Introduction: Toxoplasmosis is an alarming public health problem that affects more than one-third of the global population. We investigated the antiparasitic effects of MjTX-II, a Lys-49-PLA₂ from Bothrops moojeni, in human trophoblast cells and villous explants. Methods: MjTX-II was purified using two ion-exchange chromatographic steps and characterized through biochemical and proteomic analyses. The BeWo cells' viability was assessed using an MTT assay. The impact of MjTX-II on T. gondii was evaluated via trypan blue staining and scanning electron microscopy. The effect on the parasite's adhesion and invasion was assessed via differential antibody staining. The antiproliferative effect was evaluated using a β-galactosidase assay. Cytokine and VEGF levels were measured using ELISA and a cytometric bead array. ROS concentrations were quantified according to the intracellular peroxide-dependent oxidation. The involvement of VEGFR2 and ICAM-1 in the antiparasitic mechanism was investigated through docking simulations. Results: MjTX-II exhibited a high degree of purity in the biochemical and proteomic analyses. The MTT assay showed that MjTX-II did not reduce the viability of the BeWo cells. MjTX-II affected the surface of the parasites, decreased the number of intracellular parasites, and inhibited their intracellular proliferation. MjTX-II modulated the cellular environment by increasing the levels of IL-6, MIF, and ROS and reducing the levels of VEGF. The anti-T. gondii activity involved the modulation of the ROS and VEGF levels, as the addition of the ROS scavenger NAC or rVEGF reduced the antiprotozoal effect. Bioinformatic analyses revealed that MjTX-II is able to interact with the extracellular domain of VEGFR2 in the VEGF binding site, as well as ICAM-1, which was corroborated by the immunofluorescence analysis. Conclusions: Non-toxic concentrations of MjTX-II impaired T. gondii infection by increasing the ROS and VEGF levels in the host cells and may have involved interactions with ICAM-1 and VEGFR2, highlighting MjTX-II as prominent tool for the development of effective molecules against toxoplasmosis.

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in poultry feed, and Campylobacter jejuni is a major zoonotic pathogen in broilers. In a recent study, we demonstrated that DON not only increased C. jejuni colonization in the jejunum and cecum of infected birds but also elevated bacterial counts in internal organs. In contrast, its less toxic D metabolite, deepoxy–deoxynivalenol (DOM-1) significantly reduced the Campylobacter levels in vivo. These findings suggest that DON and DOM-1 may exert direct effects on C. jejuni growth dynamics.

The present study aimed to further explore this interaction in vitro through co-incubation and RNA-sequencing. Two C. jejuni strains were investigated: the reference strain NCTC 12744 and a field isolate (strain 1303) obtained from a broiler flock. Both strains (105 CFU/ml) were cultured in 96-well plates and incubated with either DON or DOM-1 (5 and 20 µg/mL) or without additives (as a control), under microaerophilic conditions at 41.5 °C. Bacterial counts were assessed at 6 h intervals from 24 to 48 h (24 h, 30 h, 36 h, 42 h, and 48 h).

Results showed that DON significantly promoted C. jejuni growth beginning at 30 h of incubation. Conversely, DOM-1 markedly reduced C. jejuni CFU counts, confirming the in vivo evidence of its potential to lower C. jejuni colonization in chickens. Additionally, transcriptomic profiling revealed that DON or DOM-1 modulate specific metabolic and regulatory pathways in C. jejuni. In particular, DON exposure upregulated genes related to energy metabolism and stress adaptation, while DOM-1 exposure led to the upregulation of pathways associated with growth inhibition.

These data are the first to demonstrate a direct, opposing influence of DON and its metabolite DOM-1 on C. jejuni growth. Our findings suggest that DON contamination in feed could promote Campylobacter proliferation in poultry, whereas DOM-1 may mitigate it. Understanding these interactions provides novel insights into how feed-derived toxins influence foodborne pathogens and could inform strategies to mitigate Campylobacter risk.

