FOOD AND CHEMICAL TOXICOLOGY
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2020
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IF 4.679
Di Wu,Shuangqiu Li,Peixuan Li,Aimin Jiang,Ziyi Liu,Yong Zhang,Jingjing Wang,Zhengtao Yang,Zhengkai Wei
Diacetoxyscirpenol (DAS) is one kind of type A trichothecene mycotoxin which produced by Fusarium species which contaminates agricultural crops and food . DAS attracts particular attention because of the strong toxicity. Heterophil extracellular traps (HETs) is a defense mechanism in the chicken innate immune. In this study, we firstly examine the effects and molecular mechanisms of DAS on HETs release, and then investigate the immune toxicity of DAS-induced HETs on chicken liver. HETs structures were observed by immunofluorescence staining and mechanisms were investigated by fluorescence microplate and Western blot . The results showed DAS triggered HETs formation which consists of chromatin decorated with citrullinated histone 3 (citH3) and elastase . Glycolysis was confirmed to be involved in this process and the inhibitors of NADPH oxidase , ERK 1/2 , p38 MAPK-signaling pathways and glycolysis significantly decreased HETs formation. Moreover, investigation in vivo showed DAS significantly increased HETs formation in serum and DNase I (a standard degradative agent of HETs) significantly decreased the ALT and AST levels and ameliorated DAS-caused inflammatory cell infiltration of liver. In conclusion, this study proves that DAS-induced HETs formation plays an immune toxicity role in chicken liver injury and these results provide a new therapeutic target for DAS-induced liver injury in chickens.
研究领域:
兽医学
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免疫学
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毒理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
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2023
·
IF 3.8
Yuxiao Qian,Yuqian Jiang,Hongrong Hong,Xinxin Gao,Wei Liu,Meiyi Chen,Qinqin Jin,Zha Jin,Xin Li,Xiaocen Wang,Jianhua Li,Quan Liu,Xichen Zhang,Nan Zhang,Zhengkai Wei
Pigeons are natural intermediate host of Neospora caninum ( N. caninum ). In comparison to ruminants, N. caninum causes milder clinical symptoms and less financial loss to pigeons. Natural infectious rates and high prevalence of N. caninum in pigeons, and death cases of N. caninum- infected pigeons under experimental conditions have been reported, but the detailed pathological characteristics and congenital immunological responses of pigeons-infected with N. caninum remain not well described. In this study, pigeons were infected intraperitoneally with 10 7 N. caninum tachyzoites . N. caninum in tissues was detected by qPCR. Pathological changes of tissues were examined by hematoxylin-eosin staining. Blood smears were prepared for counting eosinophils changes in blood. Heterophil extracellular traps (HETs) in vivo and in vitro were quantified by Pico Green. N. caninum- induced HETs structures were observed by immunofluorescence staining. The model of pigeons-infected with N. caninum was successfully established. Lung and duodenum were the main target organs of pigeons-infected with N. caninum . N. caninum caused hemorrhage, edema and inflammatory cell infiltration in liver, pulmonary congestion and hemorrhage, organizational destruction in lung, and shorter villi or even disappear in duodenum. N. caninum also increased the number of eosinophils in blood of pigeons. Moreover, N. caninum -induced HETs release in the congenital immunological system of pigeons were first demonstrated, and the HETs structures were consisted of DNA as the skeleton and modified with citH3 and elastase . N. caninum -induced HETs release was related with NADPH oxidase , TLR 2 and 4, ERK 1/2 and p38 MAPK signaling pathways , and glycolysis. In summary, it is the first report on the detailed pathological characteristics and congenital immunological responses of pigeons-infected with N. caninum , which may provide theoretical basis for the prevention and control of Neosporosis in pigeons.
