Foods
·
2023
·Vol. 12
·期 13
·2555
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IF 5.2
Song Yu,Lianpeng Zou,Jiawei Zhao,Yiping Zhu
Human health is seriously threatened by mycotoxin contamination, yet health risk assessments are typically based on just one mycotoxin, potentially excluding the additive or competitive interactions between co-occurring mycotoxins. In this investigation, we evaluated the individual or combined toxicological effects of three fumonisin-family B mycotoxins: fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3), by using porcine intestinal epithelial cells (IPEC). IPEC cells were exposed to various concentrations (2.5–40 μM) for 48 h, and a cell counting kit (CCK8) was used to determine cell vitality. Firstly, we discovered that they might inhibit cell viability. Additionally, the cytotoxicity of FB1 was significantly greater than that of FB2 and FB3. The results also indicated that the combinations of FB1-FB2, FB2-FB3, and FB1-FB2-FB3 showed synergistically toxicological effects at the ID10-ID50 levels and antagonistic effects at the ID75-ID90 levels. In addition, the FB1-FB3 exposure was also synergistic at the ID10-ID25 level. We also found that myriocin and resveratrol alleviated the cytotoxicity induced by fumonisin in IPEC cells. In all, this study may contribute to the determination of legal limits, the optimization of risk assessment for fumonisins in food and feed, and the development of new methods to alleviate fumonisin toxicity.Keywords:fumonisins;gastrointestinal toxicity;combined toxicity;risk assessment;control strategy
研究领域:
毒理学
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食品安全
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兽医学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 5
·1-10
·
IF 4.026
Guo Chen,Zhu Xichun,Yuan Haoyang,Liu Haoyu,Zhang Yu,Yin Tian,He Haibing,Gou Jingxin,Tang Xing
In recent years, the oral administration of vinorelbine has gradually replaced intravenous administration in the treatment of several types of tumors. Even though the risk of phlebitis is avoided with oral administration, oral vinorelbine is still not a highly patient-compliant route due to the severe gastrointestinal toxicity. Vinorelbine-loaded liposomes with high encapsulation efficiency and suitable particle size were prepared using the ammonium sulfate gradient method. Chitosan-coated liposomes showed the slowest in vitro release compared to uncoated liposomes and vinorelbine solution. No damage was observed in the intestinal epithelial cells of mice orally administered with coated vinorelbine liposomes due to the low presence of the free drug in the gastrointestinal tract and the LD 50 was increased from 129.83 to 182.25 mg/kg compared to oral vinorelbine solution. In addition, the positive surface potential of chitosan-coating endowed liposomes with mucosal adhesive function, delaying the time to reach the peak plasma concentration of vinorelbine from 1 to 4 h after administration. And bioavailability was increased to 2.1-fold compared to vinorelbine solution. In short, a new strategy to address the severe gastrointestinal side effects of oral vinorelbine has been developed.
研究领域:
药剂学
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肿瘤学
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DOI
高影响因子
Frontiers in Nutrition
·
2025
·
IF 5.1
Min Du,Xinran Liu,Xu Ji,Yue Wang,Xiaodan Liu,Chunfang Zhao,Erhui Jin,Youfang Gu,Hongyu Wang,Feng Zhang
Introduction: Enterotoxic Escherichia coli (ETEC) is the main pathogen that causes diarrhea, especially in young children. This disease can lead to substantial morbidity and mortality and is a major global health concern. Managing ETEC infections is challenging owing to the increasing prevalence of antibiotic resistance. Berberine, categorized as a substance with similarities in “medicine and food,” has been used in China for hundreds of years to treat gastrointestinal disorders and bacteria-induced diarrhea. This study investigated the preventive effect of dietary berberine on the intestinal mucosal barrier induced by ETEC and the microbial community within the intestines of weaned piglets.Methods: Twenty-four piglets were randomly divided into four groups. Piglets were administered either a standard diet or a standard diet supplemented with berberine at concentrations of 0.05 and 0.1%. and orally administered ETEC or saline.Results: Dietary supplementation with berberine reduced diamine oxidase, d-lactate, and endotoxin levels in piglets infected with ETEC (P < 0.05). Berberine increased jejunal villus height, villus/crypt ratio, mucosal thickness (P < 0.05), and goblet cell numbers in the villi and crypts (P < 0.05). Furthermore, berberine increased the optical density of mucin 2 and the mucin 2, P-glycoprotein, and CYP3A4 mRNA expression levels (P < 0.05). Berberine increased the expressions of zonula occludins-1 (ZO-1), zonula occludins-2 (ZO-2), Claudin-1, Occludin, and E-cadherin in the ileum (P < 0.05). Moreover, berberine increased the expression of BCL2, reduced intestinal epithelial cell apoptosis (P < 0.05) and decreased the expression of BAX and BAK in the duodenum and jejunum, as well as that of CASP3 