Mamba intestinal toxin (MIT) is a minor toxin component of Dendroaspis polylepis venom and has been shown to have potent effects on intestinal smooth muscle. Since the publication of these findings more than 25 years ago, there has been little further investigation into the toxin. We used chromatography to fractionate the venoms of all Dendroaspis species and identified fractions containing MIT in D. polylepis and D. angusticeps venoms, both of which were confirmed by mass spectrometry. We next profiled the activity of purified MITs using in vitro assays relevant to the neurotoxic effects of these venoms. Both DaMIT and DpMIT showed moderate inhibition of the human muscle-type nicotinic acetylcholine receptor (nAChR) and weak binding to a chimera of the human alpha-7 nAChR and acetylcholine-binding protein. No other venom fractions from D. angusticeps showed inhibitory activity on the human muscle-type nAChR, which suggests that MIT may be responsible for the post-synaptic neurotoxicity previously observed for this venom. DaMIT and DpMIT both demonstrated moderate inhibitory activity of human voltage-gated potassium channels, and surprisingly, both were capable of fully neutralising the enzymatic activity of human acetylcholinesterase. Our work demonstrates that MIT may target several proteins at the neuromuscular junction to contribute to the neurotoxic effects of D. polylepis and D. angusticeps venoms.

Introduction

Scorpion envenomation remains a significant public health issue in North Africa, particularly in Morocco, where it accounts for high morbidity and mortality, especially among children. As biological toxins, scorpion venoms can cause severe multisystemic complications, necessitating urgent medical attention. Understanding the clinical and biological impact of these envenomations is essential to improve health responses in affected regions.

Methods

This retrospective study analyzed 383 cases of pediatric scorpion stings recorded at the Regional Hospital Hassan II in Agadir (Souss Massa region) over a period of 9 years and 10 months, from January 2013 to October 2022. The patients were categorized into three age groups: under 1 year, 1–5 years, and over 5 years. Clinical, biological, and evolutionary data were collected and assessed to evaluate the severity and systemic effects of envenomation.

Results

Children under the age of 1 year exhibited the most severe clinical forms and the highest mortality rate. Clinical manifestations showed extensive toxic effects on the cardiovascular, neurological, and pulmonary systems, particularly in grade 2 and 3 cases. Alterations in vital signs (temperature, oxygen saturation, blood pressure, heart, and respiratory rates), biochemical markers (ASAT, ALAT, urea, creatinine, blood glucose), and hematological parameters revealed significant dysfunction in vital organs. A positive correlation was found between clinical evolution and factors such as age, symptom severity, and hemodynamic status.

Conclusions

This study highlights the serious health threat posed by scorpion venom in pediatric populations, especially infants. It underscores the need to strengthen prevention strategies, improve early medical management, and ensure the availability of effective immunotherapy. Scorpion envenomation represents a critical public health challenge in endemic areas and calls for targeted interventions to reduce toxin-related morbidity and mortality.

Introduction:

Scorpion envenomation is a major public health concern in North Africa, with Androctonus mauretanicus (Am), Androctonus australis hector (Aah), and Buthus occitanus (Bo) causing severe and often fatal cases. Am is the most dangerous and endemic species in Morocco. Due to the limited availability of effective antivenoms, treatment remains largely symptomatic. Understanding the pathophysiological mechanisms of venom action and improving therapeutic strategies are essential. This study aims to address this gap by developing and evaluating antivenoms targeting the main toxins involved in North African envenomations.

Methods:

The monovalent antivenom was produced by immunizing albino rabbits with Am venom collected from high-risk Moroccan regions. Neutralization potency was assessed in vivo using Swiss mice through LD₅₀ and ED₅₀ determinations. Histological and immunohistochemical analyses were conducted on vital organs (brain, heart, liver, lungs, kidneys) following administration of sublethal doses of Am, Aah, and Bo venoms. Both antivenoms (monovalent and Mexican polyvalent) were tested under similar conditions.

Results:

The Moroccan monovalent antivenom demonstrated strong specificity against Am and effective cross-neutralization of Aah and Bo venoms. Interestingly, while it showed superior efficacy against Am, the Mexican polyvalent antivenom was more effective in neutralizing the tissue damage induced by Bo and Aah. Histological evaluations confirmed a reduction in venom-induced lesions, particularly in cardiac and hepatic tissues, following antivenom administration four hours post-envenomation.

Conclusion:

This study underscores the critical role of antivenom as a specific and effective therapeutic tool in managing scorpion envenomations. The development of targeted antivenoms adapted to regional venom profiles enhances treatment outcomes and offers a promising path forward in combating scorpionism in Morocco and North Africa.

