Search Results (650)

The white-spotted jellyfish, Phyllorhiza punctata, is an invasive species with significant ecological and economic relevance spreading across various regions. While its ecological impact is well-documented, its molecular and biochemical characteristics remain poorly understood. In this study, we integrate proteomic data generated by LC-MS/MS with publicly available transcriptomic information to characterize P. punctata, analyzing differential protein expression across three distinct tissues: oral arms, mantle, and gonads. A total of 2764 proteins and 25,045 peptides were identified, including several venom components such as jellyfish toxins (JFTs) and phospholipase A2 (PLA2), which were further investigated and compared to toxins from other species. Enrichment analyses revealed clear tissue-specific functions. Additionally, deep learning and machine learning tools identified 274 promising AMP candidates, including the α-helical, β-sheet, and αβ-motif peptides. This dataset provides new insights into the protein composition of P. punctata and highlights strong AMP candidates for further characterization, underscoring the biotechnological potential of underexplored cnidarian species. Full article

This study used all-atom molecular dynamics simulations to investigate the structural dynamics of Ves a 1, a phospholipase from Vespa affinis venom, and its interactions within a lipid membrane environment, both alone and in the presence of the inhibitor voxilaprevir. Simulations conducted over 1 $\mathsf{\mu }$s for triplicate runs demonstrated system stability and convergence of structural properties. Our findings reveal that Ves a 1 engages in dynamic interactions with the lipid bilayer, involving key regions such as its lids, catalytic triad, and auxiliary site. The presence of voxilaprevir was observed to subtly alter these membrane interaction patterns and influence the enzyme’s catalytic area, reflecting the inhibitor’s impact within its physiological context. These results emphasize the crucial role of the lipid bilayer in shaping enzyme function and highlight voxilaprevir as a promising candidate for further inhibitor development, offering vital insights for rational drug design targeting membrane-associated proteins. Full article

Parasitoid venom significantly influences host physiology and development. Our previous research identified high levels of insulin-binding protein IMP-L2 in the venom of Scleroderma guani. IMP-L2 may inhibit the insulin/insulin-like growth factor signaling (IIS) cascade by competitively binding insulin-like peptides (ILPs) with insulin receptor (InR). However, how to regulate IIS transduction is unclear. We speculate that venom-derived IMP-L2 may bind ILPs to inhibit IIS transduction. Consequently, we investigated the regulation of the IIS/TOR pathway by venom-derived IMP-L2. An expression analysis of IIS/TOR pathway genes across various developmental stages of Tenebrio molitor demonstrated that this pathway governs the entire developmental process. By examining gene expression before and after parasitism, we determined that S. guani predominantly inhibits TOR pathway signaling in T. molitor post-parasitism. Bioinformatics and expression analyses revealed that IMP-L2 is critically involved in Hymenoptera insects, exhibiting high expression in the venom apparatus, and is upregulated in response to S. guani parasitism factors. Additionally, recombinant IMP-L2 was produced via eukaryotic expression. Finally, the recombinant IMP-L2 was found to inhibit the TOR and IIS/TOR signaling pathways at early (6 h) and late (24 h) stages post-injection. Knockdown of IMP-L2 in S. guani parasitized T. molitor pupae, resulting in accelerated death of T. molitor. During parasitism, S. guani may suppress host growth and development by modulating the IIS/TOR signaling pathway through venom-derived IMP-L2, potentially affecting host lifespan. Full article

