The role and mechanism of NLRP3 in wasp venom-induced acute kidney injury.

BACKGROUND: Inflammation and pyroptosis have crucial impacts on the development of acute kidney injury (AKI) and have been validated in a variety of existing AKI animal models. However, the mechanisms underlying wasp venom-induced AKI are still unclear. The involvement of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) in some mouse models of AKI has been extensively documented, and its crucial function in controlling inflammation and pyroptosis has been highlighted. The objective of our study was to investigate the role and mechanism of NLRP3 in inflammation and pyroptosis associated with wasp venom-induced AKI. METHODS: A mouse model of AKI induced by wasp venom pre-injected with an NLRP3 inhibitor was used to study the role and mechanism of NLRP3. To verify the importance of NLRP3, western blotting was performed to assess the expression of NLRP3, caspase-1 p20, and gasdermin D (GSDMD)-N. Additionally, quantitative real-time polymerase was used to determine the expression of NLRP3, caspase-1, and GSDMD. Furthermore, enzyme-linked immunosorbent assay was utilized to measure the levels of interleukin (IL)-1ß and IL-18. RESULTS: NLRP3 was found to be the downstream signal of the stimulator of interferon genes in the wasp sting venom-induced AKI model. The administration of wasp venom in mice significantly upregulated the expression of NLRP3, leading to renal dysfunction, inflammation, and pyroptosis. Treatment with an NLRP3 inhibitor reversed the renal damage induced by wasp venom and attenuated pathological injury, inflammatory response, and pyroptosis. CONCLUSION: NLRP3 activation is associated with renal failure, inflammatory response and pyroptosis in the hyper early phase of wasp venom-induced AKI. The inhibition of NLRP3 significantly weakened this phenomenon. These findings could potentially offer a viable therapeutic approach for AKI triggered by wasp venom.

Wasp venom-induced acute kidney injury: current progress and prospects.

Wasp venom can trigger local and systemic reactions, with the kidneys being commonly affected, potentially causing acute kidney injury (AKI). Despite of the recent advances, our knowledge on the underlying mechanisms of toxicity and targeted therapies remain poor. AKI can result from direct nephrotoxic effects of the wasp venom or secondary rhabdomyolysis and intravascular hemolysis, which will release myoglobin and free hemoglobin. Inflammatory responses play a central role in these pathological mechanisms. Noteworthily, the successful establishment of a suitable experimental model can assist in basic research and clinical advancements related to wasp venom-induced AKI. The combination of therapeutic plasma exchange and continuous renal replacement therapy appears to be the preferred treatment for wasp venom-induced AKI. In addition, studies on cilastatin and varespladib for wasp venom-induced AKI treatment have shown their potential as therapeutic agents. This review summarizes the available evidence on the mechanisms and treatment of wasp venom-induced AKI, with a particular focus on the role of inflammatory responses and potential targets for therapeutic drugs, and, therefore, aiming to support the development of clinical treatment against wasp venom-induced AKI.

Megalin blockade with cilastatin ameliorates multiple wasp sting-induced acute kidney injury in rats.

Cilastatin has been shown to prevent various drug-induced nephrotoxicities and confer renoprotection in a mouse model of glycerol-mediated rhabdomyolysis-induced acute kidney injury (AKI). The present study aimed to investigate whether cilastatin attenuates wasp sting-induced AKI in rats. Male Wistar rats were divided into the control, cilastatin, AKI, and AKI + cilastatin groups. Nephrotoxicity was assessed using renal function, rhabdomyolysis (creatine kinase, CK) and intravascular hemolysis (lactate dehydrogenase, LDH) markers, and histological changes. In addition, tubular injury biomarkers, apoptosis, oxidative stress markers, complement C3 expression, and urine and blood myoglobin levels were examined. Compared with the control or cilastatin group, the AKI group showed significant histological damage, increased levels of CK, LDH, and creatinine, and increased mRNA expression of tubular injury biomarkers. Cilastatin ameliorated wasp venom-induced kidney injury by attenuating oxidative stress and apoptosis. Cilastatin also reduced C3 expression in the renal tubular cells. In addition, cilastatin reduced serum myoglobin levels and increased urine myoglobin concentrations. Therefore, megalin blockade with cilastatin attenuates wasp venom-induced AKI owing to its antioxidative and antiapoptotic properties.

