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Evolutionary innovation is a key driver of the colonization of new environments and the adaptive radiations of major groups. Novel traits typically evolve through the modification of pre-existing characters but the genetic paths underlying their origin have been challenging to trace, and the general requirements for and relative order of different kinds of gene mutations have been difficult to assess. Here, we trace the genomic origins of four procoagulant venom toxins (factor X, factor V, group I phospholipase A ₂ , and Kunitz-type toxins) that collectively underlie a novel, especially potent blood-clotting venom type in the recently evolved Australian brown snake and taipan clade. We discover evidence for a previously unknown fifth toxin, coagulation factor VII, and show that the toxins evolved through two distinct genetic paths. The factor X and factor V toxins evolved through the sequential de novo co-option of ancestral clotting factor proteins that entailed their heterotopic expression in the venom gland, the fixation of segmental duplications containing each locus, and subsequent gain-of-function mutations that rendered factor X and factor V constitutively active. In contrast, the phospholipase A ₂ and Kunitz-type toxins evolved by modifying the functions of neurotoxins that were part of the venom arsenal. Our findings support models in which innovative mutations in single-copy genes precede gene duplication in the evolution of novel proteins and offer a rare view into the genesis of a complex trait that has played a central role in a major adaptive radiation. This study investigates how an entirely new blood-clotting venom type evolved during the recent radiation of Australia's iconic venomous snakes. We traced the key genetic events that occurred on the evolutionary path to one of the world's most potent venoms. We found that the novel venom activity evolved through the sequential co-option of multiple proteins of the snake's own blood-clotting system, followed by the modification of two venom neurotoxins into proteins with procoagulant activities. We suggest that these unique de novo gene co-options are seminal events that can unlock new ecological strategies, which in turn, may enable major adaptive radiations.
Snakebite envenomation is a major public health issue in tropical regions like South India, yet its psychological consequences, particularly post-traumatic stress disorder (PTSD), remain underexplored. To evaluate mental health outcomes and identify risk factors for PTSD among snakebite survivors. This prospective observational study enrolled 98 adult snakebite patients at a tertiary care center, selected based on inclusion criteria and data completion. Sociodemographic, bite incident, and clinical data were collected via semi-structured interviews. PTSD severity was assessed longitudinally over 6 months using the short PTSD rating interview (SPRINT) scale. Chi-square tests and logistic regression analyzed associations between variables and PTSD. Of the 98 participants, 38.78% developed PTSD (21.43% mild, 15.31% moderate, 2.04% severe). Significant associations with PTSD included rural residence (P = 0.012, OR = 1.98, 95% CI: 1.16-3.39), venomous snakebites (P < 0.001, OR = 2.45, 95% CI: 1.32-4.56), bite site (P = 0.003), loss of consciousness (P = 0.002, OR = 3.12, 95% CI: 1.67-5.83), and delayed hospital arrival (>4 hours, P = 0.004, OR = 2.89, 95% CI: 1.45-5.76). PTSD is a significant concern among snakebite survivors, with identifiable risk factors. Integrated care combining medical and psychological interventions is essential for recovery. Future longitudinal studies and targeted interventions are needed.
Snakes are becoming increasingly popular companion animals in Bulgaria, yet their potential as zoonotic pathogen reservoirs remains underexplored. This study examined the presence of bacteria in captive pet snakes and assessed the public health risks associated with their handling. Bacteriological analysis was conducted on 29 snake samples from pythons, boas, corn snakes, and one venomous species. Each individual was nurtured in a carefully controlled environment, receiving a specialized diet primarily consisting of frozen rodents. This approach ensures optimal health and well-being. Standard microbiological techniques were used for bacterial isolation and identification, and the results were confirmed using the Vitek 2 Compact System. Salmonella enterica (group B) was isolated from eight samples, indicating a notable prevalence of this pathogen among the examined snakes. Several other bacterial genera were identified, including Pseudomonas spp., Staphylococcus spp., Proteus spp., Enterobacteriaceae spp., Sphingomonas paucimobilis, Enterococcus spp., Bacillus spp., Achromobacter denitrificans, Citrobacter koseri, and Klebsiella pneumoniae. The study highlights the potential zoonotic risks associated with snake keeping, particularly when reptiles come in direct contact or are exposed to contaminated environments. Food sources can act as potential transmission mechanisms for microbial contamination. It is essential to adopt strict hygiene practices, conduct regular monitoring of snake health, and implement appropriate feeding and cleaning protocols to minimize the risk of bacterial transmission between snakes and humans.
