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.
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.
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.
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.
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.
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.
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.
Scorpion venom peptides, with their stable disulfide backbone, compact structural framework, and highly selective regulation of ion channels, have long been regarded as important molecular probes in neuropharmacology. However, recent studies have revealed their potential for regulating oxidative stress, inflammation, and neuroprotection, making them a new research frontier. In this article, we focus on scorpion venom peptides as drugs, constructing an integrated knowledge framework from structural classification to clinical translation. First, scorpion venom peptides are systematically classified based on cysteine arrangement patterns and three-dimensional folding topology, and their structure-activity relationships are summarized. Based on this, the molecular mechanisms by which scorpion venom peptides regulate ion channels are systematically analyzed. We review the emerging pharmacological activities of scorpion venom peptides. Of particular note, the representative molecule SVHRSP has shown multi-target synergistic antioxidant and neuroprotective activity in models of Parkinson's disease. We also systematically evaluate the application of engineering strategies, including cyclisation modification, nanodelivery, recombinant expression, and AI-assisted optimization, to overcome the translational bottlenecks in the development of scorpion venom peptides. However, it should be noted that most SVHRSP-related findings have been reported by a single research group; independent replication, pharmacokinetic characterization, and human efficacy data are still lacking. Its IND approval permits clinical investigation but does not yet constitute proven therapeutic benefit in patients. By integrating molecular structure, redox regulation mechanisms, and translational medicine perspectives, this review aims at providing a theoretical basis and practical pathways for scorpion venom peptides as precision therapeutic molecules for oxidative stress-related diseases.
The study evaluated bone repair in tibial defects of Wistar rats treated with 45S5 bioactive glass, either alone or combined with lyophilized heterologous fibrin biopolymer (HFB) and/or photobiomodulation therapy (PBM). Thirty-five animals were randomly assigned to five groups: control (CG), Bioactive glass (BG), Bioactive glass + HFB (BFG), Bioactive glass + PBM (BPG), and Bioactive glass + HFB + PBM (BFPG). After 42 days, the samples were analyzed by micro-computed tomography, histology (Hematoxylin-Eosin, Masson's Trichrome, and Picrosirius Red), and histomorphometry. Histological and micro-CT findings demonstrated improved defect closure and better matrix organization in the BG and BFG groups. Histomorphometric analysis revealed significant differences among the groups (ANOVA, p < 0.0001), with the BG group showing the highest percentage of new bone formation (40.35 ± 4.14%), significantly higher than the BPG and BFPG groups. The addition of HFB did not impair bone repair and yielded intermediate results, whereas PBM did not demonstrate a positive effect on bone regeneration at the 42-day time point under the parameters used in this study. It can be concluded that bioactive glass, especially when used alone or in combination with heterologous fibrin biopolymer, promoted superior bone regeneration, while its association with photobiomodulation did not demonstrate additional benefit at 42 days.
Stingray envenomation is a relatively common occurrence among water sports enthusiasts, including swimmers, scuba divers, and surfers, as well as among fishermen. However, there is a lack of medical literature on the pathophysiology of immediate and delayed hypersensitivity reactions and, more importantly, on the range of bacterial and mycobacterial infections that can result from these envenomation injuries. This paper aims to provide a general overview of the mechanisms, diagnostic challenges, and management of late hypersensitivity reactions and infections that can occur following stingray stings. A 63-year-old man with well-controlled hyperlipidemia presented to the Mayo Clinic with a 1-week-old injury from accidentally stepping on a stingray barb while walking on a beach in Ventura, California. Immediate pain was relieved with immersion in warm water. He did not take any over-the-counter or prescription medications, and over the following days, he returned to his usual activities of cycling, running, and swimming with minimal discomfort. There was no initial redness or swelling at the puncture site, but he reported intermittent sharp, localized pain with movement leading up to his hospital visit. A biopsy was performed due to concern for a developing necrotic infection, and he was diagnosed with a hypersensitivity reaction. He was initially treated with intravenous antibiotics, and steroids were added based on biopsy results. After completing his treatment course, his hypersensitivity reaction fully resolved over several weeks. This case underscores the importance of considering both immediate and delayed hypersensitivity reactions that can result from stingray envenomation. These reactions can be managed with conservative measures, such as warming the affected area in a water bath to denature heat-labile venom, as well as with conventional therapies, including topical or systemic antihistamines and steroids. It also highlights the need for early empiric antibiotic coverage and outlines the infectious agents implicated in early- and late-onset infections following stingray envenomation, including Pseudomonas aeruginosa, Vibrio vulnificus, and Mycobacterium fortuitum. Additionally, it emphasizes the need for tetanus vaccine updates, radiography, and a multidisciplinary approach to treating stingray injuries.
