Measurement of hepatic glucose (18F-fluorodeoxyglucose) uptake with positron emission tomography-magnetic resonance imaging in fumonisin B intoxicated rabbit bucks.

Rabbit bucks (bodyweight 5 kg) underwent dietary intoxication with fumonisin B series mycotoxins (FB1 + FB2 + FB3, 15 mg/kg diet) for 14 days to test the applicability of positron emission tomography-magnetic resonance (PET MR) hybrid imaging in characterizing experimentally induced mild hepatotoxicosis. 18F-fluorodeoxyglucose (18F-FDG) radiotracer-aided imaging was performed before and after FBs administration on identical animals, and at both time points, blood was sampled for haematology and clinical chemistry. Kinetic PET image analysis revealed time-activity curves with uptake maxima below 1 min in the liver, renal cortex, portal vein, lung and coarctatio aortae. In the frame of static PET image analysis, based on the standardized uptake value (SUV), the so-called metabolic liver volume (MLV, liver volume defined by over 0.9 × average liver SUV) and the total liver glycolysis (TLG, MLV multiplied by the SUVmean) were calculated. Mycotoxicosis increased total liver glycolysis (p < 0.04) after 14 days and liver tissue TLG inhomogeneity was minimal. Pearson correlation between TLG and alkaline phosphatase (ALP) was positive (0.515), while negative with LDH and AST (- 0.721 and - 0.491, respectively). Results indicate a slight hepatic mycotoxin effect and significantly increased glucose uptake intensity, which has been sensitively detected with molecular imaging (18F-FDG PET MRI) in the rabbit model.

Field validation as a means for continual monitoring of approved test kit's fitness for purpose in the commercial market.

Testing accuracy of a chemical contaminant requires use of a testing platform that conforms to validation criteria outlined in quality literature and standards. This study explores the application of commercial field data measured by qualified analysts using a United States Department of Agriculture - Federal Grain Inspection Service approved kit for measuring fumonisin in maize to augment method validation procedures. Analysts from seven grain testing facilities were qualified in official USDA sampling, sample preparation, and testing methodology using the Charm LF-FUMQ-WETS5. A duplicate sample was tested in the Office of the Texas State Chemist (OTSC) laboratory using UPLC-MS-MS. Data were subject to four statistical techniques using continuous and categorical methodology. This approach enabled researchers to explore if a single test or multiple comparisons were best suited to assess a field kit's fitness for purpose across facility, toxin level, and year. The study concluded that a paired t-test and correlation analysis provided a quick and meaningful evaluation of kit performance. The correct placement of samples within the correct bin (violative versus non-violative) aligns well with market forces and regulatory compliance. The results of this study also provide a useful tool to assess all field kits' performance at the beginning of the harvest season and subsequent years. The combination of statistical techniques presented in this research is an important tool in assessing mycotoxin field test kits fitness for purpose and represents a key step in a continuous improvement-quality systems process meant to protect the feed and food supply.

Fumonisin B1 induces endoplasmic reticulum damage and inflammation by activating the NXR response and disrupting the normal CYP450 system, leading to liver damage in juvenile quail.

Fumonisin B1 (FB1) is a mycotoxin affecting animal health through the food chain and has been closely associated with several diseases such as pulmonary edema in pigs and diarrhea in poultry. FB1 is mainly metabolized in the liver. Although a few studies have shown that FB1 causes liver damage, the molecular mechanism of liver damage is unclear. This study aimed to evaluate the role of liver damage, nuclear xenobiotic receptor (NXR) response and cytochrome P450 (CYP450)-mediated defense response during FB1 exposure. A total of 120 young quails were equally divided into two groups (control and FB1 groups). The quails in the control group were fed on a normal diet, while those in the FB1 group were fed on a quail diet containing 30 mg/kg for 42 days. Histopathological and ultrastructural changes in the liver, biochemical parameters, inflammatory factors, endoplasmic reticulum (ER) factors, NXR response and CYP450 cluster system and other related genes were examined at 14 days, 28 days and 42 days. The results showed that FB1 exposure impaired the metabolic function and caused liver injury. FB1 caused ER stress and decreased adenosine triphosphatease activity, induced the expression of inflammation-related genes such as interleukin 6 and nuclear factor kappa-B, and promoted inflammation. In addition, FB1 disrupted the expression of multiple CYP450 isoforms by activating nuclear xenobiotic receptors (NXRs). The present study confirms that FB1 exposure disturbs the homeostasis of cytochrome P450 systems (CYP450s) in quail liver by activating NXR responses and thereby causing liver damage. This study's findings provide insight into the molecular mechanisms of FB1-induced hepatotoxicity.