In many cultures, snakes are perceived in a markedly negative light, causing hostile attitudes, fear and phobias in people, which often leads to their persecution and killing. Studies on human perceptions of snakes are typically survey-based, while people's ability to detect them is usually conducted under controlled artificial conditions. Studies that simulate natural circumstances of human-snake encounters, however, remain scarce. The present study recreated natural human-snake encounters by conducting in situ experiments with viper models and carcasses, in order to assess tourists' ability to detect vipers (Vipera berus and Vipera ammodytes) and to evaluate their reactions. Most people did not detect the vipers when they were placed on the tourist paths, and almost none detected vipers positioned in the grass next to the paths. On the paths, adult vipers were detected significantly more often than juveniles. Most tourists showed interest and no signs of fear during their encounters with the vipers, while a very small number of people exhibited strong fear or aggressive behavior. Tourists were more likely to display no interest and moderate fear toward adult vipers than toward juveniles. Most participants were able either to correctly identify the species or at least recognize that the snake was venomous. These results demonstrate that this innovative approach provides valuable insights into different aspects of human-snake interactions and highlight the usefulness of snake models in such studies.
Potassium (K+) channels are targeted by a wide range of chemical and biological substances, with peptide ligands standing out due to their exceptional affinity and selectivity. Although most of these molecules belong to venom-derived compounds, novel ligands from various less investigated or less popular sources are being discovered. Application of polypeptides is not restricted to fundamental studies and can be expanded to drug discovery, clinical pharmacology, and pharmaceutics. In this report, we offer a concise overview of the diversity of K+ channel ligands and their sources, briefly summarizing recent developments in the field and providing an outlook. SIGNIFICANCE STATEMENT: This paper provides a concise overview of the diversity of K+ channel ligands and their natural sources, highlights recent advances, and outlines future directions. Although venom-derived polypeptides remain the main source, growing interest is focused on nonvenomous organisms such as plants and mammals. We also discuss artificial polypeptides developed using mutagenesis, and the potential of machine learning and neural networks as promising tools for further molecular design.
Emerging antibiotic-resistant Vibrio spp. strains have caused recurrent outbreaks, resulting in substantial losses in shrimp farming and aquaculture production. This ongoing crisis calls for innovative strategies to mitigate its impact, particularly in resource-limited countries that depend heavily on the shrimp industry. In this context, biodiscovery initiatives focused on snake venom toxins with antimicrobial properties represent a promising alternative. Accordingly, we investigated the anti-Vibrio activity of a catalytically inactive phospholipase A₂ (Lys49 PLA₂) purified from the venom of Bothrops asper, a venomous snake commonly found in Ecuador. This novel bioactive biomacromolecule, termed BaETx, was isolated from a venom pool using a one-step purification approach. Mass spectrometry analysis revealed a molecular mass of 13.6 kDa, consistent with its electrophoretic mobility in one-dimensional SDS-PAGE. Structurally, BaETx exhibits high similarity to the amino acid sequences of PLA₂s previously reported from B. asper venoms in other geographical regions. Bioactivity screening demonstrated that BaETx significantly inhibited the in vitro growth of three Gram-negative Vibrio spp. pathogens. Further mechanistic insights obtained through electron and fluorescence microscopy suggest a membrane-damaging actitvity. However, BaETx also significantly reduced shrimp hemocyte viability, indicating non-selective action and limiting its direct application in aquaculture. In addition, computational sequence analysis identified cationic antimicrobial fragments that warrant further investigation. Overall, this study reports the first purification and characterization of an antimicrobial protein from Ecuadorian snake venom, highlighting its potential as a molecular template for the development of shorter and more selective synthetic peptides targeting white shrimp pathogens.
