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NAR Molecular Medicine Apr 2024Increased risk for the development of hepatocellular carcinoma (HCC) is driven by a number of etiological factors including hepatitis viral infection and dietary...
Increased risk for the development of hepatocellular carcinoma (HCC) is driven by a number of etiological factors including hepatitis viral infection and dietary exposures to foods contaminated with aflatoxin-producing molds. Intracellular metabolic activation of aflatoxin B (AFB) to a reactive epoxide generates highly mutagenic AFB-Fapy-dG adducts. Previously, we demonstrated that repair of AFB-Fapy-dG adducts can be initiated by the DNA glycosylase NEIL1 and that male mice were significantly more susceptible to AFB-induced HCC relative to wild-type mice. To investigate the mechanisms underlying this enhanced carcinogenesis, WT and mice were challenged with a single, 4 mg/kg dose of AFB and frequencies and spectra of mutations were analyzed in liver DNAs 2.5 months post-injection using duplex sequencing. The analyses of DNAs from AFB-challenged mice revealed highly elevated mutation frequencies in the nuclear genomes of both males and females, but not the mitochondrial genomes. In both WT and mice, mutation spectra were highly similar to the AFB-specific COSMIC signature SBS24. Relative to wild-type, the NEIL1 deficiency increased AFB-induced mutagenesis with concomitant elevated HCCs in male mice. Our data establish a critical role of NEIL1 in limiting AFB-induced mutagenesis and ultimately carcinogenesis.
PubMed: 38779538
DOI: 10.1093/narmme/ugae006 -
Ecotoxicology and Environmental Safety Jul 2024Over the past few years, there has been growing interest in the ability of insect larvae to convert various organic side-streams containing mycotoxins into insect...
Over the past few years, there has been growing interest in the ability of insect larvae to convert various organic side-streams containing mycotoxins into insect biomass that can be used as animal feed. Various studies have examined the effects of exposure to aflatoxin B (AFB) on a variety of insect species, including the larvae of the black soldier fly (BSFL; Hermetia illucens L.; Diptera: Stratiomyidae) and the housefly (HFL; Musca domestica L.; Diptera: Muscidae). Most of these studies demonstrated that AFB degradation takes place, either enzymatic and/or non-enzymatic. The possible role of feed substrate microorganisms (MOs) in this process has thus far not been investigated. The main objective of this study was therefore to investigate whether biotransformation of AFB occurred and whether it is caused by insect-enzymes and/or by microbial enzymes of MOs in the feed substrate. In order to investigate this, sterile and non-sterile feed substrates were spiked with AFB and incubated either with or without insect larvae (BSFL or HFL). The AFB concentration was determined via LC-MS/MS analyses and recorded over time. Approximately 50% of the initially present AFB was recovered in the treatment involving BSFL, which was comparable to the treatment without BSFL (60%). Similar patterns were observed for HFL. The molar mass balance of AFB for the sterile feed substrates with BSFL and HFL was 73% and 78%, respectively. We could not establish whether non-enzymatic degradation of AFB in the feed substrates occurred. The results showed that both BSFL and substrate-specific MOs play a role in the biotransformation of AFB as well as in conversion of AFB into aflatoxin P and aflatoxicol, respectively. In contrast, HFL did not seem to contribute to AFB degradation. The obtained results contribute to our understanding of aflatoxin metabolism by different insect species. This information is crucial for assessing the safety of feeding fly larvae with feed substrates contaminated with AFB with the purpose of subsequent use as animal feed.
Topics: Animals; Aflatoxin B1; Larva; Biotransformation; Houseflies; Animal Feed; Diptera; Tandem Mass Spectrometry
PubMed: 38759532
DOI: 10.1016/j.ecoenv.2024.116449 -
Frontiers in Microbiology 2024This research aimed to address the issue of aflatoxin B (AFB) contamination, which posed severe health and economic consequences. This study involved exploring unique...
