-
Molecules (Basel, Switzerland) Feb 2024Sol g 2 is the major protein in fire ant venom. It shares the highest sequence identity with Sol i 2 () and shares high structural homology with LmaPBP...
Sol g 2 is the major protein in fire ant venom. It shares the highest sequence identity with Sol i 2 () and shares high structural homology with LmaPBP (pheromone-binding protein (PBP) from the cockroach ). We examined the specific Sol g 2 protein ligands from fire ant venom. The results revealed that the protein naturally formed complexes with hydrocarbons, including decane, undecane, dodecane, and tridecane, in aqueous venom solutions. Decane showed the highest affinity binding (K) with the recombinant Sol g 2.1 protein (rSol g 2.1). Surprisingly, the mixture of alkanes exhibited a higher binding affinity with the rSol g 2.1 protein compared to a single one, which is related to molecular docking simulations, revealing allosteric binding sites in the Sol g 2.1 protein model. In the trail-following bioassay, we observed that a mixture of the protein sol g 2.1 and hydrocarbons elicited worker ants to follow trails for a longer time and distance compared to a mixture containing only hydrocarbons. This suggests that Sol g 2.1 protein may delay the evaporation of the hydrocarbons. Interestingly, the piperidine alkaloids extracted have the highest attraction to the ants. Therefore, the mixture of hydrocarbons and piperidines had a synergistic effect on the trail-following of ants when both were added to the protein.
Topics: Animals; Carrier Proteins; Fire Ants; Pheromones; Ligands; Molecular Docking Simulation; Ants; Alkanes; Ant Venoms
PubMed: 38474545
DOI: 10.3390/molecules29051033 -
Scientific Reports Mar 2024Enterotoxins are a type of toxins that primarily affect the intestines. Understanding their harmful effects is essential for food safety and medical research. Current...
Enterotoxins are a type of toxins that primarily affect the intestines. Understanding their harmful effects is essential for food safety and medical research. Current methods lack high-throughput, robust, and translatable models capable of characterizing toxin-specific epithelial damage. Pressing concerns regarding enterotoxin contamination of foods and emerging interest in clinical applications of enterotoxins emphasize the need for new platforms. Here, we demonstrate how Caco-2 tubules can be used to study the effect of enterotoxins on the human intestinal epithelium, reflecting toxins' distinct pathogenic mechanisms. After exposure of the model to toxins nigericin, ochratoxin A, patulin and melittin, we observed dose-dependent reductions in barrier permeability as measured by TEER, which were detected with higher sensitivity than previous studies using conventional models. Combination of LDH release assays and DRAQ7 staining allowed comprehensive evaluation of toxin cytotoxicity, which was only observed after exposure to melittin and ochratoxin A. Furthermore, the study of actin cytoskeleton allowed to assess toxin-induced changes in cell morphology, which were only caused by nigericin. Altogether, our study highlights the potential of our Caco-2 tubular model in becoming a multi-parametric and high-throughput tool to bridge the gap between current enterotoxin research and translatable in vivo models of the human intestinal epithelium.
Topics: Humans; Enterotoxins; Bacterial Toxins; Caco-2 Cells; Melitten; Nigericin; Intestinal Mucosa
PubMed: 38461178
DOI: 10.1038/s41598-024-56520-5 -
Nature Computational Science Mar 2024
Topics: Animals; Scorpions; Gene Regulatory Networks; Sequence Analysis, DNA; Scorpion Venoms
PubMed: 38459274
DOI: 10.1038/s43588-024-00615-6 -
European Journal of Medicinal Chemistry Mar 2024The emergence of bacterial resistance has posed a significant challenge to clinical antimicrobial treatment, rendering commonly used antibiotics ineffective. The... (Review)
Review
The emergence of bacterial resistance has posed a significant challenge to clinical antimicrobial treatment, rendering commonly used antibiotics ineffective. The development of novel antimicrobial agents and strategies is imperative for the treatment of resistant bacterial infections. Antimicrobial peptides (AMPs) are considered a promising class of antimicrobial agents due to their low propensity for resistance and broad-spectrum activity. Anoplin is a small linear α-helical natural antimicrobial peptide that was isolated from the venom of the solitary wasp Anplius samariensis. It exhibits rich biological activity, particularly broad-spectrum antimicrobial activity and low hemolytic activity. Over the past three decades, more than 40 research publications on anoplin have been made available online. This review focuses on the advancements of anoplin in antimicrobial research, encompassing its sources, characterization, antimicrobial activity, influencing factors and structural modifications. The aim is to provide assistances for the development of new antimicrobial agents that can combat bacterial resistance.
Topics: Humans; Antimicrobial Cationic Peptides; Anti-Infective Agents; Wasp Venoms; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Microbial Sensitivity Tests
PubMed: 38452726
DOI: 10.1016/j.ejmech.2024.116276 -
Iranian Biomedical Journal Jan 2024The potential anticancer effect of melittin has motivated scientists to find its exact molecular mechanism of action. There are few data on the effect of melittin on the...