and CASP9 in the duodenum and ileum (P < 0.05). Berberine decreased the expression of IL-1β, IL-6, IL-8, TNF-α, and IFN-γ (P < 0.05) and elevated total volatile fatty acids, acetic acid, propionic acid, valeric acid, and isovaleric acid concentrations (P < 0.05). Notably, berberine enhanced the abundance of beneficial bacteria including Enterococcus, Holdemanella, Weissella, Pediococcus, Muribaculum, Colidextribacter, Agathobacter, Roseburia, Clostridium, Fusicatenibacter, and Bifidobacterium. Simultaneously, the relative abundance of harmful and pathogenic bacteria, such as Prevotella, Paraprevotella, Corynebacterium, Catenisphaera, Streptococcus, Enterobacter, and Collinsella, decreased (P < 0.05).Discussion: Berberine alleviated ETEC-induced intestinal mucosal barrier damage in weaned piglets models. This is associated with enhancement of the physical, chemical, and immune barrier functions of piglets by enhancing intestinal microbiota homeostasis.
研究领域:
医学
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微生物学
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兽医学
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营养学
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产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2021
·
IF 3
Dou-Dou XU,Xiao-Ying HOU,Ou WANG,Di WANG,Dan-Ting LI,Si-Yuan QIN,Bo LV,Xiao-Min DAI,Zun-Jian ZHANG,Jian-Bo WAN,Feng-Guo XU
Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF- α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E i, which taken the content and bioactivity into comprehensive consideration. And then, the most contributing constituents were selected out to form a key-component combination. At last, the bioefficacy of the key-component combination was validated in vitro and in vivo . As a result, a key-component combination (HB4) consisting of four compounds baicalin, baicalein, glycyrrhizic acid and wogonin was screened out. In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116. Furthermore, the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model. Meanwhile, HB4 could also reduce the CPT-11 induced GI toxicity.
研究领域:
药理学
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肿瘤学
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中医
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Xiuxiu Chen,Donghui Zhu,Renshan Ge,Zhijun Bao
Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors ( IL-1β, IL-6, TNF-α ), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins ( Claudin, Occludin, Muc2 ) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.
研究领域:
毒理学
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衰老研究
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胃肠病学
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微生物组
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代谢组学
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产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2025
·
IF 3.8
Cheng Shen,Guochen Li,Tianyi Han,Naila Ilyas,Meng He,Ziyan Huang,Xiao Zhang,Chongxin Xu,Chengyu Chen,Wei Chen,Xianjin Liu,Qing Zhu,Yuan Liu
BACKGROUND Bacillus thuringiensis (Bt) toxins are widely used in pest control owing to their effectiveness as bioinsecticides. However, the extensive use of these toxins has resulted in the development of resistance in various pest populations, including Plutella xylostella , which is a significant pest of cruciferous crops. This increasing resistance highlights the need for alternative insecticidal strategies that can complement or replace traditional methods. RESULTS A novel approach involves using insect cadherin receptors to screen for nanobodies with potential insecticidal activity that selectively target the toxin binding region of the Plutella xylostella cadherin toxin via phage display technology. Through three rounds of panning with a natural alpaca nanobody phage display library, we identified nanobody B1, which specifically binds to the CR9-CR11 region of Plutella xylostella cadherin. This nanobody significantly inhibited the binding of Cry1Ac toxin to cadherin, a key factor in insect susceptibility to the toxin. In bioassays, the application of soluble B1 protein (80 μg/cm 2 ) resulted in 25 ± 4.5% mortality in Plutella xylostella larvae. Histological examination of the midgut tissue revealed substantial damage to the epithelial layer, supporting the bioassay findings. Enzymatic hydrolysis assays demonstrated that, while B1 exhibited some stability, it showed limited resistance to enzymatic degradation in vitro . This could be a significant contributing factor to the low insecticidal activity of B1. CONCLUSION This study proposes a novel strategy for insecticide development based on the application of nanobodies to target cadherins within the midgut of Plutella xylostella . The identification of nanobody B1 presents a novel approach to circumvent resistance mechanisms in pest populations, overcoming resistance mechanisms in pest populations, and thus advancing sustainable pest management practices. Furthermore, these findings establish a foundation for designing alternative insecticidal proteins that could diminish the reliance on traditional formulations. © 2025 Society of Chemical Industry.
