ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2019
·
IF 4.527
Yang Wu,Yan Li,Liangqing Zheng,Pengcheng Wang,Yan liu,Yongning Wu,ZhiYong Gong
Nε-(carboxymethyl)lysine (CML) is a potentially noxious compound that is causing widespread concern due to its use in various food products. In this study, we investigated CML neurotoxicity via an in vivo experiment with mice, and an in vitro experiment using a 3D microvascular network model (with human brain vascular endothelial cell and human astrocyte) that simulated the blood-brain barrier. We found that CML could induce cell survival status variations, and histopathological changes to the brain. In addition, CML increased levels of oxidative stress , prompted the protein expression of the receptor for advanced glycation end-products (RAGE). CML up-regulated both the gene expression of RAGE, the activating protein-1 (AP-1), the inflammatory cytokines Interleukin-6 (IL-6), vascular cell adhesion molecule1 (VCAM-1), monocyte chemotactic protein1 (MCP-1). We, therefore, postulated that CML has the potential to deleteriously affect the nervous system through oxidative stress and that activation of the p38 MAPK-AP-1 signaling pathway might be implicated in this pathological process.
研究领域:
神经科学
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毒理学
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细胞生物学
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食品科学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2026
·
IF 5.4
Chenyang Jiang,Xinshu Feng,Mingyu Qi,Shaojuan Wu,Qiuyu Wang,Yawen Zhou,Xiaoshan Zheng,Zhuogui Liang,Jianhua Tan,Yudong Zhang,Qingquan Guo,Haishan Zhao
Licorice ( Glycyrrhiza genus ) is a traditional medicinal herb that has also been widely used in the food and cosmetic industries, leading to widespread human exposure. Currently, many components have been identified as active ingredients in licorice; however, the toxic impurities and quality markers still require further investigation. Glabrol has been identified as a potentially toxic component in glabridin (an extract from licorice). In this study, we sought to evaluate the toxicity of glabrol in commercial licorice extracts and investigated the toxicological mechanism. The content of glabrol and the acute toxicity in ten commercial licorice extracts from different vendors were quantified using HPLC. The toxicity was further verified in zebrafish, cells in vitro and mammals in vivo mouse models . For the in vivo experiments, C57BL/6 mice received daily oral gavage of licorice extracts with (Sample C: 319.23 μg/g) o low (Sample B: 1.54 μg/g) glabrol content for 7 days. Locomotion was assessed via Open Field Test and Elevated Plus Maze, followed by blood and organ collection for pathological and biochemical analyses. To investigate the toxicological mechanism of glabrol, RNA - seq was performed on zebrafish embryos exposed to glabrol. Morphological and histopathological evaluations in zebrafish treated with the glabrol standard were carried out using phalloidin staining, transmission electron microscopy, and alizarin red staining. Our results indicated that glabrol was detected in all tested commercial licorice extracts, and its content showed a significant positive correlation with toxicity in cells and zebrafish. In mice, licorice extracts with higher glabrol levels led to low survival rates, hypoactivity, acute liver and kidney injury, and significantly elevated plasma inflammatory cytokines. Transcriptomic and mechanistic studies revealed that glabrol disrupted AP-1 signaling pathways and may impair myo-fiber organization, osteoclast differentiation, and inflammatory responses. This study establishes glabrol as a prevalent risk-associated impurity in licorice extracts and reveals that its toxicity is mediated via the AP-1 signaling pathway.
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Bixiao Liu,Fuying Zhu,Zhuqing Wang,Jiawen Chen,Xiaomiao Cui,Congzhong Yang,Yao Peng,Dengyuan Feng,Li Lu,Hui Wei,Xiaozhi Zhao
Renal ischemia-reperfusion (I/R) injury, a primary cause of acute kidney injury (AKI), is driven by a self-amplifying loop of oxidative burst and immune cell infiltration. In this work, the classical herb pair Astragalus membranaceus (AM) and Angelica sinensis (AS) is employed as a composite precursor to synthesize nitrogen-rich carbon-dot nanozymes (AM-AS@CDs) via a one-step hydrothermal method. AM‑AS@CDs exhibit superoxide dismutase (SOD)-mimetic activity superior to that of CDs derived from single herbs. In vitro, AM-AS@CDs effectively alleviate oxidative stress-induced cellular damage and significantly inhibit apoptosis. In vivo, AM-AS@CDs markedly attenuate I/R-induced AKI and reduce immune cell infiltration in renal tissues. Transcriptomic analyses reveal that AM-AS@CDs downregulate the expression and phosphorylation of Fosl1 and c-Jun. Consequently, the AP-1-chemokine signaling axis is disrupted, which reduces immune cell recruitment. Furthermore, AM-AS@CDs restore redox homeostasis by upregulating antioxidant enzymes such as SOD, glutathione peroxidase 4 (GPX4), and catalase (CAT). They also attenuate the excessive activation of the Nrf2/HO-1 pathway. Overall, this precursor-formulation strategy enables precise modulation of heteroatom doping and surface chemistry in CDs. AM-AS@CDs effectively interrupt the oxidative-inflammatory positive feedback loop through dual mechanisms. These findings provide both theoretical and material foundations for the development of natural product-based nanozymes for I/R-related diseases.