Snakebite envenomation poses a significant health threat worldwide, and Echis ocellatus, one of the highly venomous snakes in West Africa, partly contribute to this menace. Traditional antivenoms are expensive, not widely available in many prevalent regions, and may cause adverse reactions, creating the need for an alternative approach to snakebite treatment. The study investigated the production of chicken egg yolk-derived immunoglobulin Y (IgY) from Echis ocellatus venom, assessed their neutralization efficacy, and compared the effect of different adjuvant treatments in enhancing high antibody titres. Sublethal dose of the venom induced an immune response in the chicken as evidenced in the SDS-PAGE analysis with prominent protein bands of approximately (70kDa and 25kDa). The specificity of the IgY with the venom was duly confirmed with the presence of a clear precipitin line between the venom and IgY wells. Among the adjuvants tested, Freund's adjuvant produced the highest IgY concentration (11.5 mg/ml) during the second immunization cycle, whilst the Alum produce the least IgY concentration (10.7 mg/ml). The purified IgY effectively neutralized 3LD50 (2.16 mg/kg body weight) of the venom with an ED50 of 25.57 mg/kg body weight. Additionally, 320μg of IgY successfully neutralised 3 Minimum Haemorrhagic Dose (5.1μg) and 3 Minimum Oedematic Dose (7.32μg) without any signs of envenomation. The study successfully produced IgY from chicken egg yolk using Freund's adjuvant and also highlighted the potential of IgY as an alternative option to traditional antivenoms for treating Echis ocellatus envenomation.
HP1090 is a short, cationic, amphipathic peptide derived from scorpion venom and previously described as a membrane-active antiviral compound. Here, we primarily characterize the antiviral activity of HP1090 and assess whether additional antibacterial effects are consistent with membrane-disruptive properties. Chemically synthesized HP1090 exhibited dose-dependent virucidal activity against multiple enveloped viruses, including herpes simplex virus type 1 and 2 (HSV-1, HSV-2), human immunodeficiency virus type 1 (HIV-1), and Zika virus (ZIKV), with IC50 values ranging from 14.7 to 56.1 µg/mL. No activity was observed against the non-enveloped human rhinovirus 14 (HRV14), suggesting strict dependence on a viral lipid envelope. Consistent with a membrane-targeting mechanism, HP1090 induced rapid and concentration-dependent permeabilization of virus-like liposomes. HP1090 also displayed antibacterial activity against selected clinically relevant pathogens in agar-based growth inhibition assays. However, antibacterial effects required substantially higher concentrations (>125 µg/mL) and varied between bacterial species, with some strains showing little or no susceptibility. Membrane permeabilization assays in Listeria monocytogenes demonstrated disruption of bacterial membrane integrity as a contributing mechanism. No cytotoxicity was observed on mammalian cell lines at effective antiviral concentrations. Together, these findings establish HP1090 as a membrane-active venom peptide and, by linking envelope-dependent viral inactivation with bacterial membrane permeabilization, support a shared biophysical mode of action relevant to the development of membrane-targeting anti-infectives.
