, and nidogen. Platelets play a key role in hemostasis and thrombosis and in other biological process, such as inflammation and immunity, and platelet activation is driven by the platelet signaling receptors, glycoprotein (GP)Ib-IX-V, which binds vWF, and GPVI, which binds collagen. Moreover, Bar-III inhibits vWF- and convulxin-induced platelet aggregation in human washed platelets by cleaving the recombinant A1 domain of vWF and GPVI into a soluble ectodomain fraction of ~55 kDa (sGPVI). Bar-III does not reduce the viability of cultured endothelial cells; however, it interferes with the adhesion of these cells to fibronectin, vitronectin, and RGD peptides, as well as their migration profile. Bar-III binds specifically to the surface of these cells, and part of this interaction involves α5β1 integrin receptors. These results contribute to a better comprehension of the pathophysiology of snakebite accidents/incidents and could be used as a tool to explore novel and safer anti-venom therapeutics. Full article

Background: Andexanet alfa is a specific antidote for factor Xa (FXa) inhibitors. It is licensed to treat patients under FXa inhibitor therapy with life-threatening bleeding. Concomitantly, volume expanders are used to compensate for blood loss and maintain circulation. The competitive binding of andexanet to FXa inhibitors may be disrupted due to hemodilution, as shown by laboratory assays with high sample dilution. This study investigated the efficacy of andexanet for the reversal of FXa inhibitors under hemodilution. Methods: Blood from 10 healthy volunteers was anticoagulated with rivaroxaban and subsequently treated with four different volume expanders (Ringer’s solution, 4% gelatine, 5% and 20% human albumin (HA)) at two dilution levels (20% and 50%). After anticoagulation and hemodilution, andexanet was added according to the high-dose protocol. Blood samples were analyzed using a Russell’s viper venom (RVV) test on a Clot Pro^® device, a thrombin generation assay, a fully automated coagulation analyzer and a chromogenic anti-FXa activity assay. Results: After anticoagulation, the median rivaroxaban concentration was 272 ng/mL (IQR 254–353). Anticoagulation with rivaroxaban caused a significant impairment of all coagulation parameters, which was further aggravated by hemodilution. After the administration of andexanet, coagulation parameters in anticoagulated samples were reversed to near baseline in all groups. Andexanet administration decreased the rivaroxaban plasma concentration in all groups to a median of <10 ng/mL. In the anticoagulated, non-hemodiluted samples, anti-FXa activity was reduced by 98%. The anti-FXa activity in the anticoagulated, hemodiluted samples was reduced by approximately 96% in the 20% diluted samples and by about 93% in the 50% diluted samples. Conclusions: Our data indicate that FXa inhibitor reversal with andexanet is about 5% less effective with 50% hemodilution than in non-hemodiluted samples. Full article

Conotoxins are small and highly potent neurotoxic peptides derived from the venom of marine cone snails which have captured the interest of the scientific community due to their pharmacological potential. These toxins display significant sequence and structure diversity, which results in a wide range of specificities for several different ion channels and receptors. Despite the recognized importance of these compounds, our ability to determine their binding targets and toxicities remains a significant challenge. Predicting the target receptors of conotoxins, based solely on their amino acid sequence, remains a challenge due to the intricate relationships between structure, function, target specificity, and the significant conformational heterogeneity observed in conotoxins with the same primary sequence. We have previously demonstrated that the inclusion of post-translational modifications, collisional cross sections values, and other structural features, when added to the standard primary sequence features, improves the prediction accuracy of conotoxins against non-toxic and other toxic peptides across varied datasets and several different commonly used machine learning classifiers. Here, we present the effects of these features on conotoxin class and molecular target predictions, in particular, predicting conotoxins that bind to nicotinic acetylcholine receptors (nAChRs). We also demonstrate the use of the Synthetic Minority Oversampling Technique (SMOTE)-Tomek in balancing the datasets while simultaneously making the different classes more distinct by reducing the number of ambiguous samples which nearly overlap between the classes. In predicting the alpha, mu, and omega conotoxin classes, the SMOTE-Tomek PCA PLR model, using the combination of the SS and P feature sets establishes the best performance with an overall accuracy (OA) of 95.95%, with an average accuracy (AA) of 93.04%, and an f1 score of 0.959. Using this model, we obtained sensitivities of 98.98%, 89.66%, and 90.48% when predicting alpha, mu, and omega conotoxin classes, respectively. Similarly, in predicting conotoxins that bind to nAChRs, the SMOTE-Tomek PCA SVM model, which used the collisional cross sections (CCSs) and the P feature sets, demonstrated the highest performance with 91.3% OA, 91.32% AA, and an f1 score of 0.9131. The sensitivity when predicting conotoxins that bind to nAChRs is 91.46% with a 91.18% sensitivity when predicting conotoxins that do not bind to nAChRs. Full article