Mechanism of ceramide synthase inhibition by fumonisin B1.

Ceramide synthases (CerSs) play crucial roles in sphingolipid metabolism and have emerged as promising drug targets for metabolic diseases, cancers, and antifungal therapy. However, the therapeutic targeting of CerSs has been hindered by a limited understanding of their inhibition mechanisms by small molecules. Fumonisin B1 (FB1) has been extensively studied as a potent inhibitor of eukaryotic CerSs. In this study, we characterize the inhibition mechanism of FB1 on yeast CerS (yCerS) and determine the structures of both FB1-bound and N-acyl-FB1-bound yCerS. Through our structural analysis and the observation of N-acylation of FB1 by yCerS, we propose a potential ping-pong catalytic mechanism for FB1 N-acylation by yCerS. Lastly, we demonstrate that FB1 exhibits lower binding affinity for yCerS compared to the C26- coenzyme A (CoA) substrate, suggesting that the potent inhibitory effect of FB1 on yCerS may primarily result from the N-acyl-FB1 catalyzed by yCerS, rather than through direct binding of FB1.

Production of Nanocellulose from Sugarcane Bagasse and Development of Nanocellulose Conjugated with Polylysine for Fumonisin B1 Toxicity Absorption.

The present study aimed to extract nanocellulose (NC) from sugarcane bagasse agricultural waste through a chemical method (sulfuric acid hydrolysis and ultrasonication). Subsequently, the nanocellulose product was conjugated with polylysine (NC-PL) and assessed for its efficacy in reducing the toxicity of Fumonisin B1 (FB1), a mycotoxin produced by fungi commonly found in corn, wheat, and other grains. Experimental results confirmed the successful conjugation of NC and PL, as evidenced by FTIR peaks at 1635 and 1625 cm-1 indicating amide I and amide II vibrations in polylysine (PL). SEM analysis revealed a larger size due to PL coating, consistent with DLS results showing the increased size and positive charge (38.0 mV) on the NC-PL surface. Moreover, the effect of FB1 adsorption by NC and NC-PL was evaluated at various concentrations (0-200,000 µg/mL). NC-PL demonstrated the ability to adsorb FB1 at concentrations of 2000, 20,000, and 200,000 µg/mL, with adsorption efficiencies of 94.4-100%. Human hepatocellular carcinoma (HepG2) cells were utilized to assess NC and NC-PL cytotoxic effects. This result is a preliminary step towards standardizing results for future studies on their application as novel FB1 binders in food, food packaging, and functional feeds.

Efficacy of Aflatoxin B1 and Fumonisin B1 Adsorption by Maize, Wheat, and Oat Bran.

Mycotoxins, especially aflatoxin B1 (AFB1) and fumonisin B1 (FMB1), are common contaminants in cereal-based foods. Instances of contamination are predicted to increase due to the current challenges induced by climate change. Despite the health benefits of whole grains, the presence of mycotoxins in bran remains a concern. Nonetheless, previous research indicates that wheat bran can adsorb mutagens. Therefore, this study investigated the capacity of maize, wheat, and oat brans to adsorb AFB1 and FMB1 under varying in vitro conditions, including pH, binding time, temperature, particle size, and the amount of bran utilized. Maize bran demonstrated a high AFB1 adsorption capacity (>78%) compared to wheat and oat brans. However, FMB1 was not adsorbed by the brans, possibly due to its hydrophilic nature. Lower temperature (≤25 °C) enhanced AFB1 adsorption efficacy in wheat and oat bran, while for maize bran, the highest adsorption occurred at 37 °C. A linear model following Henry's law best explained AFB1 adsorption by the brans. Further studies identified the pericarp layer of bran as the primary site of AFB1 adsorption, with the initial liquid volume being a critical factor. The study concludes that bran could potentially act as an effective bioadsorbent. Further research is essential to confirm the adsorption efficacy and the bioavailability of AFB1 through in vivo experiments.

Oral Exposure to Low Concentration of Fumonisin B2, but Not Fumonisin B1, Significantly Exacerbates the Pathophysiology of Imiquimod-Induced Psoriasis in Mice.