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Insect bite hypersensitivity (IBH) is the most common allergic skin disease in horses, but existing clinical scoring systems lack extensive validation, limiting standardized disease monitoring and therapeutic evaluation. Develop and validate a standardized, sensitive, and reproducible clinical scoring system for IBH in horses. Forty-four privately-owned horses with clinically diagnosed IBH examined under field conditions in Switzerland. In this prospective field validation study, the equine IBH severity score (EqIS) integrates a lesion severity score and an area score using a multiplicative algorithm. Six trained evaluators assessed horses independently. Primary outcomes were intra- and interobserver reliability of the lesion severity score and EqIS assessed using intraclass correlation coefficients (ICC). Secondary analyses included agreement of the area score (Pearson correlation), correlations between owner-reported visual analog scale (VAS) scores and EqIS, and comparison between EqIS and a simplified EqIS developed for field use. Intraobserver reliability was excellent (ICC = 0.995 for the lesion severity score and 0.989 for EqIS), and interobserver reliability was similarly high (ICC = 0.98 for both). The area score showed strong interobserver agreement (Pearson r = 0.86-0.94). Owner VAS scores correlated moderately with EqIS (ρ = 0.49-0.51) and strongly with each other (ρ = 0.88). The simplified EqIS demonstrated strong agreement with the validated version (R2 = 0.86). The EqIS is the first extensively validated IBH-specific scoring system and demonstrates excellent reproducibility across evaluators. It provides an objective tool for standardized disease assessment and therapeutic monitoring, whereas the simplified EqIS offers a practical alternative for routine field use.
Background/Objectives: Chronic wounds remain a formidable clinical challenge due to the suboptimal efficacy of conventional delivery systems and therapeutics. Textilinin-1, a venom-derived Kunitz-type serine protease inhibitor, has previously established its profile as a potent hemostatic agent. However, its potential as a multifunctional biopharmaceutical for wound management remains largely untapped. This study evaluates the pharmacological effects of Textilinin-1 in preclinical models of cutaneous wound repair. Methods: We employed an integrated platform comprising bioinformatics, in vitro cellular assays, and in vivo murine excisional wounds and a pilot porcine proof-of-concept model to assess the wound healing-promoting effects of Textilinin-1 and explore associated cellular responses associated with key stages of the wound healing cascade. Results: Textilinin-1 was associated with multiple cellular responses relevant to tissue repair. It attenuated M1-like inflammatory activation and showed preliminary growth-inhibitory activity against Staphylococcus aureus under the tested conditions. Concurrently, it enhanced the proliferative and migratory capacity of fibroblasts, endothelial cells, and keratinocytes, which are key cellular targets for wound closure. In pre-clinical pilot porcine and rodent models, Textilinin-1 treatment was associated with accelerated wound contraction and improved structural tissue quality. Conclusions: Our findings provide preclinical evidence that Textilinin-1 may promote cutaneous wound repair and modulate cellular responses relevant to key stages of the wound healing cascade. These results support further investigation of Textilinin-1 as a candidate for wound repair applications. Future studies are required to define its precise molecular mechanisms, evaluate its efficacy in chronic or otherwise compromised wound models, and optimize its topical formulation or hydrogel-based delivery.
Iron is a necessary trace element in the human body. However, excessive concentration can promote the overproduction of reactive oxygen species, leading to oxidative stress and organ injury. This study aims to evaluate the biochemical and micromorphological changes that occur following exposure to graded doses of ferrous sulfate in a rat model. The treated groups (D1, D2, D3, and D4) were orally and daily treated with graded doses of ferrous sulfate (12.5 mg/kg [D1], 25 mg/kg [D2], 50 mg/kg [D3], and 100 mg/kg [D4]) for 6 weeks, whereas the control group received only saline solution (0.9% NaCl solution at 5 ml/kg body weight) during the same period. Different doses of ferrous sulfate did not cause mortality. Weekly control of glucose levels in all rats revealed a remarkable interaction effect (p = 0.02) between treatment and time, indicating that the dynamics of change over time differed among the groups. Moreover, a significant effect was detected in the time factor (p < 0.001) and in the second factor, which refers to the treatments (p < 0.001). In addition, ferrous sulfate differentially altered the levels of oxidative stress biomarkers, including glutathione, catalase, glutathione-S-transferase, and malondialdehyde, as well as the acetylcholinesterase activity in a dose- and organ-dependent manner. Histopathological examination revealed signs of liver inflammation and pancreatic and kidney hyperemia. Prussian blue staining revealed no significant iron deposits in any organs. Excessive iron may cause oxidative damage to vital organs and alter blood glucose levels.