Biological and Inflammatory Effects of Antigen 5 from Polybia paulista (Hymenoptera, Vespidae) Venom in Mouse Intraperitoneal Macrophages.

The social wasp Polybia paulista (Hymenoptera, Vespidae) is highly aggressive, being responsible for many medical occurrences. One of the most allergenic components of this venom is Antigen 5 (Poly p 5). The possible modulation of the in vitro immune response induced by antigen 5 from P. paulista venom, expressed recombinantly (rPoly p 5), on BALB/c mice peritoneal macrophages, activated or not with LPS, was assessed. Here, we analyzed cell viability changes, expression of the phosphorylated form of p65 NF-κB subunit, nitric oxide (NO), proinflammatory cytokines production, and co-stimulatory molecules (CD80, CD86). The results suggest that rPoly p 5 does not affect NO production nor the expression of co-stimulatory molecules in mouse peritoneal macrophages. On the other hand, rPoly p 5 induced an increase in IL-1ß production in non-activated macrophages and a reduction in the production of TNF-α and MCP-1 cytokines in activated macrophages. rPoly p 5 decreased the in vitro production of the phosphorylated p65 NF-κB subunit in non-activated macrophages. These findings suggest an essential role of this allergen in the polarization of functional M2 macrophage phenotypes, when analyzed in previously activated macrophages. Further investigations, mainly in in vivo studies, should be conducted to elucidate Polybia paulista Ag5 biological role in the macrophage functional profile modulation.

Comprehensive Analysis and Biological Characterization of Venom Components from Solitary Scoliid Wasp Campsomeriella annulata annulata.

Venoms of solitary wasps are utilized for prey capture (insects and spiders), paralyzing them with a stinger injection to be offered as food for their larvae. Thus, the identification and characterization of the components of solitary wasp venoms can have biotechnological application. In the present study, the venom components profile of a solitary scoliid wasp, Campsomeriella annulata annulata, was investigated through a comprehensive analysis using LC-MS and -MS/MS. Online mass fingerprinting revealed that the venom extract contains 138 components, and MS/MS analysis identified 44 complete sequences of the peptide components. The peptides are broadly divided into two classes: bradykinin-related peptides, and linear α-helical peptides. Among the components of the first class, the two main peptides, α-campsomerin (PRLRRLTGLSPLR) and ß-campsomerin (PRLRRLTGLSPLRAP), had their biological activities evaluated. Both peptides had no effects on metallopeptidases [human neprilysin (NEP) and angiotensin-converting enzyme (ACE)] and acetylcholinesterase (AChE), and had no cytotoxic effects. Studies with PC12 neuronal cells showed that only α-campsomerin was able to enhance cell viability, while ß-campsomerin had no effect. It is noteworthy that the only difference between the primary structures from these peptides is the presence of the AP extension at the C-terminus of ß-campsomerin, compared to α-campsomerin. Among the linear α-helical peptides, annulatin (ISEALKSIIVG-NH2) was evaluated for its biological activities. Annulatin showed histamine releasing activity from mast cells and low hemolytic activity, but no antimicrobial activities against all microbes tested were observed. Thus, in addition to providing unprecedented information on the whole components, the three peptides selected for the study suggest that molecules present in solitary scoliid wasp venoms may have interesting biological activities.

An integrated transcriptomic and proteomic approach to identify the main Torymus sinensis venom components.