BACKGROUND
The potential anticancer effect of melittin has motivated scientists to find its exact molecular mechanism of action. There are few data on the effect of melittin on the UPR and autophagy as two critical pathways involved in tumorigenesis of colorectal and drug resistance. This study aimed to investigate the effect of melittin on these pathways in the colorectal cancer (CRC) HCT116 cells.
METHODS
MTT method was carried out to assess the cytotoxicity of melittin on the HCT116 cell line for 24, 48, and 72 h. After selecting the optimal concentrations and treatment times, the gene expression of autophagy flux markers (LC3-βII and P62) and UPR markers (CHOP and XBP-1s) were determined using qRT-PCR. The protein level of autophagy initiation marker (Beclin1) was also determined by Western blotting.
RESULTS
MTT assay showed a cytotoxic effect of melittin on the HCT116 cells. The increase in LC3-βII and decrease in P62 mRNA expression levels, along with the elevation in the Beclin1 protein level, indicated the stimulatory role of melittin on the autophagy. Melittin also significantly enhanced the CHOP and XBP-1s expressions at mRNA level, suggesting the positive role of the melittin on the UPR activation.
CONCLUSION
This study shows that UPR and autophagy can potentially be considered as two key signaling pathways in tumorigenesis, which can be targeted by the BV melittin in the HCT116 cells. Further in vivo evaluations are recommended to verify the obtained results.
Topics: Humans; HCT116 Cells; Melitten; Beclin-1; Unfolded Protein Response; Autophagy; RNA, Messenger; Carcinogenesis; Colorectal Neoplasms
PubMed: 38445441
DOI: 10.61186/ibj.3993 -
Toxicology Mar 2024The present work aims to clarify the genotype differences of a model organism Saccharomyces cerevisiae in response to bee venom. The study evaluated various endpoints...
The present work aims to clarify the genotype differences of a model organism Saccharomyces cerevisiae in response to bee venom. The study evaluated various endpoints including cell survival, induction of physiologically active superoxide anions, mitotic gene conversion, mitotic crossing-over, reverse mutations, DNA double-strand breaks, and Ty1 retrotransposition. The role of the intact mitochondria and the YAP1 transcription factor was also evaluated. Our results indicate a genotype-specific response. The first experimental evidence has been provided that bee venom induces physiologically active superoxide anions and DNA double-strand breaks in S. cerevisiae. The lack of oxidative phosphorylation due to disrupted or missing mitochondrial DNA reduces but not diminishes the cytotoxicity of bee venom. The possible modes of action could be considered direct damage to membranes (cytotoxic effect) and indirect damage to DNA through oxidative stress (genotoxic effect). YAP1 transcription factor was not found to be directly involved in cell defense against bee venom treatment.
Topics: Bee Venoms; DNA; DNA Damage; Mitochondria; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Superoxides; Transcription Factors; Humans
PubMed: 38442839
DOI: 10.1016/j.tox.2024.153768 -
Dental and Medical Problems 2024Diabetes mellitus (DM) is a critical chronic metabolic disease. Several treatment modalities are currently under investigation. Both bee venom (BV) and bone marrow...
BACKGROUND
Diabetes mellitus (DM) is a critical chronic metabolic disease. Several treatment modalities are currently under investigation. Both bee venom (BV) and bone marrow mesenchymal stem cells (BMSCs) can possibly offer an approach for treating type I diabetes.
OBJECTIVES
The aim of the present study was to investigate the mechanism underlying the anti-diabetic effect of BV as compared to BMSCs on the tongue mucosa of diabetic rats.
MATERIAL AND METHODS
A total of 52 male albino rats were used in the current study. The rats were randomly assigned into 4 groups: group 1 (control); group 2 (streptozocin (STZ)); group 3 (BV-treated); and group 4 (BMSC-treated). Diabetes mellitus was induced via an intraperitoneal (IP) injection of STZ in the rats from groups 2, 3 and 4. Following the diagnosis of DM, the rats in group 3 were injected with a daily dose of 0.5 mg/kg of BV, while the rats in group 4 were treated with a single injection of BMSCs. All rats were euthanized after 4 weeks, and their tongues were dissected and divided into halves. The right halves of the tongues were utilized for the histological examination, followed by morphometric analysis. In contrast, the left halves were used to detect the local gene expression of transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF).
RESULTS
Group 2 revealed marked disruption in the morphology of the fungiform and filiform papillae, and atrophic epithelial changes in both dorsal and ventral surface epithelium as compared to other groups. Group 4 showed a significantly larger number of taste buds, and a higher gene expression of TGF-β1 and VEGF as compared to groups 2 and 3. Additionally, BV and BMSCs effectively increased the thickness of dorsal and ventral surface epithelium as compared to group 2.
CONCLUSIONS
Treatment with BMSCs was associated with significant improvement in the morphology and number of lingual epithelial cells and taste buds in the tongues of diabetic rats as compared to BV-treated rats, which was due to the local upregulation of TGF-β1 and VEGF gene expression.