研究领域:
兽医学
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免疫学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Yang Yong-Shi,Cao Meng-Da,Wang An,Liu Qing-Mei,Zhu Dan-Xuan,Zou Ying,Ma Ling-Ling,Luo Min,Shao Yang,Xu Dian-Dou,Wei Ji-Fu,Sun Jin-Lyu
Background: Allergic respiratory diseases have increased dramatically due to air pollution over the past few decades. However, studies are limited on the effects of inorganic components and particulate matter with different particle sizes in smog on allergic diseases, and the possible molecular mechanism of inducing allergies has not been thoroughly studied.Methods: Four common mineral elements with different particle sizes in smog particles were selected, including Al2O3, TiO2, Fe2O3, and SiO2. We studied the relationship and molecular mechanism of smog particle composition, particle size, and allergic reactions using mast cells, immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis (PCA) model, and an ovalbumin (OVA)-induced asthmatic mouse model in vitro and in vivo, combined with transmission electron microscopy, scanning transmission X-ray microscopy analysis, and transcriptome sequencing.Results: Only 20 nm SiO2 particles significantly increased β-hexosaminidase release, based on dinitrophenol (DNP)-human serum albumin (HSA) stimulation, from IgE-sensitized mast cells, while other particles did not. Meanwhile, the PCA model showed that Evan’s blue extravasation in mice was increased after treatment with nano-SiO2 particles. Nano-SiO2 particles exposure in the asthmatic mouse model caused an enhancement of allergic airway inflammation as manifested by OVA-specific serum IgE, airway hyperresponsiveness, lung inflammation injury, mucous cell metaplasia, cytokine expression, mast cell activation, and histamine secretion, which were significantly increased. Nano-SiO2 particles exposure did not affect the expression of FcϵRI or the ability of mast cells to bind IgE but synergistically activated mast cells by enhancing the mitogen-activated protein kinase (MAPK) signaling pathway, especially the phosphorylation levels of the extracellular signal-regulated kinase (ERK)1/2. The ERK inhibitors showed a significant inhibitory effect in reducing β-hexosaminidase release.Conclusion: Our results indicated that nano-SiO2 particles stimulation might synergistically activate IgE-sensitized mast cells by enhancing the MAPK signaling pathway and that nano-SiO2 particles exposure could exacerbate allergic inflammation. Our experimental results provide useful information for preventing and treating allergic diseases.
研究领域:
免疫学
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环境健康
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分子生物学
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过敏与哮喘
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BURNS
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2021
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IF 2.744
Biao Zhou,Te Ba,Lingfeng Wang,Yixuan Gao,Qiaoling He,Zengqiang Yan,Hongyu Wang,Guoliang Shen
Burns are a common traumatic injuries with considerable morbidity and mortality rates. Post-burn intestinal injuries are closely related to oxidative stress and inflammatory response. The aim of the current study was to investigate the combined effect of sodium butyrate (NaB) and probiotics (PROB) on severe burn-induced oxidative stress and inflammatory response and the underlying mechanism of action. Sprague-Dawley rats with severe burns were treated with NaB with or without PROB. Pathomorphology of skin and small intestine tissue was observed using hematoxylin and eosin staining and severe burn-induced apoptosis in small intestine tissue was examined via terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The release of factors related to inflammation was quantified using ELISA kits and qRT-PCR and levels of oxidative stress markers were evaluated using biochemical assays. Furthermore, mitochondrial morphological changes in small intestinal epithelial cells were observed using transmission electron microscopy . In addition, the underlying mechanism associated with the combined effect of NaB and PROB on severe burn-induced oxidative stress and inflammatory response was investigated using western blotting . The combination of NaB and PROB exerted protective effects against severe burn-induced intestinal barrier injury by reducing the levels of diamine oxidase and intestinal fatty acid binding protein . Combined NaB and PROB treatment inhibited severe burn-induced oxidative stress by increasing superoxide dismutase levels and decreasing those of malondialdehyde and myeloperoxidase levels. Severe burn-induced inflammation was suppressed by combined NaB and PROB administration, as demonstrated by the decreased mRNA expression of tumor necrosis factor-α, interleukin-6, interleukin-1β, and high mobility group box-1 in the small intestine. In addition, this study showed that combined NaB and PROB administration increased nuclear factor-erythroid 2-related factor 2 (Nrf2) protein expression and decreased the phosphorylation of nuclear factor (NF)-κB and extracellular signal-regulated kinase 1/2 (ERK 1/2). In conclusion, our findings indicate that combined NaB and PROB treatment may inhibit severe burn-induced inflammation and oxidative stress in the small intestine by regulating HMGB1/NF-κB and ERK1/2/Nrf2 signaling, thereby providing a new therapeutic strategy for intestinal injury induced by severe burn.