Fusarium fungi are among the most common moulds that can produce mycotoxins. Data on the occurrence of these mycotoxins, as well as their conjugated forms in cereals grown in Croatia, are still lacking, although several published studies have shown that Fusarium graminearum and (as a ZEN producent) and Fusarium culmorum (as a trichothecene producer) are the most widespread molds in Croatian crops. The aim of this study was to determine the prevalence of 16 Fusarium mycotoxins as well as their conjugated forms in maize (n=66), wheat (n=30), barley (n=17), triticale (n=12), and oats (n=12) harvested in three Croatian regions (East, North, and Central) which differ in climate during a one-year period. All samples were taken immediately after harvest and stored at -20 °C until liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The results revealed different contamination patterns between the analyzed cereals, except for wheat and triticale, which exhibited the same pattern. The most prevalent mycotoxin in wheat and triticale samples was deoxynivalenol (DON), at 73.3% and 91.7%, respectively, followed by deoxynivalenol-3-glucoside (DON-3G) and HT-2 toxin. In barley samples, the prevalence of DON and DON-3G was 55.6% and 44.4%, respectively; however, in contrast to wheat and triticale samples, ZEN-14 sulfate was detected as the third most prevalent mycotoxin. The analysis of maize samples indicated that this grain is more susceptible to fumonisin contamination, as fumonisin B1 and B2 were the most frequently occurring mycotoxins in these samples, with prevalence rates of 85.1% and 34.3%, respectively. The data obtained in this trial are pointing that the contamination patterns of wheat, triticale, and barley are similar but differ from the contamination pattern of maize, although further research is necessary to confirm these findings on a representative number of samples. These results could be used to establish a link between climatic conditions and the occurrence of mycotoxins.

Zearalenone (ZEA) is a naturally occurring foodborne mycotoxin and is of widespread interest because of its estrogen-like effects. However, the impact of the myco-estrogen ZEA on bone health remains incompletely understood. This study investigates the mechanisms underlying the effect of ZEA on bone health by establishing osteoporosis and osteoblast models in aged laying hens. ZEA exhibited deleterious effects on hens’ bone health by reducing femoral bone weight and bone mineral density (BMD), decreasing serum calcium (Ca) and phosphorus (P), elevating levels of alkaline phosphatase (ALP) and parathyroid hormone (PTH), diminishing the medullary bone micro-structural parameters (utilizing Micro-CT) and the proportion of trabeculae bone, and down-regulating the expression of osteogenic factors in bone. Interestingly, we found that hBMSCs differentiated towards adipocytes rather than osteoblasts in the ZEA micro-environment, which may be one of the reasons why ZEA causes bone damage. Subsequent experiments involving primary osteoblasts and hFob1.19 cell lines demonstrated that ZEA induced osteoblast apoptosis and impeded osteoblast proliferation. Transcriptome analysis revealed that ZEA primarily hindered osteoblast proliferation by activating the MAPK signaling pathway. Western blot identified that ZEA significantly increased ERK and P38 phosphorylation, with further confirmation through ERK and P38 phosphorylation antagonists. ZEA primarily targets the estrogen receptor (ER), specifically ERα, to activate the ERK/P38 MAPK signaling pathway. In summary, ZEA activates the ERK/P38 MAPK signaling pathway by targeting ERα, thereby inhibiting osteoblast proliferation and promoting osteoclast apoptosis, ultimately leading to decreased bone formation and increased osteoporosis.

Snakebite envenomation is a neglected tropical disease that affects between 4.5 and 5.4 million people annually. In South America, snakes of the Bothrops genus are the main medically relevant species involved in envenomations. Bothrops venom, rich in hemotoxic enzymes and toxins, frequently induces thrombocytopenia. Although it is known that venom toxins activate and remove platelets from circulation, the underlying mechanisms remain unclear. One proposed mechanism is platelet desialylation, induced by neuraminidases, which remove sialic acid from the platelet surface, promoting their clearance from circulation. Oseltamivir phosphate (Tamiflu®), an antiviral used against Influenza, inhibits viral neuraminidases and has been suggested as an adjuvant to block endogenous neuraminidase activity, potentially extending platelet lifespan.