The cobra diversity of Myanmar has long been a source of confusion, complicating public health responses to snakebites resulting from this medically important genus. By integrating distributional data, natural history information, and clinical evidence, we clarify the composition and distribution of Myanmar's cobra fauna and evaluate the implications for envenoming and snakebite management. We confirm the presence of five cobra species (Naja fuxi, N. kaouthia, N. mandalayensis, N. siamensis, and N. sumatrana) in Myanmar through voucher specimens and/or diagnostic photographic records and identify one additional unconfirmed species (N. sagittifera) that may occur in the country based on distributional proximity. Encounter records showed significant within-year temporal variation, with reports peaking in December and during the dry season. Because data derive from opportunistic citizen science submissions, these patterns likely reflect seasonal differences in detection and human activity rather than biological seasonality. Differences from wet-season peaks reported elsewhere highlight the importance of sampling framework in shaping apparent temporal trends. Review of clinical and toxicological information shows that only one species is represented in locally produced antivenom, raising concern about limited cross-neutralization for other cobra species in the country. Traditional practices remain common in many communities and include harmful methods that delay access to medical care or worsen injuries. Clinical evidence demonstrates that neurotoxicity, respiratory failure, and localized tissue destruction are the principal complications of cobra envenoming, often requiring antivenom therapy, airway support, mechanical ventilation, infection management, and surgical intervention in severe cases. The broader-than-recognized diversity of cobras in Myanmar, combined with high encounter probabilities, synanthropic tendencies, and gaps in public awareness, continues to hinder effective management of snakebite. Improved community education, expanded venom and antivenom research, and timely access to appropriate medical care are essential for reducing the burden of cobra envenomation in Myanmar.
Peripheral nerve injuries severely impair motor function. Although neurorrhaphy is the gold-standard treatment, recovery is often incomplete. The heterologous fibrin biopolymer (HFB), a nonhuman-derived and biocompatible sealant, has shown regenerative potential in neural tissues, but its effects on the spinal cord microenvironment after peripheral nerve injury remain unclear. This study evaluated the chronic regenerative effects of HFB combined with neurorrhaphy after sciatic neurotmesis in rats. Forty adult male Wistar rats were divided into four groups: control, denervated, neurorrhaphy, and neurorrhaphy + HFB. After 120 days, the spinal cord, sciatic nerve, and soleus muscle were analyzed. Neurorrhaphy + HFB had more retrograded label neurons than neurorrhaphy, whereas 3D reconstruction suggests reduced neuronal dispersion compared with neurorrhaphy. HFB also positively modulated glial cells, while improving sciatic nerve integrity, with NF200, S100, and G ratio indicating improved axonal regeneration. Neuromuscular junctions in the HFB-treated group were more organized than those in the neurorrhaphy alone. Overall, findings suggest that HFB acts as a bioactive modulator, preserving central glial homeostasis and enhancing peripheral remyelination and reinnervation, representing a promising adjuvant to overcome the limitations of conventional suture.
