JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2026
·
IF 4
Mengyu Hou,Qian Cheng,Zhenrong Xu,Deyi Kong,Zhixian Chen,Feiliang Zhong,Xuegang Luo
BACKGROUND Cyclophosphamide (CTX), a widely used alkylating chemotherapeutic agent, causes severe systemic immunosuppression and gut microbiota dysbiosis through non-specific cytotoxicity, increasing infection risk and impairing chemotherapy outcomes. Safe and effective adjuvant therapies for chemotherapy-related immune injury remain limited. This study evaluated the protective effect of compound AB probiotics ( Lactobacillus acidophilus LA15 combined with Bifidobacterium animalis subsp. lactis Bi66) against CTX-induced immunosuppression in mice and explored correlations associated with the gut-immune axis. RESULTS CTX challenge induced immune organ atrophy, cytokine imbalance, impaired innate and adaptive immunity, intestinal barrier disruption, reduced short-chain fatty acid (SCFA) synthesis and gut dysbiosis. AB probiotic intervention alleviated these injuries dose-dependently: it restored thymus and spleen indexes, rebalanced serum cytokines, improved core immune functions, and repaired ileal mucosal pathological damage. Furthermore, probiotic treatment was accompanied by elevated fecal SCFA concentrations, upregulated tight junction gene expression, recovered aryl hydrocarbon receptor (AhR)/ERK/STAT3 transcription, enriched beneficial bacterial genera, and suppressed opportunistic pathogens. CONCLUSION Compound AB probiotics alleviate CTX-induced immunosuppression in mice, and this effect correlates with restored gut microecology, enhanced SCFA metabolism, repaired intestinal barrier, and activated AhR signaling. These findings provide evidence for developing probiotic preparations as adjuvant interventions against chemotherapy-related immunosuppression. © 2026 Society of Chemical Industry.
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高影响因子
ENVIRONMENTAL POLLUTION
·
2017
·
IF 5.099
Zheng-Hai Du,Jun Xia,Xiao-Chen Sun,Xue-Nan Li,Cong Zhang,Hua-Shan Zhao,Shi-Yong Zhu,Jin-Long Li
Di-(2-ethylhexyl)-phthalate (DEHP) is causing serious health hazard in wildlife animal and human through environment and food chain, including the effect of brain development and impacted neurobehavioral outcomes. However, DEHP exposure caused cerebellar toxicity in bird remains unclear. To evaluate DEHP-exerted potential neurotoxicity in cerebellum, male quails were exposed with 0, 250, 500 and 750 mg/kg BW/day DEHP by gavage treatment for 45 days. Neurobehavioral abnormality and cerebellar histopathological alternation were observed in DEHP-induced quails. DEHP exposure increased the contents of total Cytochrome P450s (CYPs) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR) and aniline-4-hydeoxylase (AH) in quail cerebellum. The expression of nuclear xenobiotic receptors (NXRs) and the transcriptions of CYP enzyme isoforms were also influenced in cerebellum by DEHP exposure. These results suggested that DEHP exposure caused the toxic effects of quail cerebellum. DEHP exposure disrupted the cerebellar CYP enzyme system homeostasis via affecting the transcription of CYP enzyme isoforms. The cerebellar P450arom and CYP3A4 might be biomarkers in evaluating the neurotoxicity of DEHP in bird. Finally, this study provided new evidence that DEHP-induced toxic effect of quail cerebellum was associated with activating the NXRs responses and disrupting the CYP enzyme system homeostasis.
研究领域:
环境毒理学
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神经毒理学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
·
2024
·
IF 4.8
Wang Pengtao,Tao Wei,Li Qiujie,Ma Wanting,Jia Wei,Kang Yuting
Indole-3-aldehyde (I3A) is an intestinal microbial metabolite that regulates inflammation in various inflammatory diseases; however, its role in chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the anti-inflammatory effects and molecular mechanisms of I3A in COPD. We constructed in vivo models using cigarette smoke (CS)-stimulated mice and in vitro models using cigarette smoke extract (CSE)-stimulated MH-S cells. The results demonstrated that I3A significantly alleviated bronchial obstruction in mice with COPD and reduced the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, I3A decreased the levels of matrix metalloproteinases MMP2, MMP12, and inhibited the NF-κB p65/NLRP3 pathways. Further investigation revealed that I3A inhibited NF-κB activity by suppressing p65 phosphorylation and nuclear translocation in CSE-stimulated MH-S cells. The activation of the NF-κB and NLRP3 signaling pathways is mediated by histone deacetylase 5 (HDAC5) and HDAC6, both of which are inhibited by I3A. Subsequent experiments indicated that aryl hydrocarbon receptor (AHR) knockdown attenuated the inhibitory effect of I3A on pro-inflammatory cytokines and the HDACs/NF-κB/NLRP3 signaling pathways, highlighting the dependence of I3A's anti-inflammatory effects on the AHR receptor. Key messages
I3A effectively reduced lung inflammation in COPD mice by inhibiting the NF-κB pathway.