This research aimed to address the issue of aflatoxin B (AFB) contamination, which posed severe health and economic consequences. This study involved exploring unique species resources in the Qinghai-Tibet Plateau, screening strains capable of degrading AFB. UPLC-Q-Orbitrap HRMS and NMR were employed to examine the degradation process and identify the structure of the degradation products. Results showed that YUAD7, isolated from yak dung in the Qinghai-Tibet Plateau, removed 91.7% of AFB from TSB-AFB medium with an AFB concentration of 10 μg/mL (72 h, 37°C, pH 6.8) and over 85% of AFB from real food samples at 10 μg/g (72 h, 37°C), exhibiting strong AFB degradation activity. YUAD7's extracellular secretions played a major role in AFB degradation mediated and could still degrade AFB by 43.16% after boiling for 20 min. Moreover, YUAD7 demonstrated the capability to decompose AFB through processes such as hydrogenation, enzyme modification, and the elimination of the -CO group, resulting in the formation of smaller non-toxic molecules. Identified products include CHO, CHNO, CHO, CHNO, with a structure consisting of dimethoxyphenyl and enoic acid, dimethyl-amino and ethyl carbamate, polyunsaturated fatty acid, and aminomethyl. The results indicated that YUAD7 could be a potentially valuable strain for industrial-scale biodegradation of AFB and providing technical support and new perspectives for research on biodegradation products.
PubMed: 38751722
DOI: 10.3389/fmicb.2024.1367297 -
Advances in Neurotoxicology 2024The existing data demonstrate that probiotic supplementation affords protective effects against neurotoxicity of exogenous (e.g., metals, ethanol, propionic acid,...
The existing data demonstrate that probiotic supplementation affords protective effects against neurotoxicity of exogenous (e.g., metals, ethanol, propionic acid, aflatoxin B1, organic pollutants) and endogenous (e.g., LPS, glucose, Aβ, phospho-tau, α-synuclein) agents. Although the protective mechanisms of probiotic treatments differ between various neurotoxic agents, several key mechanisms at both the intestinal and brain levels seem inherent to all of them. Specifically, probiotic-induced improvement in gut microbiota diversity and taxonomic characteristics results in modulation of gut-derived metabolite production with increased secretion of SFCA. Moreover, modulation of gut microbiota results in inhibition of intestinal absorption of neurotoxic agents and their deposition in brain. Probiotics also maintain gut wall integrity and inhibit intestinal inflammation, thus reducing systemic levels of LPS. Centrally, probiotics ameliorate neurotoxin-induced neuroinflammation by decreasing LPS-induced TLR4/MyD88/NF-κB signaling and prevention of microglia activation. Neuroprotective mechanisms of probiotics also include inhibition of apoptosis and oxidative stress, at least partially by up-regulation of SIRT1 signaling. Moreover, probiotics reduce inhibitory effect of neurotoxic agents on BDNF expression, on neurogenesis, and on synaptic function. They can also reverse altered neurotransmitter metabolism and exert an antiamyloidogenic effect. The latter may be due to up-regulation of ADAM10 activity and down-regulation of presenilin 1 expression. Therefore, in view of the multiple mechanisms invoked for the neuroprotective effect of probiotics, as well as their high tolerance and safety, the use of probiotics should be considered as a therapeutic strategy for ameliorating adverse brain effects of various endogenous and exogenous agents.
PubMed: 38741946
DOI: 10.1016/bs.ant.2024.02.002 -
BMC Plant Biology May 2024Wheat is one of the essential crops for the human and animal nutrition, however, contamination with aflatoxigenic fungi, due to the improper storage conditions and high...
Wheat is one of the essential crops for the human and animal nutrition, however, contamination with aflatoxigenic fungi, due to the improper storage conditions and high humidity, was the main global threats. So, preventing the growth of aflatoxigenic fungi in stored wheat grains, by using different essential oils was the main objective of this work. Aspergillus flavus EFBL-MU12 PP087400, EFBL-MU23 PP087401 and EFBL-MU36 PP087403 isolates were the most potent aflatoxins producers inhabiting wheat grains. The effect of storage conditions of wheat grains "humidity, temperature, incubation period, and pH" on growth of A. flavus, was assessed by the response surface methodology using Plackett-Burman design and FCCD. The highest yield of aflatoxins EFBL-MU12 B and B by A. flavus grown on wheat grains were 145.3 and 7.6 μg/kg, respectively, at incubation temperature 35°C, 16% moisture contents, initial pH 5.0, and incubated for 14 days. The tested oils had a powerful antifungal activity for the growth and aflatoxins production by A. flavus in a concentration-dependent manner. Among these oils, cinnamon oil had the highest fungicidal activity for A. flavus at 0.125%, with about 85-90 % reduction to the aflatoxins B and B, conidial pigmentation and chitin contents on wheat grains. From the SEM analysis, cinnamon oils had the most deleterious effect on A. flavus with morphological aberrations to the conidial heads, vegetative mycelia, alteration in conidiophores identity, hyphae shrank, and winding. To emphasize the effect of the essential oils on the aflatoxins producing potency of A. flavus, the molecular expression of the aflatoxins biosynthetic genes was estimated by RT-qPCR. The molecular expression of nor-1, afLR, pKsA and afLJ genes was suppressed by 94-96%, due to cinnamon oil at 0.062% compared to the control. Conclusively, from the results, cinnamon oils followed by the peppermint oils displayed the most fungicidal activity for the growth and aflatoxins production by A. flavus grown on wheat grains.