Peptide therapeutics have emerged as a versatile class of biomolecules bridging the gap between small-molecule drugs and large biologics. Advantages of such molecules include high target specificity, potent bioactivity and reduced off-target toxicity. Despite these, broader clinical translation remains constrained by inherent limitations like poor metabolic stability, rapid renal clearance, limited membrane permeability and scalable synthesis. This review aims to systematically integrate advances in peptide science across natural discovery, synthetic methodologies, structural engineering, and translational delivery systems, while identifying critical research gaps hindering clinical adoption. We highlight diverse natural sources of bioactive peptides, including plant- (lunasin), animal- (Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP)), microbial- (nisin and cyclosporine), marine- (dolastatins) and venom-derived (chlorotoxin and ω-conotoxin MVIIA (ziconotide)) agents. Advances in solid-phase peptide synthesis (SPPS), green chemistry, and catalytic strategies are discussed alongside emerging in silico approaches, including artificial intelligence-driven sequence design and molecular modeling. Structural modifications such as cyclization, hydrocarbon stapling, PEGylation, and lipidation are critically evaluated for their role in enhancing pharmacokinetic and pharmacodynamic properties. Furthermore, nanoformulation strategies, including self-assembling peptides and cell-penetrating systems, are examined for their potential to overcome biological barriers. Importantly, this review identifies key unresolved challenges, including the lack of predictive models for peptide delivery systems, safety concerns associated with long-term modifications, and limited in vivo validation of naturally derived peptides. Addressing these gaps through integrated computational and experimental approaches will be essential for advancing next-generation peptide therapeutics. Collectively, this work provides a comprehensive framework for the rational design and translation of peptide-based precision medicines.
In many parasitoid insects, especially hymenopteran parasitoids, venom is delivered around oviposition to override host physiology. Once viewed as a narrowly immunosuppressive secretion, parasitoid venom is now recognized as a multifunctional effector system targeting host immunity, development, metabolism, and behavior. This review synthesizes the venom apparatus, identification strategies, mechanisms of host manipulation, evolutionary processes, and biocontrol prospects, drawing primarily on Hymenoptera. A consistent pattern emerges: comparable host phenotypes arise from divergent molecular scaffolds, indicating functional rather than molecular convergence. Mechanistic evidence is strongest along six interlocking axes: inhibition of the prophenoloxidase cascade and melanization, disruption of cellular and humoral immunity, developmental arrest, metabolic reprogramming, and neuromuscular or behavioral manipulation. Outside Hymenoptera, the coleopteran ectoparasitoid Dastarcus helophoroides offers one of the clearest comparative cases: parasitization inhibits host melanization, alters phenoloxidase activity, and reduces antibacterial activity and circulating hemocyte abundance. As of today, fifty putative venom-like candidate proteins have been identified from larval whole-body proteomics, yet the secretory tissue remains anatomically unresolved, and no individual effector has been functionally validated. The central challenge is therefore the transition from candidate catalogs to mechanistically resolved repertoires, particularly outside Hymenoptera. Closing this gap will be important for evolutionary inference and the rational development of venom-based biocontrol tools.
Despite the vast biodiversity of Mexican vipers, venom of endemic species has been barely studied. Here we analyzed the venom composition of three endemic species of rattlesnakes: Crotalus aquilus, C. triseriatus, and C. ravus. We used quantitative chromato-mass-spectrometry and compared venoms with C. molossus, a species commonly found in North America, in a comparative and phylogenetic framework. In total, we identified 165 proteins grouped in 19 main protein families, consistent with previous reports for viperid venoms. In C. aquilus and C. triseriatus, the most predominant protein-family type was Serine Proteases, and in C. triseriatus and C. molossus it was Snake Venom Metalloproteases. The Label-free quantification revealed a high proportion of Snake Venom Metalloproteases in C. aquilus, C. triseriatus, and C. molossus, reaching 28-47% of the total venom. In contrast, in C. ravus 47% of the venom was composed of Phospholipases A2. Among the four species analyzed, C. triseriatus and C. aquilus were most similar in compositional profiles and their profiles are highly correlated. Venom composition in terminal clades and taxa were better explained by protein losses than evolution of new proteins. The triseriatus group share seven proteins, while the clade C. aquilus + C. triseriatus share seven derived protein features, of which six are protein losses.
