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Renal Failure Dec 2024Previous studies have highlighted the significant role of complement activation in kidney injuries induced by rhabdomyolysis, intravascular hemolysis, sepsis, and...
Previous studies have highlighted the significant role of complement activation in kidney injuries induced by rhabdomyolysis, intravascular hemolysis, sepsis, and ischemia-reperfusion. Nevertheless, the specific role and mechanism of complement activation in acute kidney injury (AKI) caused by wasp venom remain unclear. The aim of this study was to elucidate the specific complement pathway activated and investigate complement activation in AKI induced by wasp venom. In this study, a complement-depleted mouse model was used to investigate the role of complement in wasp venom-induced AKI. Mice were randomly categorized into control, cobra venom factor (CVF), AKI, and CVF + AKI groups. Compared to the AKI group, the CVF + AKI group showed improved pathological changes in kidneys and reduced blood urea nitrogen (BUN) levels. The expression levels of renal complement 3 (C3), complement 5 (C5), complement 1q (C1q), factor B (FB), mannose-binding lectin (MBL), and C5b-9 in AKI group were upregulated compared with the control group. Conversely, the renal tissue expression levels of C3, C5, C1q, FB, MBL, and C5b-9 were decreased in the CVF + AKI group compared to those in the AKI group. Complement activation occurs through all three pathways in AKI induced by wasp venom. Furthermore, complement depletion by CVF attenuates wasp venom-induced nephrotoxicity, suggesting that complement activation plays a primary role in the pathogenesis of wasp venom-induced AKI.
Topics: Animals; Acute Kidney Injury; Complement Activation; Mice; Disease Models, Animal; Wasp Venoms; Male; Kidney; Elapid Venoms; Blood Urea Nitrogen; Complement C3; Complement System Proteins
PubMed: 38644359
DOI: 10.1080/0886022X.2024.2344658 -
Biomedicine & Pharmacotherapy =... May 2024Neuronal ferroptosis and autophagy are crucial in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Mastoparan M (Mast-M), extracted from the crude venom...
Neuronal ferroptosis and autophagy are crucial in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Mastoparan M (Mast-M), extracted from the crude venom of Vespa magnifica (Smith), comprises 14 amino acid residues. Previous studies suggested that Mast-M reduces neuronal damage following global CIRI, but its protective mechanisms remain unclear. The present study examined the effect of Mast-M on middle cerebral artery occlusion/reperfusion (MCAO/R) induced neurological deficits using Grip, Rotarod, Longa test, and TTC staining, followed by treating the mice for three days with Mast-M (20, 40, and 80 μg/kg, subcutaneously). The results demonstrate that Mast-M promotes functional recovery in mice post-ischemic stroke, evidenced by improved neurological impairment, reduced infarct volume and neuronal damage. Meanwhile, the level of iron (Fe) and malonyldialdehyde was decreased in the ischemic hemisphere of MCAO/R mice at 24 hours or 48 hours by Mast-M (80 μg/kg) treatment, while the expression of NRF2, x-CT, GPX4, and LC3B protein was increased. Furthermore, these findings were validated in three models-oxygen-glucose deprivation/ reoxygenation, HO-induced peroxidation, and erastin-induced ferroptosis-in hippocampal neuron HT22 cells or primary neurons. These data suggested that Mast-M activates autophagy as well as inhibits ferroptosis. Finally, autophagy inhibitors were introduced to determine the relationship between the autophagy and ferroptosis, indicating that Mast-M alleviates ferroptosis by activating autophagy. Taken together, this study described that Mast-M alleviates cerebral infarction, neurologic impairment, and neuronal damage by activating autophagy and inhibiting ferroptosis, presenting a potential therapeutic approach for CIRI.
Topics: Animals; Autophagy; Ferroptosis; Male; Mice; Recovery of Function; Infarction, Middle Cerebral Artery; Mice, Inbred C57BL; Wasp Venoms; Neuroprotective Agents; Reperfusion Injury; Neurons; Disease Models, Animal; Stroke
PubMed: 38583338
DOI: 10.1016/j.biopha.2024.116560 -
Nuclear Medicine and Biology 2024DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors...
Investigation of imaging the somatostatin receptor by opening the blood-brain barrier with melittin - A feasibility study using positron emission tomography and [Cu]Cu-DOTATATE.
DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors are found naturally in the intestines, pancreas, lungs, and brain (mainly cortex). In vivo measurement of the somatostatin receptors in the cortex has been challenging because available tracers cannot cross the blood-brain barrier (BBB) due to their intrinsic polarity. A peptide called melittin, a main component of honeybee venom, has been shown to disrupt plasma membranes and increase the permeability of biological membranes. In this study, we assessed the feasibility of using melittin to facilitate the passage of [Cu]Cu-DOTATATE through the BBB and its binding to somatostatin receptors in the cortex. Evaluation included in vitro autoradiography on Long Evans rat brains to estimate the binding affinity of [Cu]Cu-DOTATATE to the somatostatin receptors in the cortex and an in vivo evaluation of [Cu]Cu-DOTATATE binding in NMRI mice after injection of melittin. This study found an in vitro B = 89 ± 4 nM and K = 4.5 ± 0.6 nM in the cortex, resulting in a theoretical binding potential (BP) calculated as B/K ≈ 20, which is believed suitable for in vivo brain PET imaging. However, the in vivo results showed no significant difference between the control and melittin injected mice, indicating that the honeybee venom failed to open the BBB. Additional experiments, potentially involving faster injection rates are required to verify that melittin can increase brain uptake of non-BBB permeable PET tracers. Furthermore, an evaluation of whether a venom with a narrow therapeutic range can be used for clinical purposes needs to be considered.