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DOI
PubMed
高影响因子
Aging-US
·
2024
·
IF 3.9
Yaming Yang,Zheng Yan,Qi Xie,Yong Wang,Zhiying Liu,Min Lei
Background: The purpose of this study is to observe LP45 ( Lactobacillus plantarum 45) to investigate the mechanism by which LP45 attenuates oxidative stress-induced damage and regulates the osteoblast-osteoclast balance. Materials and Methods: The oxidative stress level and osteoblast- and osteoclast-related proteins were detected by immunofluorescence staining, Western blotting, ROS fluorescent probe and ELISA. Osteoblast cell proliferation capacity was determined by the CCK-8 assay. X-ray observation and HE staining were used to detect the effect of LP45 on osteoporosis. Results: The expression level of SHP2 and Src was significantly increased, and the expression levels of NOX4, P22, P47, IL-1β, NLRP3, IRF3, RANK, β-catenin and INF-β were inhibited in LP45 group and LPS + LP45 group as compared to those in LPS group. Compared with that in LPS group, the concentration of SOD was increased and the concentration of MDA was decreased in LPS + LP45 group. The protein expressions of OPG, RANKL, RUNX3, RANK and β-catenin in LP45 group and LPS + LP45 group increased. The protein expressions of NF-κB, CREB and AP-1 in LP45 group and LPS + LP45 group decreased significantly. The results were also confirmed by immunofluorescence staining and ROS fluorescent probe. X-ray observation and HE staining showed that LP45 could inhibit the progression of osteoporosis. Conclusion: LP45 can exert its antioxidant effect by inhibiting the production of oxidative stress to activate the SHP2 signaling pathway, thus promoting osteoblast differentiation and repressing osteoclast formation to maintain bone homeostasis and improve bone metabolism.
研究领域:
微生物学
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骨骼生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 16
·8587
·
IF 13.3
Wei-Jia Yu,Wen-Xi Jiang,Shu-Jing Liu,Hui-Hua Li,Qiu-Yue Lin
Rationale: Infiltration of immune cells into the heart plays a crucial role in the transition from adaptive hypertrophy to heart failure (HF) following chronic pressure overload. However, the key factors in myeloid cells that regulate this process are still not well defined. Here, we studied the functional role of S100A8/A9 in myeloid cells during this transition. Methods: Cardiac hypertrophy and HF models were induced by transverse aortic constriction (TAC) for 1 to 4 weeks. The heterogeneity of CD45 + immune cells and the cellular sources of S100A8/A9 were analyzed using published single-cell RNA sequencing datasets. The effects of S100A8/A9 on TAC-induced hypertrophy and HF were verified in S100A9 knockout (KO) and bone marrow (BM)-chimeric mice and in an in vitro coculture system. Results: S100A8/A9 levels were significantly increased in HF patients and in TAC-induced HF model mice. Moreover, the TAC-induced transition from adaptive hypertrophy to HF was significantly attenuated in S100A9-KO mice and WT mice transplanted with S100A9-KO BM cells. Mechanistically, TAC-stimulated upregulation of S100A8/A9 in neutrophils induced an early inflammatory response and adaptive hypertrophy through activation of the p38 MAPK/JNK/AP-1 pathway, leading to increased production of IL-1β and chemokines (CCL2 and CCL6). These chemokines promoted the infiltration of CCR2 + macrophages to the damaged heart. Therefore, they exhibited upregulation of S100A8/A9, which led to exacerbation of inflammation, cardiac hypertrophy and fibrosis via activation of the NF-κB/NLRP3, AKT/Calcineurin A and TGF-β/Smad2 signaling pathways. Additionally, treating WT mice with the S100A9 inhibitor ABR-238901 prevented TAC-induced cardiac hypertrophy-related dysfunction. Conclusion: The present findings establish an S100A8/A9-related axis between myeloid cells and cardiac cells that drives the pressure overload-induced transition from hypertrophy to HF, suggesting that S100A8/A9 is a promising therapeutic target for this disease.
研究领域:
心脏病学
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免疫学
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分子生物学
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基因组学
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生物医学研究
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产品关联
DOI
PubMed
高影响因子
PHOTOCHEMISTRY AND PHOTOBIOLOGY
·
2023
·
IF 3.3
Xiaoying Mo,Xiaochun Chen,Xiaojiao Pan,Yantong Lu,Guangjuan Pan,Jielan Xie,Zhenzhen Pan,Li Li,Hui Tian,Yaohua Li
Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)-induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR-induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR-induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF-α, IL-1α, IL-1β, IL-6, and IL-8 by inhibiting the level of ROS, thus reducing inflammation-mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK–ERK/p38/JNK pathway. This downregulated the expression of activator protein-1 (AP-1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9 as well as reduced UVR-induced injury to the cells. In conclusion, HSE is a broad-spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products.
研究领域:
药理学
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皮肤病学
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植物科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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