Temporal lobe epilepsy (TLE) is a common drug-resistant form of epilepsy, often accompanied by cognitive and emotional disturbances, highlighting the urgent need for novel therapies. Scorpion Venom Heat-Resistant Synthetic Peptide (SVHRSP), isolated and synthetically derived from scorpion venom, has shown anti-epileptic and neuroprotective potential. This study evaluated the anti-epileptic effects of SVHRSP in a kainic acid (KA)-induced TLE rat model. Our results demonstrated that SVHRSP (0.81 mg/kg/day) reduced the frequency and severity of spontaneous seizures. Behavioral tests showed improved cognitive performance in the novel object recognition, object location, and T-maze tasks, as well as reduced anxiety-like behavior in the open-field test. Moreover, SVHRSP mitigated hippocampal neuronal loss and glial activation. Transcriptomic analysis indicated that SVHRSP upregulates genes involved in adhesion molecule-triggered and axon guidance pathways. Western blotting and immunofluorescence further confirmed that SVHRSP restored dendritic (MAP2), axonal (NFL), and synaptic (PSD95) marker expression, elevated the functionally important L1CAM fragment (L1-70), and increased myelin basic protein-induced serine protease activity responsible for L1-70 generation. Blockade of L1CAM expression diminished the neuroprotective effects of SVHRSP, suggesting a critical role for L1CAM-mediated synapse functions. This study is the first to reveal the therapeutic potential of SVHRSP in TLE via L1CAM-associated mechanisms. Full article

The composition of Australian snake venoms is the least well-known of any continent. We characterised the venom proteome of the southern death adder Acanthophis antarcticus—one of the world’s most morphologically and ecologically divergent elapids. Using a combined bottom-up proteomic and venom gland transcriptomic approach employing reverse-phase chromatographic and gel electrophoretic fractionation strategies in the bottom-up proteomic workflow, we characterised 92.8% of the venom, comprising twelve different toxin identification hits belonging to seven toxin families. The most abundant protein family was three-finger toxins (3FTxs; 59.8% whole venom), consisting mostly of one long-chain neurotoxin, alpha-elapitoxin-Aa2b making up 59% of the venom and two proteoforms of another long-chain neurotoxin. Phospholipase A₂s (PLA₂s) were the second most abundant, with four different toxins making up 22.5% of the venom. One toxin was similar to two previous non-neurotoxic PLA₂s, making up 16% of the venom. The remaining protein families present were CTL (3.6%), NGF (2.5%), CRiSP (1.8%), LAAO (1.4%), and AChE (0.8%). A. antarcticus is the first Australian elapid characterised that has a 3FTx dominant venom, a composition typical of elapids on other continents, particularly cobras Naja sp. The fact that A. antarcticus has a venom composition similar to cobra venom while having a viper-like ecology illustrates that similar venom expressions can evolve independently of ecology. The predominance of post-synaptic neurotoxins (3FTxs) and pre-synaptic neurotoxins (PLA₂) is consistent with the neurotoxic clinical effects of envenomation in humans. Full article

Background. The venom of Loxoscelesrufescens (L.r.), also known as the violin and/or brown spider, contains a wide variety of proteins and can induce a complex, intense, and uncontrolled inflammatory response, hemolysis, thrombocytopenia, dermo-necrosis, and renal failure. Studies have postulated the efficacy of hyperbaric oxygen therapy (HBOT) for Loxosceles bites. However, data describing the use and beneficial effects of HBO are, to date, relatively scarce. Only a few cases of Loxosceles bites in Northern Italy have been documented, and there is no laboratory test available for the diagnosis. Objectives. We present seven cases (aged 54.5 ± 4.2 years) of patients who presented to the emergency room (E.R.) of Niguarda Hospital in Milan from March to October 2022. Methods. Blood and urine samples were collected and biomarkers of oxidative stress (OxS) (reactive oxygen species (ROS), total antioxidant capacity (TAC), lipid peroxidation (8iso-PFG2α), DNA damage (8-OH-dG)), inflammation (IL-6, IL-1β, TNF-α, sICAM1), and renal function (creatinine, neopterin, uric acid) before (T0), during (T1, T2), and after (1–2 wk T3–T4; 1 month T5) the HBOT treatment (US Navy Treatment Table 15 protocol) were studied. Results. At T0, patients showed a significant unbalance of OxS; high levels of ROS, 8-isoPGF2α, and inflammatory status (IL-6, TNF-α; sICAM); and a low level of antioxidant capacity. At the end of HBOT (T2), a significant reduction in Oxy-inflammation levels over time—8-iso −26%, 8-OH-dG −9%, IL-6 −71%, IL-1bβ −12%, TNF-α −13%, and sICAM1 −17%—associated with clinical improvement was shown. Conclusions. These reductions, along with those in renal function markers, mirrored the observed improvement in the evolution of the skin lesion and the patients’ self-reported general wellness and pain. In conclusion, HBOT should be considered a valuable therapeutic tool after L.r. bites. Full article