Topics: Male; Animals; Rats; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A; Diabetes Mellitus, Experimental; Tongue; Mesenchymal Stem Cells; Bee Venoms
PubMed: 38441304
DOI: 10.17219/dmp/152924 -
Toxicon : Official Journal of the... Apr 2024Development of promising medicines from natural sources, specially venom, is of highly necessitated to combat against life-threatening cancers. Non-small cell lung...
BACKGROUND
Development of promising medicines from natural sources, specially venom, is of highly necessitated to combat against life-threatening cancers. Non-small cell lung cancer (NSCLC) has a significant percentage of mortalities. Melittin, from bee venom, is a potent anticancer peptide but its toxicity has limited its therapeutic applications. Accordingly, this study aims to synthesize niosomes with suitable stability and capacity for carrying melittin as a drug. Additionally, it seeks to evaluate the anti-cancer activity of melittin-loaded niosomes on non-small cell lung cancer.
METHODS
The niosome was prepared by thin film hydration method. Cytotoxicity and apoptosis were assessed on A549, Calu-3, and MRC5 cells. Real-time PCR was used to determine expression of apoptotic and pro-apoptotic Bax, Bcl2, and Casp3 genes. Immunocytochemistry (ICC) was also used to confirm expression of the abovementioned genes. Furthermore, wound healing assay was performed to compare inhibition effects of melittin-loaded niosomes with free melittin on migration of cancer cells.
RESULTS
IC50 values of melittin-loaded niosomes for A549, Calu-3, and MRC5 cells were respectively 0.69 μg/mL, 1.02 μg/mL, and 2.56 μg/mL after 72 h. Expression level of Bax and Casp3 increased '10 and 8' and '9 and 10.5' fold in A549 and Calu-3, whereas Bcl2 gene expression decreased 0.19 and 0.18 fold in the mentioned cell lines. The cell migration inhibited by melittin-loaded niosomes.
CONCLUSIONS
Melittin-loaded niosomes had more anti-cancer effects and less toxicity on normal cells than free melittin. Furthermore, it induced apoptosis and inhibited cancer cells migration. Our results showed that melittin-loaded niosomes may be a drug lead and it has the potential to be future developed for lung cancer treatment.
Topics: Humans; Melitten; Carcinoma, Non-Small-Cell Lung; Liposomes; Caspase 3; bcl-2-Associated X Protein; Lung Neoplasms
PubMed: 38432612
DOI: 10.1016/j.toxicon.2024.107673 -
Scientific Reports Feb 2024The toxin AaH-II, from the scorpion Androctonus australis Hector venom, is a 64 amino acid peptide that targets voltage-gated Na channels (VGNCs) and slows their...
The toxin AaH-II, from the scorpion Androctonus australis Hector venom, is a 64 amino acid peptide that targets voltage-gated Na channels (VGNCs) and slows their inactivation. While at macroscopic cellular level AaH-II prolongs the action potential (AP), a functional analysis of the effect of the toxin in the axon initial segment (AIS), where VGNCs are highly expressed, was never performed so far. Here, we report an original analysis of the effect of AaH-II on the AP generation in the AIS of neocortical layer-5 pyramidal neurons from mouse brain slices. After determining that AaH-II does not discriminate between Na1.2 and Na1.6, i.e. between the two VGNC isoforms expressed in this neuron, we established that 7 nM was the smallest toxin concentration producing a minimal detectable deformation of the somatic AP after local delivery of the toxin. Using membrane potential imaging, we found that, at this minimal concentration, AaH-II substantially widened the AP in the AIS. Using ultrafast Na imaging, we found that local application of 7 nM AaH-II caused a large increase in the slower component of the Na influx in the AIS. Finally, using ultrafast Ca imaging, we observed that 7 nM AaH-II produces a spurious slow Ca influx via Ca-permeable VGNCs. Molecules targeting VGNCs, including peptides, are proposed as potential therapeutic tools. Thus, the present analysis in the AIS can be considered a general proof-of-principle on how high-resolution imaging techniques can disclose drug effects that cannot be observed when tested at the macroscopic level.
Topics: Mice; Animals; Action Potentials; Axon Initial Segment; Scorpions; Peptides; Scorpion Venoms; Animals, Poisonous
PubMed: 38424206
DOI: 10.1038/s41598-024-55315-y -
Toxicon : Official Journal of the... Apr 2024Bee stings (BS) are a life-threatening issue and a growing concern for public health and animals in the Americas. We describe the clinical, pathological, and...
Bee stings (BS) are a life-threatening issue and a growing concern for public health and animals in the Americas. We describe the clinical, pathological, and ultrastructural findings of a massive lethal bee attack in two non-human primates (NHPs). Both animals showed BS scattered throughout the skin, surrounded by a local reaction, diffuse pulmonary congestion, edema, hemorrhage, and remarkable degeneration and necrosis of renal epithelial cells from the proximal and distal tubules, characterizing a systemic bee envenomation reaction.
Topics: Bees; Animals; Insect Bites and Stings; Saimiri; Bee Venoms; Primates; Cebinae
PubMed: 38423220
DOI: 10.1016/j.toxicon.2024.107666