研究领域:
昆虫学
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生物技术
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害虫防治
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2025
·
IF 4.6
Yanli Lu,Yunge Liu,Xiaoyang Bai,Tao Jiang,Xiaowan Chen,Yanqiu Wang,Peipei Du,Yuhan Sun,Chuanxin Liu,Jiajia Duan
Podophyllotoxin (PPT), a lignan extracted from the roots and stems of Podophyllum species, exhibits significant enterotoxicity that limits its clinical application. However, its underlying mechanisms remain unclear. This study aimed to elucidate the mechanisms underlying PPT-induced enterotoxicity. Changes in body weight, fecal morphology, toxic phenotypes, and histopathological features were evaluated. 3D reconstruction, 16S rRNA sequencing, targeted short-chain fatty acids (SCFAs) analysis, and inflammatory cytokine assays were performed. The findings demonstrated that PPT induced pathological changes in rats, including weight loss, diarrhea, and colonic damage. PPT administration significantly reduced beneficial bacteria such as Lactobacillus , while increasing harmful bacteria such as Escherichia-Shigella . The predicted pathways of bacterial invasion of epithelial cells and lipopolysaccharide biosynthesis were significantly upregulated. Levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were also increased. Additionally, the expression of undecaprenyl-diphosphate synthase (UPPS) and SCFAs production was reduced. These findings indicate that PPT may alter gut microbial composition, increase Escherichia-Shigella invasion in the intestinal epithelial cells, promote lipopolysaccharide production, enhance the release of pro-inflammatory cytokines, including TNF-α and IL-6, and inhibit UPPS expression and SCFAs generation, collectively contributing to enterotoxicity. This study provides novel insights into the mechanisms behind PPT-induced enterotoxicity, which is essential for preventing and treating PPT toxicity.
研究领域:
药理学
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毒理学
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微生物学
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免疫学
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生物信息学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2024
·
IF 3.8
Lingling Wang,Zifeng Deng,Jieying Huang,Tingyuan Li,Jun Jiang,Wence Wang,Yu Sun,Yiqun Deng
ABSTRACT Zearalenone (ZEN), a mycotoxin produced by Fusarium species, is known for its reproductive toxicity as an estrogen analogue. However, there are limited knowledge about its hepatointestinal toxicity, as well as the role that gut microbiota and metabolites play in this process. In this study, a total of 24 thirty-week-old hens were fed to investigate the hepatointestinal toxicity subjected to long-term ZEN consumption at 2.0 mg/kg for 90 d. And we employed uncultured 16S rRNA sequencing for gut microbiota and untargeted metabolomics for fecal metabolites assessment. Notably, ZEN induced significant hepatic damage, as evidenced by hepatocyte necrosis, inflammatory cell infiltrate, increased liver lipopolysaccharide (LPS) and blood aspartate aminotransferase (AST) levels ( P < 0.05). The decreased villus height, disruption of simple columnar epithelial cells, and exposure of the mucosal intrinsic layer were observed in the intestine. The gut microbial community composition and metabolites differed between ZEN group and control group. ZEN group exhibited higher gut microbial diversity ( P < 0.05), lower Firmicutes/Bacteroidetes ratio and Lactobacillus abundance, and higher abundance in the genus such as Bacteroidetes, Parabacteroidetes and Desulfovibrio . Metabolomic analysis showed that ZEN treatment altered biosynthesis of siderophore group nonribosomal peptides and phenylpropanoids, metabolism of amino acid, digestion and absorption of vitamin and ABC transporters. Differential metabolites suggested that ZEN increase the risk of estrogen disorder, nucleic acid degradation, intestinal oxidative stress and inflammation. Neural network analysis showed that Ruminococcus was positively correlated with glyceric acid, and Prevotella was positively correlated with phenylacetylglycine. Both metabolites were positively correlated with blood AST level ( P < 0.05), suggesting that intestinal microbe Ruminococcus and Prevotella might exacerbate liver damage by producing these harmful metabolites. Overall, we conclude that ZEN has damaged hepatointestinal system and the altered gut microbiota with resultant metabolite changes contribute to the adverse hepatointestinal effects of ZEN on laying hens. This study underscores the need for monitoring and mitigating ZEN exposure in poultry diets, highlighting its broader implications for animal health and food safety.
研究领域:
兽医学
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毒理学
·
微生物学
·
动物营养学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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