The Steinernema carpocapsae nematode is known to release several excretory/secretory products (ESPs) in its venom upon contact and during the parasitic infection process of insect hosts. A recurrent family of proteins found in this nematode’s venom is the CAP (cysteine-rich secretory protein/antigen 5/pathogenesis-related 1) protein, but the functional role of these proteins remains unknown. To elucidate the biological function, this study focused on characterising the secreted protein, first identified in the venom of the nematode’s parasitic stage, and the sequence retrieved from transcriptomic analysis. The structural comparisons of the Sc-CAP protein model, as determined by AlphaFold2, revealed related structures from other parasitic nematodes of vertebrates. Some of these closely related proteins are reported to have sterol-binding ability. The Sc-CAP recombinant protein was successfully produced in Escherichia coli in conjunction with a chaperone protein. The results showed that the Sc-CAP protein binds to cholesterol, and docking analyses of sterols on the protein revealed potential molecular interactions. Immunoassays performed in Galleria mellonella larvae revealed that this venom protein has an inhibitory effect against phenoloxidase and the antimicrobial response of insects. This suggests that the venom protein has an immunomodulatory function against insects, emphasising its importance during the parasite–host interaction. Full article

Background: Snake envenomation is a major public health issue in Nigeria, primarily due to bites from Echis ocellatus, Naja nigricollis, and Bitis arietans. Understanding their venom composition is essential for effective antivenom development. This study characterizes and compares the venom proteomes of these snakes using iTRAQ-based proteomics, focusing on key toxin families and their relative abundances. Methods: Venom samples were ethically collected from adult snakes, pooled by species, lyophilized, and stored for proteomic analysis. Proteins were extracted, digested with trypsin, and labeled with iTRAQ. Peptides were analyzed via mass spectrometry, and data were processed using Mascot and IQuant for protein identification and quantification. Results: E. ocellatus and B. arietans venoms had similar profiles, rich in C-type lectins, serine proteases, and phospholipase A₂s. These comprised 17%, 11%, and 5% in E. ocellatus and 47%, 10%, and 7% in B. arietans, with metalloproteinases dominating both (53% and 47%). In N. nigricollis, three-finger toxins (9%) were most abundant, followed by metalloproteinases (3%). All species shared four core protein families, with N. nigricollis also containing four uncharacterized proteins. Conclusions: This study highlights venom compositional differences, advancing snake venom biology and informing targeted antivenom development. Full article

For centuries, researchers have been fascinated by the composition of scorpion venom and its local and systemic effects on humans. During a sting, scorpions inject peptides and proteins that can affect immune cells and neurons. While the immune and nervous systems have been studied independently in the context of scorpion stings, here we reveal part of the mechanism by which Tityus serrulatus venom induces hyperalgesia in mice. Through behavioral, immune, imaging assays, and mice genetics, we demonstrate evidence of neuroimmune crosstalk during scorpion stings. Tityus serrulatus venom induced mechanical and thermal hyperalgesia in a dose-dependent manner, as well as overt pain-like behavior. The venom directly activated dorsal root ganglia neurons and increased the recruitment of macrophages and neutrophils, releasing pro-inflammatory cytokines TNF-α and IL-1β. Blocking TRPV1⁺ neurons, TNF-α, IL-1β, and NFκB reduced the mechanical and thermal hyperalgesia, overt pain-like behavior, and the migration of macrophages and neutrophils induced by Tityus serrulatus venom. Collectively, Tityus serrulatus venom targets primary afferent nociceptive TRPV1⁺ neurons to induce hyperalgesia through the recruitment of macrophages and neutrophils and the release of pro-inflammatory cytokines. Full article