Melittin (Mel) is a membrane-active peptide with potential anticancer activity, but its direct therapeutic application may be limited by nonspecific toxicity and delivery-related challenges. The study aimed to assess melittin-functionalized magnetic nanoparticles (MNPs-Mel) as a strategy to enhance antitumor activity in Caco-2 cells, with/without magnetic hyperthermia (MH) association. BJ fibroblasts were used as a normal human in vitro cellular model. The effects of free Mel (2.5 µg/mL), MNPs, and MNPs-Mel (50 µg/mL both) + MH (30 min at 355 kHz and 25 kA/m) were assessed using colorimetry (for viability), luminescence (ATP), and spectrophotometry (lactate) following different exposure conditions. The mechanism of apoptosis induction was evaluated by ELISA (caspase 8 and 9 levels). Transmission electron microscopy (TEM) was also used to evaluate nanoparticle morphology and treatment-associated cellular ultrastructural changes. Free Mel reduced viability in both cell lines, with Caco-2 cells showing greater sensitivity at lower concentrations. MNPs (with/without MH) produced limited and less consistent effects, whereas MNPs-Mel significantly reduced Caco-2 viability and ATP levels and increased LDH and caspase 9. MH further enhanced the effects of MNPs-Mel: reduced viability (57-58% of the control at 24 h and 72 h), decreased ATP levels (67% of the control at 24 h and 53% at 72 h), increased LDH levels (206% of the control at 24 h and 301% at 72 h), and induced the mitochondrial apoptotic pathway (caspase 9 increased with 2164% of the control at 72 h). TEM proved the internalization of both MNPs and MNPs-Mel and revealed extensive ultrastructural alterations concerning mitochondria and lysosomes produced by MNPs-Mel, particularly in the Caco-2 cells. These modifications were heavily increased by MNPs-Mel + MH exposure. Overall, these findings demonstrate that Mel functionalization increases the antitumor activity of Mel at lower doses and that MH further potentiates this effect in Caco-2 cells.
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.
Snakebite envenomation is a global public health concern, and hemotoxic bites can lead to severe coagulopathy, microangiopathic hemolytic anemia, and compartment syndrome. We describe a previously healthy 6-year-old boy who presented with progressive left lower limb swelling, discoloration, and bleeding from intravenous cannula sites following a snakebite sustained in rural Pakistan, consistent with severe hemotoxic envenomation. Despite antivenom and transfusion support, he developed persistent venom-induced consumption coagulopathy with hypofibrinogenemia, markedly prolonged clotting times, thrombocytopenia, and features of microangiopathic hemolytic anemia. Severe limb swelling raised concern for compartment syndrome; however, fasciotomy was deferred due to the high risk of bleeding in the setting of uncontrolled coagulopathy. Transferred to Bahrain, he underwent five sessions of therapeutic plasma exchange, initiated due to ongoing clinical and laboratory deterioration, resulting in stabilization of hematologic parameters, resolution of limb swelling, and preservation of limb function. This case highlights the role of plasma exchange in children unresponsive to conventional therapy and demonstrates that conservative management of suspected compartment syndrome may be feasible when surgical intervention carries significant risk, underscoring the importance of early recognition and multidisciplinary care in complex pediatric envenomation.
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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.
The growth-inhibiting effect of the peptide Uy234, present in the venom of the scorpion Urodacus yaschenkoi, has been investigated in two bacterial pathogens: Staphylococcus aureus ATCC 25923 and Acinetobacter baumannii AE12, the latter being a multidrug-resistant clinical isolate. With the aim of determining the possible role of specific residues in the bioactivity of this peptide, we studied a proline residue at position 9 and the C-terminal amidation of this peptide. Two inactivated variants were analyzed: Uy234-C, a non-amidated peptide, and Uy234-A, a P9A mutant. In addition to quantifying in detail the minimum inhibitory and bactericidal concentrations for each microorganism, membrane-damaging effects were assessed through bacterial cell viability assays with SYTO9/PI fluorophores. In addition, AFM, electroforming, and GUV microaspiration were used to determine the effects of each peptide in terms of permeabilization. Molecular dynamics (MD) simulations were also performed for the wild-type peptide and its P9A mutant. Only the native peptide Uy234 showed bacteriostatic and bactericidal activity, whereas the P9A mutant and non-amidated variant lost antimicrobial activity, demonstrating the essential role of the Pro-9 residue and C-terminal amidation in Uy234 bioactivity against both pathogens. SYTO9/PI assays in S. aureus infection showed membrane damage only with native Uy234, while AFM and GUV studies revealed membrane thinning, lateral expansion, and dose-dependent permeabilization of lipid bilayers. Our study provides clear evidence of a damaging effect on the membrane associated with the bioactivity of Uy234. This bioactivity is directly associated with the presence of residue P9 and the presence of C-terminal carboxyamidation. The mutant peptide P9A is unable to permeabilize GUVs, which is consistent with the persistence of a greater degree of structural order, according to MD simulations in the aqueous phase. This study provides a framework for the rational design of bactericidal peptides targeting multidrug-resistant bacteria.
Urticating setae in the corethrogyne of female moths of Notodontidae (Anaphinae and Thaumetopoeinae) from Africa, Asia, and Australia were compared using light and scanning electron microscopy. In all 14 species examined, the proximal tip of the setae was spear-shaped with a lateral opening and had lobed or serrated barbs. Notable variation among genera was observed at the distal end of the seta, characterized by 5 non-exclusive forms: tapered (genera Adrallia Walker, Anaphe Walker, Hypsoides Butler, Paradrallia Bethune-Baker, and Tanystola Turner), spatulate (genera Adrallia, Epanaphe Aurivillius, Epicoma Hübner, Hypsoides, and Trichiocercus Stephens), blunt (genus Paradrallia), cup-shaped (genus Ochrogaster Herrich-Schäffer), or hook-shaped (genus Gazalina Walker). Verrucose projections on the distal end of the seta were present in 4 genera of Anaphinae (Adrallia, Anaphe, Epanaphe, and Hypsoides) and in 1 genus of Thaumetopoeinae (Epicoma), and their functional significance is discussed. Phylogenetic analyses of the cytochrome c oxidase subunit I gene region provided a framework for comparing setal morphology and geographic distribution among genera. This study is the first to compare and describe the morphology of urticating setae across females of multiple notodontid species. The shared setal morphologies, which appear to enhance aerodynamics and facilitate toxin dispersal, indicate that notodontid moths have evolved highly effective defense strategies and protection of their egg mass.
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.
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.