This study aimed to determine whether oral fumonisin exposure contributes to the development of psoriasis. Oral administration of fumonisin B1 (FB1, 0.1 mg/kg) or fumonisin B2 (FB2, 0.1 mg/kg) was conducted for 10 days, in addition to the induction of psoriatic symptoms through topical application of 5% imiquimod cream from day 6 to day 10 (5 days) in female BALB/c mice. The results demonstrated that oral administration of FB2 significantly exacerbated psoriatic symptoms, including skin thickness, itching behavior, transepidermal water loss, immune cell infiltration in the dermis, and proinflammatory cytokine production. However, no changes were observed following exposure to FB1. Our results confirm that oral exposure to FB2 adversely affects the pathogenesis of psoriasis by increasing skin thickness and impairing barrier function.

Involvement of aryl hydrocarbon receptor in the aflatoxin B1 and fumonisin B1 effects on in vitro differentiation of murine regulatory-T and Th17 cells.

Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely found as cereal contaminants, and their co-consumption is associated with liver cancer. Both are immunotoxic, but their interactions have been little studied. This work was aimed to evaluate in mouse spleen mononuclear cells (SMC) the effects of the exposure to AFB1 (5-50 µM), FB1 (25-250 µM), and AFB1-FB1 mixtures (MIX) on the in vitro differentiation of regulatory T cells (Treg and Tr1-like) and Th17 cells, as well as elucidate the contribution of aryl hydrocarbon receptor (Ahr) in such effects. AFB1 and mainly MIX induced cytotoxicity in activated CD4 cells via Ahr signaling. AFB1 (5 µM) increased the Treg cell differentiation, but its combination with FB1 (25 µM) also reduced Th17 cell expansion by Ahr-dependent mechanisms. Therefore, this mixture could enhance the Treg/Th17 cell ratio and favor immunosuppression and escape from tumor immunosurveillance to a greater extent than individual mycotoxins. Whereas, AFB1-FB1 mixtures at medium-high doses inhibited the Tr1-like cell expansion induced by the individual mycotoxins and affected Treg and Th17 cell differentiation in Ahr-independent and dependent manners, respectively, which could alter anti-inflammatory and Th17 immune responses. Moreover, individual FB1 altered regulatory T and Th17 cell development independently of Ahr. In conclusion, AFB1 and FB1 interact by modifying Ahr signaling, which is involved in the immunotoxicity as well as in the alteration of the differentiation of Treg, Tr1-like, and Th17 cells induced by AFB1-FB1 mixtures. Therefore, Ahr is implicated in the regulation of the anti- and pro-inflammatory responses caused by the combination of AFB1 and FB1.

Enhancing maize safety: the role of co-regulation as a regulatory strategy to manage fumonisin risk.

This study explores the implementation of the One Sample Strategy (OSS), a co-regulation program aimed at managing mycotoxin risk in Texas maize. Fumonisin-contaminated cereals and oilseeds that contain greater than 5 mg kg-1 of the toxin (B1, B2, and B3) are a risk for equids and rabbits, and levels greater than 60 mg kg-1 are a risk to ruminants. The OSS, previously successful in managing aflatoxin risk in Texas maize, was evaluated for its effectiveness in handling fumonisin risk in maize, specifically as it relates to ruminants. In 2017, 25 analysts across seven firms qualified to participate in the program. To ensure greater accuracy in testing, working control samples were provided to the participating OSS firms with the requirement that their results fall within +/- 20% of the target concentration. Ninety-four percent of the working controls met this specification. The capability to grind maize to the OSS prescribed particle size was met by 100% of participants. To verify testing accuracy, file samples collected from each OSS firm were analysed by UPLC-MS/MS. The 177 fumonisin verification samples analysed by Office of the Texas State Chemist (OTSC) were correlated (r = 0.93) with co-regulation laboratories. Results were plotted in an operating curve to depict type I and type II errors. Error analysis revealed a type I error rate of 13% and type II error rate of 2% for the 5 mg kg-1 guidance level, and 6% and 8%, respectively, for the 60 mg kg-1 guidance level. For 2017, 994 official reports of analysis for fumonisin in whole maize in the Texas High Plains were issued by the seven laboratories that employed 25 OTSC-credentialed analysts. The OSS co-regulation program, supported by a quality systems approach and government regulations, has proven effective in managing fumonisin risk in Texas maize, enhancing both market confidence and livestock safety.