During oviposition, ectoparasitoid wasps not only inject their eggs but also a complex mixture of proteins and peptides (venom) in order to regulate the host physiology to benefit their progeny. Although several endoparasitoid venom proteins have been identified, little is known about the components of ectoparasitoid venom. To characterize the protein composition of Torymus sinensis Kamijo (Hymenoptera: Torymidae) venom, we used an integrated transcriptomic and proteomic approach and identified 143 venom proteins. Moreover, focusing on venom gland transcriptome, we selected additional 52 transcripts encoding putative venom proteins. As in other parasitoid venoms, hydrolases, including proteases, phosphatases, esterases, and nucleases, constitute the most abundant families in T. sinensis venom, followed by protease inhibitors. These proteins are potentially involved in the complex parasitic syndrome, with different effects on the immune system, physiological processes and development of the host, and contribute to provide nutrients to the parasitoid progeny. Although additional in vivo studies are needed, initial findings offer important information about venom factors and their putative host effects, which are essential to ensure the success of parasitism.

Macroscopic hematuria in wasp sting patients: a retrospective study.

BACKGROUND: Macroscopic hematuria after wasp sting has been reported in Asia to occur before acute kidney injury (AKI), and is often used by clinicians as a sign indicating the need for intensive care and blood purification therapy. However, there is no study on the clinical characteristics and prognosis of this symptom. METHODS: The clinical data of 363 patients with wasp sting admitted to Suining Central Hospital from January 2016 to December 2018 were retrospectively analyzed. At admission, the poisoning severity score (PSS) was used as the criterion for severity classification. According to the presence of macroscopic hematuria, the patients were divided into macroscopic hematuria and non-macroscopic hematuria group. RESULTS: Of the 363 wasp sting patients, 219 were male and 144 were female, with a mean age of 55.9 ± 16.3 years. Fifty-one (14%) had macroscopic hematuria, 39 (10.7%) had AKI, 105 (28.9%) had rhabdomyolysis, 61 (16.8%) had hemolysis, 45 (12.4%) went on to received hemodialysis, and 14 (3.9%) died. The incidence of AKI in macroscopic hematuria group was 70.6%, and oliguric renal failure accounted for 72.2%. Patients with macroscopic hematuria had significantly higher PSS (2.2 ± 0.5 vs. 1.1 ± 0.3, p < .001). CONCLUSION: Macroscopic hematuria can be regarded as a surrogate marker of deteriorating clinical outcome following wasp stings. In wasp sting patients with symptoms of macroscopic hematuria or serum LDH higher than 463.5 u/L upon admission, the risk of AKI increases significantly, therefore hemodialysis should be considered. The PSS is helpful in early assessment of the severity of wasp sting patients.

Sweet as honey, bitter as bile: Mitochondriotoxic peptides and other therapeutic proteins isolated from animal tissues, for dealing with mitochondrial apoptosis.

Mitochondria are subcellular organelles involved in cell metabolism and cell life-cycle. Their role in apoptosis regulation makes them an interesting target of new drugs for dealing with cancer or rare diseases. Several peptides and proteins isolated from animal and plant sources are known for their therapeutic properties and have been tested on cancer cell-lines and xenograft murine models, highlighting their ability in inducing cell-death by triggering mitochondrial apoptosis. Some of those molecules have been even approved as drugs. Conversely, many other bioactive compounds are still under investigation for their proapoptotic properties. In this review we report about a group of peptides, isolated from animal venoms, with potential therapeutic properties related to their ability in triggering mitochondrial apoptosis. This class of compounds is known with different names, such as mitochondriotoxins or mitocans.

Pro-inflammatory response induced by the venom of Parachartergus fraternus wasp.

The sting of different wasp species triggers local and systemic reactions in victims that can lead to death. Parachartergus fraternus is responsible for frequent accidents in Latin America; however, few studies have been conducted on this insect and its venom. In this study, the inflammatory process induced by the venom of the P. fraternus wasp (Pfv; 100, 200, and 400 µg/kg) was characterized. Mice were used to assess paw edema, vascular permeability, mast cell degranulation, leukocyte influx, nitric oxide (NO) production, expression of inflammatory genes, and histopathological changes. Pfv triggered edema formation with a peak dose of 200 µg/kg at 10 min. There was an increase in permeability in all periods and doses evaluated, with no differences between them. The 200 µg/kg dose induced mast cell degranulation in all periods, with a peak at 15 min. This same dose induced leukocyte influx with a predominance of mononuclear cells and triggered a peak in NO production in the 12th hour. The increase in COX-2, iNOS, and IFN-γ mRNA expression occurred after 1 and 6 h, and there was an increase in IL-10 expression after 48 h. In addition, Pfv triggered edema and induced an influx of macrophages and mast cells into the injection site. Therefore, Pfv induces an inflammatory process from the first 5 min of inoculation that can persist for up to 48 h.