研究领域:
药理学
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免疫学
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病理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
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IF 4.8
Chengguang Zhao,Yali Zhang,Peng Zou,Jian Wang,Wenfei He,Dengjian Shi,Huameng Li,Guang Liang,Shulin Yang
A novel class of asymmetric mono-carbonyl analogs of curcumin (AMACs) were synthesized and screened for anti-inflammatory activity. These analogs are chemically stable as characterized by UV absorption spectra. In vitro, compounds 3f, 3m, 4b, and 4d markedly inhibited lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6 in a dose-dependent manner, with IC50 values in low micromolar range. In vivo, compound 3f demonstrated potent preventive and therapeutic effects on LPS-induced sepsis in mouse model. Compound 3f downregulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 MAPK and suppressed IκBα degradation, which suggests that the possible anti-inflammatory mechanism of compound 3f may be through downregulating nuclear factor kappa binding (NF-κB) and ERK pathways. Also, we solved the crystal structure of compound 3e to confirm the asymmetrical structure. The quantitative structure–activity relationship analysis reveals that the electron-withdrawing substituents on aromatic ring of lead structures could improve activity. These active AMACs represent a new class of anti-inflammatory agents with improved stability, bioavailability, and potency compared to curcumin. Our results suggest that 3f may be further developed as a potential agent for prevention and treatment of sepsis or other inflammation-related diseases.
研究领域:
药理学
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药物化学
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免疫学
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传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2023
·Vol. 22
·期 1
·1-14
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IF 4.5
Tan Lunbo,Ouyang Zijun,Chen Zhilong,Sun Fen,Guo Haichun,Wang Feng,Mulder Monique,Sun Yuan,Lu Xifeng,Zhang Jian V.,Danser A. H. Jan,Verdonk Koen,Fan Xiujun,Yang Qing
Background The adipokine chemerin regulates adipogenesis and the metabolic function of both adipocytes and liver. Chemerin is elevated in preeclamptic women, and overexpression of chemerin in placental trophoblasts induces preeclampsia-like symptoms in mice. Preeclampsia is known to be accompanied by dyslipidemia, albeit via unknown mechanisms. Here, we hypothesized that chemerin might be a contributor to dyslipidemia. Methods Serum lipid fractions as well as lipid-related genes and proteins were determined in pregnant mice with chemerin overexpression in placental trophoblasts and chemerin-overexpressing human trophoblasts. In addition, a phospholipidomics analysis was performed in chemerin-overexpressing trophoblasts. Results Overexpression of chemerin in trophoblasts increased the circulating and placental levels of cholesterol rather than triglycerides. It also increased the serum levels of lysophosphatidic acid, high-density lipoprotein cholesterol (HDL-C), and and low-density lipoprotein cholesterol (LDL-C), and induced placental lipid accumulation. Mechanistically, chemerin upregulated the levels of peroxisome proliferator-activated receptor g, fatty acid-binding protein 4, adiponectin, sterol regulatory element-binding protein 1 and 2, and the ratio of phosphorylated extracellular signal-regulated protein kinase (ERK)1/2 / total ERK1/2 in the placenta of mice and human trophoblasts. Furthermore, chemerin overexpression in human trophoblasts increased the production of lysophospholipids and phospholipids, particularly lysophosphatidylethanolamine. Conclusions Overexpression of placental chemerin production disrupts trophoblast lipid metabolism, thereby potentially contributing to dyslipidemia in preeclampsia.
研究领域:
妇产科学
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内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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