Topics: Aspergillus flavus; Triticum; Oils, Volatile; Aflatoxins; Cinnamomum zeylanicum; Antifungal Agents; Fungicides, Industrial; Food Storage; Edible Grain
PubMed: 38741071
DOI: 10.1186/s12870-024-05065-w -
Se Pu = Chinese Journal of... Apr 2024Mycotoxins are toxic secondary metabolites produced by fungal species that can cause acute, subacute, and chronic toxicity in humans and animals. Thus, these toxins pose...
Mycotoxins are toxic secondary metabolites produced by fungal species that can cause acute, subacute, and chronic toxicity in humans and animals. Thus, these toxins pose a significant threat to health and safety. Owing to the lack of effective antimold measures in the agricultural industry, feed ingredients such as corn, peanuts, wheat, barley, millet, nuts, oily feed, forage, and their byproducts are prone to mold and mycotoxin contamination, which can affect animal production, product quality, and safety. Cyclopiazonic acid (CPA), which is mainly biosynthesized from mevalonate, tryptophan, and diacetate units, is a myotoxic secondary metabolite produced by and fungi. CPA is widely present as a copollutant with aflatoxins in various crops. Compared with some common mycotoxins such as aflatoxins, fumonisins, ochratoxins, zearalenones, and their metabolites, CPA has not been well investigated. In the United States, a survey showed that 51% of corn and 90% of peanut samples contained CPA, with a maximum level of 2.9 mg/kg. In Europe, CPA was found in -contaminated cheeses as high as 4.0 mg/kg. Some studies have shown that CPA can cause irreversible damage to organs such as the liver and spleen in mice. Therefore, the establishment of a rapid and efficient analytical method for CPA is of great significance for the risk assessment of CPA in feeds, the development of standard limits, and the protection of feed product quality and safety. The QuEChERS method, a sample pretreatment method that is fast, simple, cheap, effective, and safe, is widely used in the analysis of pesticide residues in food. In this study, a modified QuEChERS method combined with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine CPA levels in feeds. The chromatographic separation and MS detection of CPA as well as the key factors affecting the extraction efficiency of CPA, including the type of extraction solvent, type of inorganic salt, and type and dosage of adsorbent, were optimized in detail. During the optimization of the chromatographic-separation step, the acid and salt concentrations of the mobile phase affected the separation and detection of CPA. During the optimization of the QuEChERS method, the addition of a certain amount of acetic acid improved the extraction efficiency of CPA because of its acidic nature; in addition, GCB and PSA significantly adsorbed CPA from the feed extract. Under optimal conditions, the CPA in the feed sample (1.0 g) was extracted with 2 mL of water and 4 mL of acetonitrile (ACN) containing 0.5% acetic acid. After salting out with 0.4 g of NaCl and 1.6 g of MgSO, 1 mL of the ACN supernatant was purified by dispersive solid-phase extraction using 150 mg of MgSO and 50 mg of C and analyzed by UPLC-MS/MS. The sample was separated on a Waters HSS T3 column (100 mm×2.1 mm, 1.8 μm) using 2 mmol/L ammonium acetate aqueous solution with 0.5% formic acid and ACN as the mobile phases and then analyzed by positive electrospray ionization in multiple reaction monitoring mode. CPA exhibited good linearity in the range of 2-200 ng/mL, with a high correlation coefficient (=0.9995). The limits of detection and quantification of CPA, which were calculated as 3 and 10 times the signal-to-noise ratio, respectively, were 0.6 and 2.0 μg/kg, respectively. The average recoveries in feed samples spiked with 10, 100, and 500 μg/kg CPA ranged from 70.1% to 78.5%, with an intra-day precision of less than 5.8% and an inter-day precision of less than 7.2%, indicating the good accuracy and precision of the proposed method. Finally, the modified QuEChERS-UPLC-MS/MS method was applied to the analysis of CPA in 10 feed samples obtained from Wuhan market. The analysis results indicated that the developed method has good applicability for CPA analysis in feed samples. In summary, an improved QuEChERS method was applied to the extraction and purification of CPA from feeds for the first time; this method provides a suitable analytical method for the risk monitoring, assessment, and standard-limit setting of CPA in feed samples.