Repurposing a peptide toxin from wasp venom into antiinfectives with dual antimicrobial and immunomodulatory properties.

Novel antibiotics are urgently needed to combat multidrug-resistant pathogens. Venoms represent previously untapped sources of novel drugs. Here we repurposed mastoparan-L, the toxic active principle derived from the venom of the wasp Vespula lewisii, into synthetic antimicrobials. We engineered within its N terminus a motif conserved among natural peptides with potent immunomodulatory and antimicrobial activities. The resulting peptide, mast-MO, adopted an α-helical structure as determined by NMR, exhibited increased antibacterial properties comparable to standard-of-care antibiotics both in vitro and in vivo, and potentiated the activity of different classes of antibiotics. Mechanism-of-action studies revealed that mast-MO targets bacteria by rapidly permeabilizing their outer membrane. In animal models, the peptide displayed direct antimicrobial activity, led to enhanced ability to attract leukocytes to the infection site, and was able to control inflammation. Permutation studies depleted the remaining toxicity of mast-MO toward human cells, yielding derivatives with antiinfective activity in animals. We demonstrate a rational design strategy for repurposing venoms into promising antimicrobials.

Risk factors of acute kidney injury induced by multiple wasp stings.

In Asia, acute kidney injury (AKI) induced by wasp stings is common; however, the pathophysiological mechanisms involved remain unclear. To evaluate the mechanisms associated with AKI induced by wasp stings, we conducted a retrospective cohort study that assessed blood and urinary samples from 112 patients with hospital admissions resulting from wasp stings. These samples were divided into those with AKI and without AKI as described in the Kidney Disease Improving Global Outcomes (KDIGO) database. Of the patients, 48.2% presented with an elevated number of leukocytes (median 19.9 vs. 15.8 × 109/L), serum creatinine (median 122.0 vs. 66.0 µmol/L), alanine aminotransferase (ALT) (median 176 vs. 32 U/L), aspartate aminotransferase (AST) (median 402 vs. 37 U/L), lactate dehydrogenase (LDH) (median 3076.0 vs. 300.0 U/L), creatine kinase (CK) (median 9990.0 vs. 261.0 U/L), creatine kinase myocardial band (CK-mb) (median 200.0 vs. 29.5 U/L), activated partial thromboplastin time (APTT) (median 70.0 vs. 42.5s), prothrombin time (PT) (median 15.0 vs. 12.5s), myoglobin (median 2200.0 vs. 78.0 ng/mL), proteinuria (51.9% vs. 17.2% ≥ 1+), and urinary monocyte chemotactic protein-1 (MCP-1) (median 432.0 vs. 177.0 pg/mL), and subsequently developed AKI. As determined by multivariate logistic regression analysis, elevated leukocytes (>10 × 109/L) [OR 1.12 (95% CI 1.02-1.23)], high myoglobin (>1200 ng/mL) [OR 18.51 (95% CI 1.51-132.27)], and high urinary MCP-1 (>200 pg/mL) [OR 5.42 (95% CI 1.27-30.39)] on admission were independent risk factors for AKI. At admission, baseline values for ALT, aspartate aminotransferase (AST), LDH, CK-mb, APTT, PT, and proteinuria were higher for those who later died as well as for those who developed end-stage renal disease (ESRD). No patients without AKI died or developed ESRD. The present study explored the pathophysiology of AKI induced by wasp stings based on the findings of risk factors as well as factors related to outcomes. An understanding of AKI induced by wasp stings allows better treatment options and clinical management for wasp stings patients.

Wasp venom peptide as a new antichagasic agent.