The pine wood nematode (Bursaphelenchus xylophilus), the pathogen of pine wilt disease (PWD), has caused enormous economic losses in Asian forests. Whether venom allergen proteins (VAPs) are involved in the accumulation of key defense substances in pine trees during the interaction between B. xylophilus and host trees, and their specific function as putative effectors secreted through stylets, has not been fully elucidated. In this study, the role of the BxVAP2 effector protein in the infection process was analyzed through bioinformatics and phylogenetic tree construction. The expression profile of BxVAP2 during infection was analyzed using qRT-PCR, and its expression under the stress of Pinus massoniana metabolites was examined. Toxicity assays were conducted through the Agrobacterium transient expression of BxVAP2 in Nicotiana benthamiana, and its subcellular localization was investigated. The results showed that BxVAP2 contains a CAP domain and shares close evolutionary relationships with venom allergen proteins from related species, such as Bursaphelenchus mucronatus, Aphelenchoides besseyi, Aphelenchoides fujianensis, and Meloidogyne graminicola. BxVAP2 was upregulated during the infection of P. massoniana, indicating that BxVAP2 is a key effector in the infection and colonization process of B. xylophilus and may play an important role during the rapid population growth phase. BxVAP2 responds to P. massoniana metabolites, where different concentrations of α-pinene suppressed its expression, while high concentrations of β-pinene promoted its expression. Subcellular localization revealed that BxVAP2 localizes to the cell membrane and nucleus. The transient expression of BxVAP2 in N. benthamiana induced programmed cell death and regulated pattern-triggered immunity marker genes. These findings suggest that BxVAP2 plays an important role in the interaction between B. xylophilus and its host, responding to terpene stress and triggering plant defense. Full article

Spider venoms are emerging as a rich source of bioactive peptide toxins with therapeutic potential. Lynx spiders of the genus Oxyopes are small, cursorial hunters that employ complex venom to subdue arthropod prey. However, extracting crude venom from these diminutive arachnids poses significant challenges. This study presents a transcriptome analysis of venom glands from an undescribed Oxyopes forcipiformis species, revealing 339 putative protein and peptide toxin sequences categorized into seven functional groups. The venom composition was dominated by membrane-active peptides (40.71%), venom auxiliary proteins (22.71%), neurotoxins (15.63%), channel active peptides (7.08%) and uncharacterized components (13.87%). Additionally, phylogenetic analysis of 65 disulfide-bond-rich peptides yielded six distinct families based on sequence homology and cysteine framework. Finally, a novel antimicrobial peptide, GK37, was identified using in silico and homology analyses. Our data suggested that GK37 presented significant antibacterial activity against Gram-positive bacteria Staphylococcus aureus with a minimum inhibitory concentration (MIC) of 1.552 µM by disrupting bacterial membranes. At 4× MICs, GK37 almost showed no hemolytic activity on blood cells or toxicity against Hek293T cells. Our findings provided a basis for targeted studies of the diversity and pharmacological effects of lynx spider peptide. We elucidated a valuable high-throughput approach for obtaining proteins and peptides from small-group spiders. Full article

Bee venom acupuncture, a type of herbal acupuncture, combines the pharmacological actions of bioactive compounds from bee venom with the mechanical stimulation of meridian points. Bee venom acupuncture is gaining popularity, particularly in the Republic of Korea, primarily for pain relief of various conditions. This study aimed to summarize and evaluate the available evidence on the use of bee venom acupuncture for recovery after bone fractures. Electronic literature searches for experimental studies and clinical trials were conducted using the PubMed, China Academic Journals (CAJ), and OASIS databases. The search revealed 31 studies, of which six met our criteria. These studies demonstrated that bee venom acupuncture can be effective in treating bone fractures, suggesting a promising area for future research. However, evidence supporting its efficacy in this context is limited. Rigorous trials with large sample sizes and robust designs are needed to clarify the role of bee venom acupuncture for these indications. In addition, future studies should explore the optimal dosage and concentration of bee venom acupuncture. Full article

Wasp venom allergy can trigger severe allergic reactions, and predicting these acute responses remains challenging. This study evaluates the utility of immune system indexes, particularly the eosinophil–basophil/lymphocyte (EB/LR) and eosinophil–basophil–platelet/lymphocyte (EBP/LR) ratios, in assessing the severity of allergic reactions in patients with wasp venom allergy. A total of 61 patients with confirmed wasp venom allergy were categorized according to the Mueller scale, which classifies the severity of allergic reactions. Blood samples were analyzed for total and specific IgE levels alongside a range of hematological and biochemical parameters. This study found significant differences in the EB/LR and EBP/LR indexes between patients with mild (Mueller I–II) and severe (Mueller III–IV) allergic reactions, with higher values indicating more severe responses. However, no significant differences were observed in other immune indexes, such as the platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, and systemic inflammatory response index, as well as in additional blood parameters. These findings suggest that the EB/LR and EBP/LR ratios may serve as useful markers for predicting the severity of allergic reactions in patients with wasp venom allergy. This is the first study to establish such a link, although further research with larger cohorts is necessary to confirm these results and their potential application in clinical settings. Full article