This study investigated the effects of oseltamivir phosphate on thrombocytopenia induced by Bothrops jararaca venom (BjV) in Swiss mice (IACUC Instituto Butantan, protocol no. 7416200723). Animals were divided into four groups, receiving intraperitoneal injections of saline (SAL) or oseltamivir phosphate (OSELT), followed by subcutaneous administration of SAL or BjV. Blood samples were collected 3 and 6 hours after envenomation, and hematological parameters were analyzed using an automated cell counter. Data was assessed using one-way ANOVA and post hoc tests.
Envenomed groups exhibited significant thrombocytopenia, which was not reversed by oseltamivir. In healthy animals, the drug did not alter platelet levels. Lymphocytopenia was observed in BjV-treated groups, along with an increase in leukocyte count, including a mild elevation in the OSELT+SAL group. Red blood cell counts and hematocrit levels remained stable.
In conclusion, exposure to BjV led to thrombocytopenia, lymphocytopenia, and leukocytosis—all of which were not reversed by Oseltamivir treatment. While the drug appeared neutral in healthy animals, it was not effective in preventing the acute hematological effects of the venom when administered in isolation.

Zearalenone (ZEN), a mycotoxin commonly found in cereal crops and foods, induces testicular damage and disrupts gut microbial composition, revealing a critical connection between gut microbes and the male reproductive system. Curcumin (CUR), a bioactive compound derived from ginger, is known to enhance intestinal microecological balance and exhibit anti-inflammatory properties. This study aimed to investigate the mechanism by which CUR alleviates ZEN-induced reductions in sperm quality through the modulation of the gut microbe–testis axis. Forty-eight 6-week-old Balb/c male mice were randomly assigned to four treatment groups: control (CON), CUR (200 mg/kg body weight CUR), ZEN (40 mg/kg body weight ZEN), and ZEN + CUR (200 mg/kg CUR + 40 mg/kg ZEN). The experiment lasted 28 days. CUR was found to mitigate ZEN-induced reductions in testosterone levels, testicular structural damage, and disrupted spermatogenesis. ZEN exposure altered gut microbial composition, increasing the abundance of Prevotella and decreasing Lactobacillus. CUR counteracted these effects and reduced the ZEN-induced activation of IL-17A-TNF-α signaling pathway proteins. In conclusion, ZEN induces testicular inflammation and reduced sperm quality by lowering testosterone levels and disrupting gut microbial balance, which drives the testicular IL-17A signaling pathway. CUR alleviates ZEN-induced testicular inflammation and sperm quality reduction by restoring beneficial gut microbes and testosterone levels.

Pseudomonas aeruginosa is a common nosocomial pathogen that causes significant morbidity and mortality, especially among immunocompromised individuals. Its capacity to develop antibiotic resistance presents a significant obstacle in treatment. It generates various extracellular toxins and virulence factors, including alkaline protease, elastase, and phospholipase C, which destroy tissues and encourage bacterial invasion. Other toxins include pyocyanin, a phenazine pigment that may damage membrane proteins, produce oxidative stress, and cause substantial tissue damage. To address this, alternative methods that target virulence factors and toxin production are being investigated. Nanotechnology has emerged as a viable technique for reducing the virulence of P. aeruginosa by decreasing the production of toxins and other pathogenic components. In this study, we manufactured gold (AuNPs), silver (AgNPs), and zinc oxide nanoparticles (ZnONPs) using lactic acid bacteria, specifically Leuconostoc sp. strain C2 and Lactiplantibacillus sp. strain C1. The nanoparticles produced were labeled as C1-AuNPs, C1-AgNPs, C2-AuNPs, and C2-ZnONPs. The nanoparticles exhibited antibacterial activity against P. aeruginosa, with MICs of 1024 µg/mL for C1-AuNPs, 32 µg/mL for C1-AgNPs, and >2048 µg/mL for C2-AuNPs and C2-ZnONPs. C1-AuNPs, C1-AgNPs, C2-AuNPs, and C2-ZnONPs decrease pyocyanin toxin production by 57.75% (at 512 μg/mL), 26.07% (at 16 μg/mL), 71.07% (at 1024 µg/mL), and 82.15% (at 1024 µg/mL). Furthermore, at the sub-MIC level, these nanoparticles limit protease activity in a concentration-dependent manner. The current findings demonstrated that inhibiting the LAB-inspired nanoparticles is a promising technique for reducing their virulence and pathogenicity.

Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea grant funded by the Ministry of Education (RS-2023-00241461).