Chagas disease is caused by Trypanosoma cruzi and affects approximately 10 million people a year worldwide. The only two treatment options, benznidazole and nifurtimox, have low efficacy and high toxicity towards human cells. Mastoporan peptide (MP) a small cationic AMP from the venom of the wasp Polybia paulista has been reported as a potent trypanocidal agent. Thus, we evaluated the antichagasic effect of another AMP from the venom of the same wasp Polybia paulista, polybia-CP (ILGTILGLLSKL-NH2), and investigated its mechanism of action against different stages of the trypanosomal cells life cycle. Polybia-CP was tested against the epimastigote, trypomastigote and amastigote forms of the T. cruzi Y strain (benznidazole-resistant strain) and inhibited the development of these forms. We also assessed the selectivity of the AMP against mammalian cells by exposing LLC-MK2 cells to polybia-CP, the peptide presented a high selectivity index (>106). The mechanism of action of polybia-CP on trypanosomal cells was investigated by flow cytometry, scanning electron microscopy (SEM) and enzymatic assays with T. cruzi GAPDH (tcGAPDH), enzyme that catalyzes the sixth step of glycolysis. Polybia-CP induced phosphatidylserine exposure, it also increased the formation of reactive species of oxigen (ROS) and reduced the transmembrane mitochondrial potential. Polybia-CP also led to cell shrinkage, evidencing apoptotic cell death. We did not observe the inhibition of tcGAPDH or autophagy induction. Altogether, polybia-CP has shown the features of a promising template for the development of new antichagasic agents.

[Antagonistic effect of the Fengzhecao extract against human red blood cell hemolysis induced by wasp venom].

OBJECTIVE: To explore the antagonistic effect of Fengzhecao extract against human red blood cell (RBC) hemolysis induced by wasp venom. METHODS: Water extract method was used to extract dried Fengzhecao and vacuum-dried to obtain Fengzhecao extract. It was diluted into 1 g/L for next use. Wasp venom was collected from the wasp workers. A, B, O, AB type healthy blood donors' suspended RBC solution was obtain to make washed RBC solutions and adjust the RBCs count (4.0-80.0)×109/L (the number of RBC counted on the hemocytometer is 1-20 cells/small checker). According to treatment factors, they were divided into the normal saline controlled group (NS group; 200 µL RBC solution+20 µL normal saline), Fengzhecao extract group (FZC group; 200 µL RBC solution+10 µL Fengzhecao extract+10 µL normal saline), wasp venom group (FD group; 200 µL RBC solution+10 µL wasp venom+10 µL normal saline), and Fengzhecao extract+wasp venom group (FCD group; 200 µL RBC solution+10 µL Fengzhecao extract+10 µL wasp venom), with 10 blood samples per group of every blood type. The solutions were put into the glass test tube respectively, and then into 37 centigrade water bath thermostat. After 10 minutes, the blood cell counting plate was directly observed under the microscope and the RBCs was counted. Differences in RBC count was compared between the same treatment factors of different blood types and between different treatment factor groups of the same blood type. RESULTS: There was no statistically significant difference in RBC count between blood types under the same treatment factors. The RBC count (×109/L) of the type A, B, O, AB in the NS group were 5.567±1.368, 5.146±1.690, 4.577±0.774, 5.197±1.587 (F = 0.852, P = 0.475), the FZC group were 5.751±1.489, 5.268±1.418, 4.727±1.174, 5.298±1.229 (F = 0.987, P = 0.410), the FD group were 0.546±0.450, 0.804±0.428, 0.679±0.283, 0.846±0.453 (F = 1.089, P = 0.366), and the FCD group were 5.532±1.330, 5.051±1.596, 4.589±0.879, 5.140±1.492 (F = 0.820, P = 0.492), respectively. Comparison of RBC count between groups with different treatment factors of the same blood type was done. There was no significant difference between the FZC group and the NS group, indicating that the extract of Fengzhecao extract had no effect on hemolysis of RBC; in the FD group, it was significantly lower than the NS group (all P < 0.05), indicating that wasp venom had a significant hemolytic effect on RBC; but there was no statistically significant difference in RBC count between the FCD group and the NS group, indicating that the Fengzhecao extract antagonizes the hemolytic effect of wasp venom without affecting the RBC count; however, the RBC count in the FCD group was significantly higher than that in the FD group (all P < 0.05), further indicating that the Fengzhecao extract antagonizes the hemolytic effect of wasp venom. CONCLUSIONS: Wasp venom has a significant hemolytic effect which can be effectively antagonized by Fengzhecao extract and has nothing to do with the human ABO blood type.