Topics: Tandem Mass Spectrometry; Animal Feed; Chromatography, High Pressure Liquid; Food Contamination; Indoles; Mycotoxins
PubMed: 38736387
DOI: 10.3724/SP.J.1123.2023.10030 -
Stress Biology May 2024Maize (Zea mays), a major food crop worldwide, is susceptible to infection by the saprophytic fungus Aspergillus flavus that can produce the carcinogenic metabolite...
MicroRNA (miRNA) profiling of maize genotypes with differential response to Aspergillus flavus implies zma-miR156-squamosa promoter binding protein (SBP) and zma-miR398/zma-miR394-F -box combinations involved in resistance mechanisms.
Maize (Zea mays), a major food crop worldwide, is susceptible to infection by the saprophytic fungus Aspergillus flavus that can produce the carcinogenic metabolite aflatoxin (AF) especially under climate change induced abiotic stressors that favor mold growth. Several studies have used "-omics" approaches to identify genetic elements with potential roles in AF resistance, but there is a lack of research identifying the involvement of small RNAs such as microRNAs (miRNAs) in maize-A. flavus interaction. In this study, we compared the miRNA profiles of three maize lines (resistant TZAR102, moderately resistant MI82, and susceptible Va35) at 8 h, 3 d, and 7 d after A. flavus infection to investigate possible regulatory antifungal role of miRNAs. A total of 316 miRNAs (275 known and 41 putative novel) belonging to 115 miRNA families were identified in response to the fungal infection across all three maize lines. Eighty-two unique miRNAs were significantly differentially expressed with 39 miRNAs exhibiting temporal differential regulation irrespective of the maize genotype, which targeted 544 genes (mRNAs) involved in diverse molecular functions. The two most notable biological processes involved in plant immunity, namely cellular responses to oxidative stress (GO:00345990) and reactive oxygen species (GO:0034614) were significantly enriched in the resistant line TZAR102. Coexpression network analysis identified 34 hubs of miRNA-mRNA pairs where nine hubs had a node in the module connected to their target gene with potentially important roles in resistance/susceptible response of maize to A. flavus. The miRNA hubs in resistance modules (TZAR102 and MI82) were mostly connected to transcription factors and protein kinases. Specifically, the module of miRNA zma-miR156b-nb - squamosa promoter binding protein (SBP), zma-miR398a-3p - SKIP5, and zma-miR394a-5p - F-box protein 6 combinations in the resistance-associated modules were considered important candidates for future functional studies.
PubMed: 38727957
DOI: 10.1007/s44154-024-00158-w -
Chinese Herbal Medicines Apr 2024A typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory.
OBJECTIVE
A typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory.
METHODS
A patient with herb-induced liver injury (HILI) and a history of taking XLGB Tablets before disease onset was engaged as the study subject, and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) and the integrated evidence chain (iEC) method recommended by the (HILI Guidelines).
RESULTS
Clinical history, biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral, alcoholic and autoimmune liver diseases on the diagnosis. Based on an investigation of the patient's medication history, she was suspected to have HILI caused by XLGB Tablets, as the patient was only taking an oral preparation of XLGB Tablets, and the influence of other drugs on the diagnosis was excluded. This patient with alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury. The relationship was considered "highly probable" (score of 9) using the updated RUCAM of 2016. Moreover, the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99, suggesting that the patient was consuming XLGB Tablets rather than another drug. LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug, and no chemical additions were found. Examination of the drug for pesticide residues, heavy metals, aflatoxins and other exogenous substances indicated compliance with the content limits of the .