Validamycin A Inhibited FB1 Biosynthesis by the Target FvNth in Fusarium verticillioides.

Validamycin A (VMA) is an antifungal antibiotic derived from Streptomyces hygroscopicus commonly used in plant disease management. Surprisingly, VMA was discovered to impede the production of fumonisin B1 (FB1) in agricultural settings. However, the specific target of VMA in Fusarium verticillioides remained unclear. To unravel the molecular mechanism of VMA, ultrastructural observations unveiled damage to mitochondrial membranes. Trehalase (FvNth) was pinpointed as the target of VMA by utilizing a 3D-printed surface plasmon resonance sensor. Molecular docking identified Trp285, Arg447, Asp452, and Phe665 as the binding sites between VMA and FvNth. A ΔFvnth mutant lacking amino acids 250-670 was engineered through homologous recombination. Transcriptome analysis indicated that samples treated with VMA and ΔFvnth displayed similar expression patterns, particularly in the suppression of the FUM gene cluster. VMA treatment resulted in reduced trehalase and ATPase activity as well as diminished production of glucose, pyruvic acid, and acetyl-CoA. Conversely, these effects were absent in samples treated with ΔFvnth. This research proposes that VMA hinders acetyl-CoA synthesis by trehalase, thereby suppressing the FB1 biosynthesis. These findings present a novel target for the development of mycotoxin control agents.

Mechanism of Fumonisin Self-Resistance: Fusarium verticillioides Contains Four Fumonisin B1-Insensitive-Ceramide Synthases.

Fusarium verticillioides produces fumonisins, which are mycotoxins inhibiting sphingolipid biosynthesis in humans, animals, and other eukaryotes. Fumonisins are presumed virulence factors of plant pathogens, but may also play a role in interactions between competing fungi. We observed higher resistance to added fumonisin B1 (FB1) in fumonisin-producing Fusarium verticillioides than in nonproducing F. graminearum, and likewise between isolates of Aspergillus and Alternaria differing in production of sphinganine-analog toxins. It has been reported that in F. verticillioides, ceramide synthase encoded in the fumonisin biosynthetic gene cluster is responsible for self-resistance. We reinvestigated the role of FUM17 and FUM18 by generating a double mutant strain in a fum1 background. Nearly unchanged resistance to added FB1 was observed compared to the parental fum1 strain. A recently developed fumonisin-sensitive baker's yeast strain allowed for the testing of candidate ceramide synthases by heterologous expression. The overexpression of the yeast LAC1 gene, but not LAG1, increased fumonisin resistance. High-level resistance was conferred by FUM18, but not by FUM17. Likewise, strong resistance to FB1 was caused by overexpression of the presumed F. verticillioides "housekeeping" ceramide synthases CER1, CER2, and CER3, located outside the fumonisin cluster, indicating that F. verticillioides possesses a redundant set of insensitive targets as a self-resistance mechanism.

Mycotoxin contamination in organic and conventional cereal grain and products: A systematic literature review and meta-analysis.

There is still considerable controversy about the relative risk of mycotoxin exposure associated with the consumption of organic and conventional cereals. Using validated protocols, we carried out a systematic literature review and meta-analyses of data on the incidence and concentrations of mycotoxins produced by Fusarium, Claviceps, Penicillium, and Aspergillus species in organic and conventional cereal grains/products. The standard weighted meta-analysis of concentration data detected a significant effect of production system (organic vs. conventional) only for the Fusarium mycotoxins deoxynivalenol, with concentrations ∼50% higher in conventional than organic cereal grains/products (p < 0.0001). Weighted meta-analyses of incidence data and unweighted meta-analyses of concentration data also detected small, but significant effects of production system on the incidence and/or concentrations of T-2/HT-2 toxins, zearalenone, enniatin, beauvericin, ochratoxin A (OTA), and aflatoxins. Multilevel meta-analyses identified climatic conditions, cereal species, study type, and analytical methods used as important confounding factors for the effects of production system. Overall, results from this study suggest that (i) Fusarium mycotoxin contamination decreased between the 1990s and 2020, (ii) contamination levels are similar in organic and conventional cereals used for human consumption, and (iii) maintaining OTA concentrations below the maximum contamination levels (3.0 µg/kg) set by the EU remains a major challenge.