Parasitoidism is a trophic strategy that has evolved repeatedly in insects, but it has reached its greatest diversification and mechanistic sophistication in Hymenoptera. The ecological success of parasitoid wasps is strongly linked to their capacity to regulate host physiology through a temporally coordinated and compartmentalised arsenal of maternal and embryonic factors. Maternal components, including venom, calyx fluid and polydnaviruses, are delivered during oviposition, whereas embryonic factors, such as teratocytes and larval secretions, act throughout larval development within the host. Together, this diverse toolkit of molecular effectors manipulates host immunity, endocrine signalling, metabolism, development and behaviour, thereby ensuring survival of parasitoid larvae. This review first examines parasitoidism as an evolutionary and ecological strategy, highlighting diverse strategies of host exploitation. We then examine the principal molecular tools involved in host regulation and their mechanistic roles in host-parasitoid interactions. Finally, we critically evaluate the biotechnological potential of these molecules, with an emphasis on proteins and peptides that may serve as templates for peptide engineering, recombinant technologies and bioinspired molecular development, especially for insecticides and antimicrobials.
Mast cells (MCs) are versatile, multifunctional immune cells with broad roles in physiological homeostasis and pathogenic processes. MCs are found in most tissues, including skin, lungs, intestines, and peritoneum, and they vary in numbers, types, and biological functions. MCs are implicated in host defense against various pathogens, including bacteria, viruses, and fungi. Additionally, MCs are crucial in protecting against toxins, including those present in venoms from multiple species, such as honeybees, snakes, scorpions, and lizards. Although MCs play an essential role in host defense, they are mostly known for their detrimental actions in allergic reactions, such as asthma, food allergy, anaphylaxis, mastocytosis, and various inflammatory skin conditions. Under such conditions, MCs are activated (via IgE-mediated or other mechanisms) and release a range of potent proinflammatory mediators, including tumor necrosis factor α. In addition to cytokines, they are major producers of histamine and various proteases, including chymase, tryptase, and carboxypeptidase A3. As a result, these mediators contribute to the pathological manifestations associated with inflammatory conditions and other disorders. This review focuses mainly on the biological role of MCs and their proteases, with a focus on chymase and tryptase, as well as their inhibitors as candidate therapies for MC-driven diseases. SIGNIFICANCE STATEMENT: Mast cells (MCs) and their proteases are central regulators of tissue homeostasis, barrier defense, and inflammation across multiple organs, but are also associated with numerous diseases. Ongoing research has shown that the function of MCs is highly dependent on their tissue location, where the local tissue environment shapes their phenotype, protease expression, and, consequently, their biological functions. However, further investigation is required to more precisely understand the physiological conditions governing the transition of MCs from maintaining tissue homeostasis to acquiring pathogenic functions, particularly with respect to their protease-dependent activities. By profiling MC heterogeneity using multiomics approaches to map protease-driven signaling networks, it will be possible to gain deeper insight into their functional roles and establish a conceptual framework to guide the development of next-generation, mechanism-based therapeutics that selectively modulate MC activity in human diseases.
Aquatic envenomations may cause severe tissue injury, neurologic morbidity, and even mortality among those whose leisure and/or occupational activities expose them to marine and freshwater animals. The Motoro ray, or Potamotrygon motoro (also known as an ocellate river stingray) is endemic to freshwater tributaries throughout Brazil, and is a frequent source of severe envenoming of local fisherman and those residing near waterways. Local wound management including immersion in warm water, wound cleaning and debridement, as well as antibiotics are mainstays of treatment, as are local anesthetics (e.g., nerve blocks) and systemic opioid analgesics; however, high-quality evidence supporting such interventions is lacking. We present a case of a Canadian who was envenomed by his pet Motoro ray, and describe his clinical presentation and evolution of symptoms over the subsequent months. With the ever-increasing trade of exotic wildlife, clinicians, public health authorities, and those within the broader wildlife regulatory ecosystem should be attuned for unanticipated adverse consequences, such as those described herein. We further situate this case within the existing published literature around this particular species of ray, which is not typically considered an ornamental fish.