Identifying the toxins in hornet (Vespa basalis) venom that induce rat pain responses.

The black-bellied hornet Vespa basalis is responsible for the large quantity of accidents and severe wasp envenomation in China. This study aims to identify the rat pain responses induced by experimental V. basalis sting and related-components in the venom. It was observed that unilateral intraplantar injection of crude V. basalis venom could induce several kinds of pain related behaviors in a dose-dependent manner including spontaneous pain, unilateral thermal and unilateral mechanical hypersensitivity at different time courses. Fourteen main fractions were separated from the crude venom of V. basalis using high performance liquid chromatography, among them, five components (1, 3, 4, 9 and 12) could absolutely mimic the crude venom-induced pain behaviors. According to the molecular mass and N-terminal sequence, the component 3 and 4 were identified as Mastoparan B and HP-1 respectively, the component 9 was speculated as a novel variant of HP-1/2. In addition, the other two sub-components (1-1 and 1-2) purified from component 1 cannot be determined. The results offered the key information about six active polypeptides from V. basalis contributing to pain responses, which might provide a basis for exploring mechanisms of wasp sting injury.

What's eating you? vespids revisited.

The Hymenoptera order of insects includes Apidae (bees), Vespidae (wasps, yellow jackets, hornets), and Formicidae (fire ants). All 3 of these families of insects inject venom into their prey or as a defense mechanism via ovipositors in their abdomen. Three types of reactions can be seen after a vespid sting: uncomplicated local reactions, large local reactions, and systemic reactions (SRs). Although many vespid stings can be managed symptomatically, it is imperative for patients and providers to be aware of the possible severe reactions that can take place.

Responses of sericotropin to toxic and pathogenic challenges: possible role in defense of the wax moth Galleria mellonella.

This study describes defense functions of the insect neuropeptide sericotropin, which is recognized as an agent that stimulates silk production in some lepidopteran larvae. Sericotropin, expressed in brain tissue of the wax moth Galleria mellonella in all developmental stages, is not expressed in silk glands, indicating its tissue specificity. Fluorescence microscopy confirmed the presence of sericotropin in the brain-subesophageal complex being predominantly and densely distributed under the plasmatic membrane and in axonal parts of neurons. Injection of venom from Habrobracon hebetor and topical application of the entomopathogenic nematode (EPN) Steinernema carpocapsae with symbiotic bacteria Xenorhabdus spp. into or onto G. mellonella larvae resulted in upregulation of the sericotropin gene and peptide, suggesting a role for sericotropin in defense and immunity. Accordingly, two synthetic fragments of sericotropin killed entomotoxic Xenorhabdus spp. bacteria in a disc diffusion antimicrobial test. Further, total metabolism, monitored by carbon dioxide production, significantly decreased after application of either venom or EPN, probably because of muscle impairment by the venom and serious cell damage caused by EPN, especially in the midgut. Both venom and EPN upregulated expression of genes encoding antimicrobial peptides gallerimycin and galiomicin in Galleria brain; however, they downregulated prophenoloxidase and phenoloxidase activity in hemolymph. These results suggest that sericotropin is a multifunctional peptide that plays an important role in G. mellonella defense and immunity.

Study of mastoparan analog peptides against Candida albicans and safety in zebrafish embryos (Danio rerio).