Exposure to a Combination of Fusarium Mycotoxins Leads to Lipid Peroxidation and Influences Antioxidant Defenses, Fatty Acid Composition of Phospholipids, and Renal Histology in Laying Hens.

The effects of combined short-term (3 days) exposure to Fusarium mycotoxins at both the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON/3-AcDON/15-AcDON: 5 mg/kg; FB1: 20 mg/kg) and twice the dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg/kg, and FB1: 40 mg/kg feed) on the kidneys of laying hens were examined. Our study aimed to investigate how these mycotoxins interacted with membrane lipid fatty acid (FA) composition and lipid peroxidation processes. It was observed that the levels of conjugated dienes and trienes were higher than the control in the low-mix group on day 3, and malondialdehyde concentration was higher on days 2 and 3. The proportion of phospholipid (PL) FAs showed that saturated and monounsaturated FAs increased. Still, both n3 and n6 polyunsaturated FAs decreased significantly on day 2 of exposure in the high-mix group. Among the n3 FAs, the level of docosahexaenoic (C22:6 n3) and among n6 FAs, arachidonic (C20:4 n6) acids decreased mainly on day 2 in the high-mix group. The results suggest that the combined exposure to Fusarium mycotoxins induced lipid peroxidation in the kidneys of laying hens, which resulted in marked changes in the PL FA profile. Histological examination revealed time- and dose-dependent increases as consequences of mycotoxin exposure.

Gold nanoparticles-doped MXene heterostructure for ultrasensitive electrochemical detection of fumonisin B1 and ampicillin.

Early transition metal carbides (MXene) hybridized by precious metals open a door for innovative electrochemical biosensing device design. Herein, we present a facile one-pot synthesis of gold nanoparticles (AuNPs)-doped two-dimensional (2D) titanium carbide MXene nanoflakes (Ti3C2Tx/Au). Ti3C2Tx MXene exhibits high electrical conductivity and yields synergistic signal amplification in conjunction with AuNPs leading to excellent electrochemical performance. Thus Ti3C2Tx/Au hybrid nanostructure can be used as an electrode platform for the electrochemical analysis of various targets. We used screen-printed electrodes modified with the Ti3C2Tx/Au electrode and functionalized with different biorecognition elements to detect and quantify an antibiotic, ampicillin (AMP), and a mycotoxin, fumonisin B1 (FB1). The ultralow limits of detection of 2.284 pM and 1.617 pg.mL-1, which we achieved respectively for AMP and FB1 are far lower than their corresponding maximum residue limits of 2.8 nM in milk and 2 to 4 mg kg-1 in corn products for human consumption set by the United States Food and Drug Administration. Additionally, the linear range of detection and quantification of AMP and FB1 were, respectively, 10 pM to 500 nM and 10 pg mL-1 to 1 µg mL-1. The unique structure and excellent electrochemical performance of Ti3C2Tx/Au nanocomposite suggest that it is highly suitable for anchoring biorecognition entities such as antibodies and oligonucleotides for monitoring various deleterious contaminants in agri-food products.

Encapsulation of Apium graveolens essential oil into chitosan nanobiopolymer for protection of stored rice against Fusarium verticillioides and fumonisins contamination.

The present investigation entails the encapsulation of Apium graveolens essential oil into chitosan nanobiopolymer (AGEO-Ne) and assessment of its efficacy against Fusarium verticillioides contamination and fumonisins biosynthesis in stored rice (Oryza sativa L.) samples. The AGEO was encapsulated through ionic gelation process and characterized by scanning electron microscopy (SEM), Dynamic light scattering (DLS), X-ray diffractometry (XRD), and Fourier transform infrared spectroscopy (FTIR) analyses. The AGEO exhibited bi-phasic delivery pattern from chitosan matrix. The AGEO caused complete inhibition of F. verticillioides growth at 1.2 µL/mL, while fumonisin B1 (FB1) and B2 (FB2) biosynthesis at 1.2 and 1.0 µL/mL, respectively. On the other hand, nanoencapsulated AGEO (AGEO-Ne) exhibited improved efficacy, caused complete inhibition of fungal growth at 0.8 µL/mL, and FB1 and FB2 production at 0.8 and 0.6 µL/mL, respectively. AGEO-Ne caused 100 % inhibition of ergosterol synthesis at 0.8 µL/mL and exhibited greater efflux of Ca2+, Mg2+, K+ ions (18.99, 21.63, and 25.38 mg/L) as well as 260 and 280 nm absorbing materials from exposed fungal cells. The in silico interaction of granyl acetate and linalyl acetate with FUM 21 protein validated the molecular mechanism for inhibition of FB1 and FB2 biosynthesis. Further, improvement in antioxidant activity of AGEO-Ne was observed after encapsulation with IC50 values of 12.08 and 6.40 µL/mL against DPPH and ABTS radicals, respectively. During in situ investigation, AGEO caused 82.09 and 86.32 % protection of rice against F. verticillioides contamination in inoculated and uninoculated rice samples, respectively, while AGEO-Ne exhibited 100 % protection of fumigated rice samples against F. verticillioides proliferation as well as FB1 and FB2 contamination. The AGEO-Ne also caused better retardation of lipid peroxidation (41.35 and 37.52 µM/g FW malondialdehyde in inoculated and uninoculated treatment) and acceptable organoleptic properties in rice samples, which strengthen its application as plant based novel preservative in food and agricultural industries.