Topics: Animals; Receptors, Somatostatin; Melitten; Rats; Feasibility Studies; Positron-Emission Tomography; Organometallic Compounds; Blood-Brain Barrier; Male; Mice; Copper Radioisotopes; Octreotide
PubMed: 38555651
DOI: 10.1016/j.nucmedbio.2024.108905 -
International Journal of Molecular... Mar 2024Allergen-specific venom immunotherapy (VIT) is a well-established therapy for venom allergy (HVA). However, the precise mechanism underlying its clinical effect remains...
Allergen-specific venom immunotherapy (VIT) is a well-established therapy for venom allergy (HVA). However, the precise mechanism underlying its clinical effect remains uncertain. Our study aimed to identify the molecular mechanisms associated with VIT efficiency. We prospectively included 19 patients with HVA undergoing VIT (sampled before the beginning of VIT, after reaching the maintenance dose, one year after finishing VIT, and after a sting challenge) and 9 healthy controls. RNA sequencing of whole blood was performed on an Illumina sequencing platform. Longitudinal transcriptomic profiling revealed the importance of the inhibition of the NFκB pathway and the downregulation of transcripts for the early protection and induction of tolerance after finishing VIT. Furthermore, successful treatment was associated with inhibiting Th2, Th17, and macrophage alternative signalling pathways in synergy with the inhibition of the PPAR pathway and further silencing of the Th2 response. The immune system became activated when reaching the maintenance dose and was suppressed after finishing VIT. Finally, successful VIT restores the immune system's balance to a state similar to that of healthy individuals. Our results underline the important role of the inhibition of four pathways in the clinical effect of VIT: Th2, Th17, NFκB, and macrophage signalling. Two biomarkers specific for successful VIT, regardless of the time of sampling, were and and should be further tested as potential biomarkers.
Topics: Animals; Humans; Arthropod Venoms; Hymenoptera; Desensitization, Immunologic; Hypersensitivity; Treatment Outcome; Immunotherapy; Biomarkers; Gene Expression Profiling; Gene Expression
PubMed: 38542470
DOI: 10.3390/ijms25063499 -
Toxins Mar 2024More recently, short peptides in scorpion venom have received much attention because of their potential for drug discovery. Although various biological effects of these...
More recently, short peptides in scorpion venom have received much attention because of their potential for drug discovery. Although various biological effects of these short peptides have been found, their studies have been hindered by the lack of structural information especially in modifications. In this study, small peptides from scorpion venom were investigated using high-performance liquid chromatography high-resolution mass spectrometry followed by de novo sequencing. A total of 156 sequences consisting of 2~12 amino acids were temporarily identified from scorpion venom. The identified peptides exhibited various post-translational modifications including N-terminal and C-terminal modifications, in which the N-benzoyl modification was first found in scorpion venom. Moreover, a short peptide Bz-ARF-NH demonstrated both N-terminal and C-terminal modifications simultaneously, which is extremely rare in natural peptides. In conclusion, this study provides a comprehensive insight into the diversity, modifications, and potential bioactivities of short peptides in scorpion venom.
Topics: Amino Acids; Liquid Chromatography-Mass Spectrometry; Peptides; Scorpion Venoms; Animals, Poisonous; Scorpions
PubMed: 38535821
DOI: 10.3390/toxins16030155 -
Toxins Mar 2024Viruses are one of the leading causes of human disease, and many highly pathogenic viruses still have no specific treatment drugs. Therefore, producing new antiviral...
Viruses are one of the leading causes of human disease, and many highly pathogenic viruses still have no specific treatment drugs. Therefore, producing new antiviral drugs is an urgent matter. In our study, we first found that the natural wasp venom peptide Protopolybia-MP III had a significant inhibitory effect on herpes simplex virus type 1 (HSV-1) replication by using quantitative real-time PCR (qPCR), Western blotting, and plaque-forming assays. Immunofluorescence analysis showed Protopolybia-MP III could enter cells, and it inhibited multiple stages of the HSV-1 life cycle, including the attachment, entry/fusion, and post-entry stages. Furthermore, ultracentrifugation and electron microscopy detected that Protopolybia-MP III significantly suppressed HSV-1 virion infectivity at different temperatures by destroying the integrity of the HSV-1 virion. Finally, by comparing the antiviral activity of Protopolybia-MP III and its mutants, a series of peptides with better anti-HSV-1 activity were identified. Overall, this work found the function and mechanism of the antiviral wasp venom peptide Protopolybia-MP III and its derivatives against HSV-1 and laid the foundation for the research and development of wasp venom-derived antiviral candidate peptide drugs.