Aim: In this work, mastoparan analog peptides from wasp venom were tested against Candida albicans and safety assays were performed using cell culture and model zebrafish. Materials & methods: Minimal inhibitory concentration was determined and toxicity was performed using human skin keratinocyte and embryo zebrafish. Also, permeation of peptides through embryo chorion was performed. Results: The peptides demonstrated anti-C. albicans activity, with low cytotoxicity and nonteratogenicity in Danio rerio. The compounds had different permeation through chorion, suggesting that this occurs due to modifications in their amino acid sequence. Conclusion: The results showed that the studied peptides can be used as structural study models for novel potential antifungal agents.

Effect of natural toxins and adipokinetic hormones on the activity of digestive enzymes in the midgut of the cockroach Periplaneta americana.

This study examined the effect of two natural toxins (a venom from the parasitic wasp Habrobracon hebetor and destruxin A from the entomopathogenic fungus Metarhizium anisopliae), and one pathogen (the entomopathogenic fungus Isaria fumosorosea) on the activity of basic digestive enzymes in the midgut of the cockroach Periplaneta americana. Simultaneously, the role of adipokinetic hormones (AKH) in the digestive processes was evaluated. The results showed that all tested toxins/pathogens elicited stress responses when applied into the cockroach body, as documented by an increase of AKH level in the central nervous system. The venom from H. hebetor showed no effect on digestive enzyme activities in the ceca and midgut in vitro. In addition, infection by I. fumosorosea caused a decrease in activity of all enzymes in the midgut and a variable decrease in activity in the ceca; application of AKHs did not reverse the inhibition. Destruxin A inhibited the activity of all enzymes in the midgut but none in the ceca in vitro; application of AKHs did reverse this inhibition, and no differences between both cockroach AKHs were found. Overall, the results demonstrated the variable effect of the tested toxins/pathogens on the digestive processes of cockroaches as well as the variable ability of AKH to counteract these effects.

Clinical consequences of toxic envenomations by Hymenoptera.

Many familiar Hymenoptera are brightly colored and can sting painfully-thus, their threat and clinical importance may be exaggerated. Most stinging insects only sting to defend themselves or their colonies from predators. The clinical nature of Hymenoptera envenomations contrasts that of other venomous animals, including other arthropods, primarily because allergic reaction, not direct intoxication, is the usual main concern. This review focuses mainly on the clinical features of direct toxicity to Hymenoptera envenomations, which can induce a high incidence of acute renal failure, liver failure, multiple organ failures, and death. Toxic mass envenomations by honeybees usually entail many hundreds or more stings per victim. In contrast to honeybee toxic envenomations, hornet sting envenomations can be clinically threatening with only 20-200 stings needed to cause kidney and other organ failures. Many lethal envenomations by honeybees occur in rural areas in the New World and Africa and are not recorded or documented. In contrast, deaths by hornets occur mainly to Asia. The most frequent and important envenomating taxa are honeybees, hornets, yellowjacket wasps, paper wasps, fire ants, and jack jumper ants. Occasional envenomating taxa include bumblebees, bullet ants, harvester ants, solitary wasps, solitary bees, and various ants of lesser clinical importance. Envenomations by Hymenoptera usually can be avoided if one considers that bees, wasps and ants "view" us as potential threats or predators, and that with information about the biology of stinging Hymenoptera, humans can minimize adverse incidents.

A membrane disrupting toxin from wasp venom underlies the molecular mechanism of tissue damage.

The molecular mechanism of the local hypersensitivity reactions to wasp venom including dermal necrosis remains an enigma regardless of the numerosity of the reported cases. In this study, we discovered a new membrane disrupting toxin, VESCP-M2 responsible for tissue damage symptoms following Vespa mandarinia envenomation. Electrophysiological assays revealed a potent ability of VESCP-M2 to permeate the cell membrane whereas in vivo experiments demonstrated that VESCP-M2 induces edema, pain and dermal necrosis characterized by the presence of morphological and behavioral phenotypes, pro-inflammatory mediators, biomarkers as well as the disruption of dermal tissue. This study presents the molecular mechanism and symptom-related function of VESCP-M2 which may form a basis for prognosis as well as therapeutic interventions.