Mild endoplasmic reticulum stress alleviates FB1-triggered intestinal pyroptosis via the Sec62-PERK pathway.

Fumonisin B1 (FB1), a water-soluble mycotoxin released by Fusarium moniliforme Sheld, is widely present in corn and its derivative products, and seriously endangers human life and health. Recent studies have reported that FB1 can lead to pyroptosis, however, the mechanisms by which FB1-induced pyroptosis remain indistinct. In the present study, we aim to investigate the mechanisms of pyroptosis in intestinal porcine epithelial cells (IPEC-J2) and the relationship between FB1-induced endoplasmic reticulum stress (ERS) and pyroptosis. Our experimental results showed that the pyroptosis protein indicators in IPEC-J2 were significantly increased after exposure to FB1. The ERS markers, including glucose-regulated Protein 78 (GRP78), PKR-like ER kinase protein (PERK), and preprotein translocation factor (Sec62) were also significantly increased. Using small interfering RNA silencing of PERK or Sec62, the results demonstrated that upregulation of Sec62 activates the PERK pathway, and activation of the PERK signaling pathway is upstream of FB1-induced pyroptosis. After using the ERS inhibitor 4-PBA reduced the FB1-triggered intestinal injury by the Sec62-PERK pathway. In conclusion, we found that FB1 induced pyroptosis by upregulating Sec62 to activate the PERK pathway, and mild ERS alleviates FB1-triggered damage. It all boils down to one fact, the study provides a new perspective for further, and improving the toxicological mechanism of FB1.

Self-powered photoelectrochemical aptasensor for fumonisin B1 detection based on a Z-scheme ZnIn2S4/WO3 photoanode.

The incidence of esophageal cancer is positively associated with fumonisin contamination. It is necessary to develop methods for the rapid detection of fumonisins. In this work, a self-powered photoelectrochemical aptamer sensor based on ZnIn2S4/WO3 photoanode and Au@W-Co3O4 photocathode is proposed for the sensitive detection of fumonisin B1 (FB1). Among them, under visible light irradiation, the Z-type heterostructure of ZnIn2S4/WO3 acts as a photoanode to improve the electron transfer rate, which contributes to the enhancement of the photocathode signal and lays the foundation for a wider detection range. The Au@W-Co3O4 photocathode as a sensing interface reduces the probability of false positives (comparison of anode sensing platforms). The PEC sensor has a good working performance in the detection range (10 pg/mL-1000 ng/mL) with a detection limit of 2.7 pg/mL (S/N = 3). In addition, the sensor offers good selectivity, stability and excellent recoveries in real sample analysis. This work is expected to play a role in the field of analyzing environmental toxins.

Mitophagy-regulated Necroptosis plays a vital role in the nephrotoxicity of Fumonisin B1 in vivo and in vitro.