Topics: Humans; Animals; Herpesvirus 1, Human; Wasp Venoms; Biological Assay; Peptides; Wasps; Antiviral Agents
PubMed: 38535798
DOI: 10.3390/toxins16030132 -
Toxins Feb 2024Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and... (Review)
Review
Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and venom has been studied the most extensively. Numerous studies dealing with the positive assets of bee venom (BV) indicated its beneficial properties. The usage of bee products to prevent the occurrence of diseases and for their treatment is often referred to as apitherapy and is based mainly on the experience of the traditional system of medical practice in diverse ethnic communities. Today, a large number of studies are focused on the antitumor effects of BV, which are mainly attributed to its basic polypeptide melittin (MEL). Previous studies have indicated that BV and its major constituent MEL cause a strong toxic effect on different cancer cells, such as liver, lung, bladder, kidney, prostate, breast, and leukemia cells, while a less pronounced effect was observed in normal non-target cells. Their proposed mechanisms of action, such as the effect on proliferation and growth inhibition, cell cycle alterations, and induction of cell death through several cancer cell death mechanisms, are associated with the activation of phospholipase A (PLA), caspases, and matrix metalloproteinases that destroy cancer cells. Numerous cellular effects of BV and MEL need to be elucidated on the molecular level, while the key issue has to do with the trigger of the apoptotic cascade. Apoptosis could be either a consequence of the plasmatic membrane fenestration or the result of the direct interaction of the BV components with pro-apoptotic and anti-apoptotic factors. The interaction of BV peptides and enzymes with the plasma membrane is a crucial step in the whole process. However, before its possible application as a remedy, it is crucial to identify the correct route of exposure and dosage of BV and MEL for potential therapeutic use as well as potential side effects on normal cells and tissues to avoid any possible adverse event.
Topics: Male; Animals; Bees; Bee Venoms; Melitten; Cell Membrane; Apoptosis; Cell Death
PubMed: 38535786
DOI: 10.3390/toxins16030117 -
Toxicon : Official Journal of the... May 2024A key aspect during the development of antivenoms is the evaluation of the efficiency and security of the therapeutic molecules. In this work, we report the...
A key aspect during the development of antivenoms is the evaluation of the efficiency and security of the therapeutic molecules. In this work, we report the pharmacokinetic analysis of a neutralizing single chain antibody fragment named LR (scFv LR) where three sheep were used as a large animal model. The animals were injected through i.v. route with 2 mg of scFv LR. Blood samples were drawn every minute within the first 15 min, the sampling continues at 20, 25, 30, 45, 60, 90, 120 min, subsequently at 1-h intervals, 3, 4, 5, 6 h, two more samples at 9 and 12 h and, two more samples at 24 and 48 h and finally at one-day intervals during 4 days. scFv LR levels were measured from blood serum and urine samples by an ELISA. The pharmacokinetics of the experimental data was analyzed using the three-exponential kinetics. The value of the fast initial component (τ=0.409±0.258min) indicated that the scFv is distributed rapidly into the tissues. The mean residence time, MRT, was 45 ± 0.51 min and the clearance (CL), 114.3 ± 14.3 mL/min. From urine samples it was possible to detect significant amounts of scFv LR, which is evidence of renal elimination.
Topics: Animals; Single-Chain Antibodies; Sheep; Scorpion Venoms; Antivenins; Scorpions
PubMed: 38522587
DOI: 10.1016/j.toxicon.2024.107691 -
Iranian Journal of Allergy, Asthma, and... Feb 2024Little is known about the quality of life of patients with anaphylaxis to Hymenoptera venom. The Vespid Allergy Quality of Life Questionnaire (VQLQ) is commonly used to...
Little is known about the quality of life of patients with anaphylaxis to Hymenoptera venom. The Vespid Allergy Quality of Life Questionnaire (VQLQ) is commonly used to assess the psychological burden of this condition. This study aimed to evaluate the validity and reliability of the Persian version of VQLQ. In this cross-sectional study, VQLQ was translated into Persian according to expert recommendations. The final translated version of VQLQ was then administered to 115 patients with Hymenoptera venom allergy at an asthma and allergy clinic in Iran. More than half of the participants were between 20 and 40 years of age, and 60% were male. Fear, anxiety, and outdoor activities had the most significant impact on the quality of life of patients with Hymenoptera venom allergy. Additionally, quality of life was more affected in women than in men, while no correlation was found with age. Furthermore, the quality of life was affected by a history of acute anaphylactic shock due to Hymenoptera venom. The Persian version of VQLQ enables the measurement of quality of life in patients with Hymenoptera venom allergy in the Iranian population. The inclusion of VQLQ in the initial evaluation of these patients may potentially guide allergist in providing support for venom-specific immunotherapy.
Topics: Animals; Humans; Male; Female; Anaphylaxis; Arthropod Venoms; Iran; Quality of Life; Cross-Sectional Studies; Reproducibility of Results; Insect Bites and Stings; Desensitization, Immunologic; Hymenoptera
PubMed: 38485910
DOI: 10.18502/ijaai.v23i1.14954 -
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