The venom of Nemopilema nomurai jellyfish represents a promising source of bioactive compounds with potential pharmacological applications. In our previous work, we identified two novel angiotensin-converting enzyme (ACE)-inhibitory peptides—IVGRPLANG (896.48 Da) and IGDEPRHQYL (1227.65 Da)—isolated from N. nomurai venom hydrolysates via papain digestion. In this study, we conducted a detailed biochemical and computational characterization of these peptides. The IC₅₀ values were determined to be 23.81 µM for IVGRPLANG and 5.68 µM for IGDEPRHQYL. Kinetic analysis using Lineweaver–Burk plots revealed that both peptides act as competitive ACE inhibitors, with calculated inhibition constants (K_i) of 51.38 µM and 5.45 µM, respectively. To assess the structural stability of the ACE–peptide complexes, molecular dynamics simulations were performed. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses provided insights into complex stability, while interaction fraction analysis elucidated key bond types and residue–ligand contacts involved in binding. Furthermore, a network pharmacology approach was employed to predict therapeutic targets within the renin–angiotensin–aldosterone system (RAAS). Eleven target proteins were identified: IVGRPLANG was associated with REN, ACE, CTSB, CTSS, and AGTR2; IGDEPRHQYL was linked to REN, AGT, AGTR1, AGTR2, KNG1, and BDKR2. Molecular docking analyses using HADDOCK software (version 2.4) were conducted for all targets to evaluate binding affinities, providing further insight into the peptides’ therapeutic potential. Full article

An experimental model of acute pulmonary damage was developed based on the intravenous injection of the phospholipase A₂ (PLA₂)-rich venom of Pseudechis papuanus (Papuan black snake) in mice. Venom caused pulmonary edema, with the accumulation of a protein-rich exudate, as observed histologically and by analysis of bronchoalveolar lavage fluid (BALF). In parallel, venom induced an increase in all of the pulmonary mechanical parameters evaluated, without causing major effects in terms of tracheal and bronchial reactivity. These effects were abrogated by incubating the venom with the PLA₂ inhibitor varespladib, indicating that this hydrolytic enzyme is responsible for these alterations. The venom was cytotoxic to endothelial cells in culture, hydrolyzed phospholipids of a pulmonary surfactant, and reduced the activity of angiotensin-converting enzyme in the lungs. The pretreatment of mice with the nitric oxide synthase inhibitor L-NAME reduced the protein concentration in the BALF, whereas no effect was observed when mice were pretreated with inhibitors of cyclooxygenase (COX), tumor necrosis factor-α (TNF-α), bradykinin, or neutrophils. Based on these findings, it is proposed that the rapid pathological effect of this venom in the lungs is mediated by (a) the direct cytotoxicity of venom PLA₂ on cells of the capillary–alveolar barrier, (b) the degradation of surfactant factor by PLA₂, (c) the deleterious action of nitric oxide in pulmonary tissue, and (d) the cytotoxic action of free hemoglobin that accumulates in the lungs as a consequence of venom-induced intravascular hemolysis. Our findings offer clues on the mechanisms of pathophysiological alterations induced by PLA₂s in a variety of pulmonary diseases, including acute respiratory distress syndrome (ARDS). Full article

Cone snails are a large group of marine gastropods that produce a complex mixture of toxic compounds to hunt prey and defend against predators. The majority of the venom comprises small toxic peptides named conotoxins, which target membrane receptors. In contrast, a smaller part of the venom contains larger proteins and conoproteins, which are thought to be involved in conotoxin maturation and the envenomation process, respectively. Interestingly, many species of cone snails contain conoporins, which are similar to actinoporins—pore-forming toxins found in sea anemones. These actinoporin-like proteins (ALPs) have recently been detected in many molluscan species, and only a few have been experimentally characterized. Due to being highly expressed in the venom gland of many cone snail species, conoporins are thought to play an important part in the envenomation process. Despite this, the exact function of conoporins is currently unknown. We propose several hypotheses aiming to elucidate their biological role. Full article