CONCLUSION
In summary, the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC. Therefore, this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.
PubMed: 38706827
DOI: 10.1016/j.chmed.2023.10.005 -
Iranian Journal of Public Health Jan 2024Fungal metabolites known as aflatoxin M (AFM) are linked to contaminated milk and milk products. Consuming food contaminated with AFM poses major health risks and may...
BACKGROUND
Fungal metabolites known as aflatoxin M (AFM) are linked to contaminated milk and milk products. Consuming food contaminated with AFM poses major health risks and may even be fatal.
METHODS
The retrieved publications were categorized in this bibliometric study using the Web of Science (WoS) database Jan 1, 1970 to Nov 30, 2022 based on a variety of factors, including the time of publication of articles, citation totals, languages, research areas, countries, affiliations, funding agencies, journals, and keywords analysis to identify any hot and developing subjects. Additionally, VOSviewer software version 1.6.18 provided the bibliometric analysis of the global collaboration network and hot research themes.
RESULTS
Overall, 679 published documents were detected. Food Control was the top-line journal in publications on AFM research with 540 published articles, while the USA was the best productive country in AFM publications as well as the major country with the maximum co-authorship collaboration. This study ensures quantitative and qualitative analyses of the top 25 journals, most cited published articles, most relevant authors and title word occurrences in published documents on AFM publications. Over the past two decades, there has been an enormous rise for research conducted on global AFM.
CONCLUSION
The assessment of the historical state and development trend in AFM scientific research can serve as a roadmap for future research and eventually, serve as a foundation for bettering management practices for territorial decisions, healthcare, and dairy industries.
PubMed: 38694852
DOI: 10.18502/ijph.v53i1.14694 -
BMC Plant Biology May 2024Aspergillus flavus is an important agricultural and food safety threat due to its production of carcinogenic aflatoxins. It has high level of genetic diversity that is...
BACKGROUND
Aspergillus flavus is an important agricultural and food safety threat due to its production of carcinogenic aflatoxins. It has high level of genetic diversity that is adapted to various environments. Recently, we reported two reference genomes of A. flavus isolates, AF13 (MAT1-2 and highly aflatoxigenic isolate) and NRRL3357 (MAT1-1 and moderate aflatoxin producer). Where, an insertion of 310 kb in AF13 included an aflatoxin producing gene bZIP transcription factor, named atfC. Observations of significant genomic variants between these isolates of contrasting phenotypes prompted an investigation into variation among other agricultural isolates of A. flavus with the goal of discovering novel genes potentially associated with aflatoxin production regulation. Present study was designed with three main objectives: (1) collection of large number of A. flavus isolates from diverse sources including maize plants and field soils; (2) whole genome sequencing of collected isolates and development of a pangenome; and (3) pangenome-wide association study (Pan-GWAS) to identify novel secondary metabolite cluster genes.
RESULTS
Pangenome analysis of 346 A. flavus isolates identified a total of 17,855 unique orthologous gene clusters, with mere 41% (7,315) core genes and 59% (10,540) accessory genes indicating accumulation of high genomic diversity during domestication. 5,994 orthologous gene clusters in accessory genome not annotated in either the A. flavus AF13 or NRRL3357 reference genomes. Pan-genome wide association analysis of the genomic variations identified 391 significant associated pan-genes associated with aflatoxin production. Interestingly, most of the significantly associated pan-genes (94%; 369 associations) belonged to accessory genome indicating that genome expansion has resulted in the incorporation of new genes associated with aflatoxin and other secondary metabolites.
CONCLUSION
In summary, this study provides complete pangenome framework for the species of Aspergillus flavus along with associated genes for pathogen survival and aflatoxin production. The large accessory genome indicated large genome diversity in the species A. flavus, however AflaPan is a closed pangenome represents optimum diversity of species A. flavus. Most importantly, the newly identified aflatoxin producing gene clusters will be a new source for seeking aflatoxin mitigation strategies and needs new attention in research.
Topics: Aspergillus flavus; Aflatoxins; Multigene Family; Genome, Fungal; Secondary Metabolism; Zea mays; Genome-Wide Association Study; Genes, Fungal; Whole Genome Sequencing; Genetic Variation
PubMed: 38693487
DOI: 10.1186/s12870-024-04950-8