Fumonisin B1 (FB1), one of the most widely distributed mycotoxins found in grains and feeds as contaminants, affects many organs including the kidney once ingested. However, the nephrotoxicity of FB1 remains to be further uncovered. The connection between necroptosis and nephrotoxicity of FB1 has been investigated in this study. The results showed that mice exposed to high doses of FB1 (2.25 mg/kg b.w.) developed kidney damage, with significant increases in proinflammatory cytokines (Il-6, Il-1ß), kidney injury-related markers (Ngal, Ntn-1), and gene expressions linked to necroptosis (Ripk1, Ripk3, Mlkl). The concentration-dependent damage effects of FB1 on PK-15 cells contain cytotoxicity, cellular inflammatory response, and necroptosis. These FB1-induced effects can be neutralized by pretreatment with the necroptosis inhibitor Nec-1. Additionally, FB1 caused mitochondrial damage and mitophagy in vivo and in vitro, whereas Mdivi-1, a mitophagy inhibitor, prevented these effects on PK-15 cells as well as, more crucially, necroptosis. In conclusion, the RIPK1/RIPK3/MLKL signal route of necroptosis, which may be controlled by mitophagy, mediated nephrotoxicity of FB1. Our findings clarify the underlying molecular pathways of FB1-induced nephrotoxicity.

Magnolol ameliorates fumonisin B1-induced oxidative damage and lipid metabolism dysfunction in astrocyte-like C6 cells.

The neurotoxicity of fumonisin B1 (FB1), a commonly detected mycotoxin in crops and the environment, has attracted considerable attention in recent years. However, no effective method for eliminating FB1 completely exists due to the thermal stability and water solubility of this mycotoxin. Magnolol (MAG) is a neolignane with antioxidative and neuroprotective effects. It has been applied in neurotoxicity treatment. However, the application of MAG to attenuate FB1-induced toxicity has not been reported. This study explored the protective mechanism of MAG against FB1-induced damage in C6 cells through antioxidant and lipid metabolism modulation. Results showed that exposure to 15 µM FB1 caused oxidative stress by changing the levels of malondialdehyde, reactive oxygen species, total superoxide dismutase, catalase, and total glutathione. These changes were reversed by MAG addition, especially at the concentration of 80 µM. The protective effects of MAG were further confirmed by the reduction in the phosphorylation levels of proteins in the MAPK signaling pathway. Lipidomics analysis identified 263 lipids, which belong to 24 lipid classes. Among all of the identified lipids, triglycerides (TGs), diglycerides (DGs), phosphatidylcholines (PCs), wax monoesters (WEs), Cers, and phosphatidylethanolamines (PEs) were major categories. Moreover, nine categories of lipids showed the opposite change trend in the FB1 exposure and MAG 80 groups. A further investigation of the 34 co-occurring differential lipids with remarkable changes (P value < 0.05 and VIP value > 1) in the control, FB1 exposure, and MAG 80 groups was performed. Therein, nine lipids (PCs, LPCs, and SM) were screened out as potential biomarkers to reveal the cytoprotective effects of MAG. This work is the first to investigate the rescue mechanism of MAG in FB1-induced cytotoxicity. The obtained results may expand the application of MAG to alleviate the toxicity of mycotoxins.

Insights from modelling sixteen years of climatic and fumonisin patterns in maize in South Africa.

Mycotoxin contamination of agricultural commodities is a global public health problem that has remained elusive to various mitigation approaches, particularly in developing countries. Climate change and its impact exacerbates South Africa's vulnerability to mycotoxin contamination, and significantly threatens its's food systems, public health, and agro-economic development. Herein we analyse sixteen years (2005/2006-2020/2021) of annual national meteorological data on South Africa which reveals both systematic and erratic variability in critical climatic factors known to influence mycotoxin contamination in crops. Within the same study period, data on fumonisin (FB) monitoring show clear climate-dependent trends. The strongest positive warming trend is observed between 2018/2019 and 2019/2020 (0.51 °C/year), and a strong positive correlation is likewise established between FB contamination and temperature (r ranging from 0.6 to 0.9). Four machine learning models, viz support vector machines, eXtreme gradient boosting, random forest, and orthogonal partial least squares, are generalized on the historical data with suitable performance (RMSE as low as 0.00). All the adopted models are able to predict future FB contamination patterns with reasonable precision (R2 ranging from 0.34 to 1.00). The most important model feature for predicting average FB contamination (YA) is the historical pattern of average FB contamination in maize within the region (ΣFBs_avg). The two most significant features in modelling maximum FB contamination (YM) are minimum temperature from the CMIP6 data (Pro_tempMIN) and observed precipitation from the CRU data (O_prep). Our study provides strong evidence of the impact of climate change on FB in South Africa and reiterates the significance of machine learning modelling in predicting mycotoxin contamination in light of changing climatic conditions, which could facilitate early warnings and the adoption of relevant mitigation measures that could help in mycotoxin risk management and control.