Honey and other bee products, including propolis, royal jelly, and bee pollen, are widely recognized for their medicinal properties. Among their numerous biological activities, their anti-inflammatory and immunomodulatory effects have gained significant attention in recent years. Immune and inflammatory disorders contribute significantly to the development of chronic conditions, including cancer and diabetes. Bee-derived products, along with their bioactive compounds such as polyphenols, have shown promising therapeutic effects in modulating inflammatory mediators. Studies indicate that these products help regulate tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and interleukin-7 (IL-7) levels while reducing reactive oxygen species (ROS) production. Additionally, both in vitro and in vivo research, along with clinical studies, highlight their role in enhancing immune responses by activating B and T lymphocytes. This review explores the molecular mechanisms underlying these properties, emphasizing the role of bioactive compounds such as flavonoids, phenolic acids, and proteins in modulating immune responses and reducing inflammation. Evidence from in vitro, in vivo, and clinical studies suggests that honey and bee products influence cytokine production, regulate immune cell activity, and mitigate oxidative stress, making them potential therapeutic agents for inflammatory and immune-related disorders. To gather relevant information, databases such as Google Scholar, PubMed, and ScienceDirect were searched using various keyword combinations, including immunomodulatory, anti-inflammatory, bee products, honey, propolis, royal jelly, bee venom, and bee pollen. Given their anti-inflammatory, immune-protective, antioxidant, anti-apoptotic, and antimicrobial properties, bee products remain a subject of interest for further clinical evaluation. Full article

Snakebite is a high-priority neglected tropical disease, and a strategic goal based on four pillars has been recommended to reduce mortality and morbidity. One is empowering rural communities through citizen science, education, and engagement. In this study, an integrative approach was used to expand our knowledge of Micrurus nigrocinctus status and characterize its venom. Using citizen science data and field visits to local communities, 99 records of M. nigrocinctus distributed in Antioquia, Chocó, and Córdoba were obtained. Children, young people, and adults recognized M. nigrocinctus as the most common coral snake species in their region, and two specimens were recovered for venomic and Phylogenetic analyses. The M. nigrocinctus venom from Colombia exhibited similar chromatographic and electrophoretic profiles and biological activities and shared nearly identical protein families with Costa Rica. Commercial coral snake antivenoms also recognized and neutralized the whole venom from both countries. However, phylogenetic relationships showed greater divergence with specimens from Costa Rica. Involving communities helps prevent coral snake bites and facilitates access to rare specimens such as M. nigrocinctus, thereby enabling venom analyses, improving antivenom evaluation, and advancing toxinology research for medically significant species. Full article

Snake venoms contain numerous toxic proteins, but low-abundance proteins often remain uncharacterized due to identification challenges. This study employs a bioinformatics approach to identify and structurally model low-abundance proteins from the venom gland transcriptomes of Bothrops asper and Bothrops jararaca. Using tools such as tblastn, Jalview, and CHIMERA, we analyzed sequences and structural features of proteins including arylsulfatase, CRISP (Cysteine-Rich Secretory Protein), von Willebrand factor type D (vWFD), and dihydroorotate dehydrogenase (DHODH), and identified potential new isoforms of SVMP-PIIIb (Ba_1) and botrocetin in B. asper. Protein models were generated with AlphaFold2, compared with crystallized structures from the Protein Data Bank (PDB), and validated using Procheck, ERRAT, and Verify3D. Conserved motifs and domains were annotated through Pfam and InterPro, revealing structural elements that suggest possible roles in venom physiology and toxicity. These findings emphasize the potential of computational biology to characterize structurally relevant but experimentally inaccessible venom proteins, and to lay the groundwork for future functional validation. Full article