In CSE-stimulated MH-S cells, I3A suppressed p65 phosphorylation and nuclear translocation, thereby inhibiting NF-κB activity.
The activation of the NF-κB/NLRP3 pathways by HDAC5 and HDAC6 was diminished by I3A.
Through the activation of the AHR receptor, I3A suppressed the activities of HDAC5/6, leading to a decrease in inflammatory factor levels.
Graphical abstract
研究领域:
呼吸病学
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免疫学
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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
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Xiaoying Lin,Hongxin Xie,Yanfei Zhang,Xuejia Wang,Yinghui Ma,Huifeng Zhang,Chengyi Hao,Shangqiang Mu,Qingxuan Liu,Qiuju Li,Nianqiu Shi,Liwei Cui,Rui Zhao,Bai Li,Yu-Feng Li
Neurodegenerative diseases bring heavy burden to our society. Methylmercury (MeHg) is a potent neurotoxin and causes neurodegenerative diseases like Minamata Disease. Therefore, finding ways to combat MeHg-induced neurodegeneration may shed light on the treatment of neurodegenerative diseases. This study investigated the efficacy of bismuth selenide nanoparticles (Bi 2 Se 3 NPs, nBS) in treating MeHg-induced neurodegeneration. MeHg-poisoned rats were orally given nBS (4 mg/kg) every other day for 21 days and then sacrificed. It was found that nBS improved neurobehavioral performance, alleviated hippocampus damage and intestinal barrier damage, reduced Hg accumulation, and promoted MeHg demethylation in MeHg-poisoned rats. In addition, nBS up-regulated the abundance of gut microbes such as Faecalibacterium, Bifidobacterium and Akkermansiaceae, and increased the levels of butyric acid in feces while reduced the concentration of isobutyric acid in the brains. At the same time, nBS reduced the secretion of inflammatory factors IL-6 and TNF-α in the brains, guts and serum, and regulated AHR/IDO expression in the guts and brains. In all, nBS treatment improved the health status of MeHg-poisoned rats through enhancing Hg excretion and MeHg demethylation, reshaping gut microbiota, and reducing neuroinflammation. These findings suggested that nBS supplementation is a promising approach to treat MeHg-induced neurodegeneration, which may shed lights on the treatment of neurodegenerative diseases.
研究领域:
神经科学
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毒理学
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纳米医学
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环境健康
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肠脑轴
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DOI
PubMed
高影响因子
Journal of Hazardous Materials Advances
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2026
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IF 9.1
Pengyun Ling,Linli Cai,Gang Li,Benhua Jin,Weibin Zhai,Qingqiang Xu,Yuanlan Huang
High-altitude hypoxia induces multisystem adaptive changes, yet its impact on the gut-kidney axis remains poorly understood. In this exploratory pilot study, we investigated the potential role of indole-3-acetic acid (IAA), a uremic toxin derived from tryptophan metabolism, in high-altitude-associated kidney injury. Untargeted metabolomics revealed an association between elevated IAA levels and renal function parameters: serum, urinary, and fecal IAA levels were significantly higher in high-altitude residents (> 4000 m) compared with lowland controls (< 500 m). In the pooled analysis, serum IAA was inversely correlated with eGFR ( r = -0.687, P < 0.001) and showed preliminary predictive potential for subclinical kidney injury (AUC = 0.942; 95 % CI: 0.839–1.000, though the wide confidence interval and small sample size warrant cautious interpretation). In vitro, IAA activated the aryl hydrocarbon receptor (AhR) signaling pathway in HK-2 cells in a concentration-dependent manner, inducing oxidative stress, fibrosis, and apoptosis. These effects were reversed by the AhR antagonist CH-223,191 and recapitulated by the AhR agonist FICZ. CoCl₂-induced hypoxia synergistically augmented IAA-induced AhR pathway activation and cytotoxicity. Public transcriptomic analyses further showed AHR and CYP1B1 upregulation in chronic kidney disease (CKD) and diabetic kidney disease (DKD) kidney tissues, with significant positive correlations between HIF1A and AHR expression. Collectively, these preliminary findings suggest a potential association linking high-altitude hypoxia, elevated IAA, AhR activation, and kidney injury, but due to the limited sample size, they should be interpreted as hypothesis-generating and require validation in larger independent cohorts.
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2024
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IF 8
Yingying Liang,Hailin Liu,Lin Wang,Jing Zhao,Shunyi Li,Li Yi,Sijing Jiang,Zhenghui Lu,Guimin Zhang
Dioxin-like compounds (DLCs) are environmental xenobiotics that can activate the aryl hydrocarbon receptors (AhR), thereby imposing a significant threat to human health through biomagnifications processes. In this study, a dioxin-activated nano-luminescent Saccharomyces cerevisiae bioreporter, called DnaSc, was developed for simple and rapid detection of DLCs and AhR agonists. The bioreporter used nano-luciferase (NLuc) as a signal generator to emit bioluminescent signals in response to DLCs without cell lysis. Through optimizing AhR nuclear translocator (ARNT) expression and engineering the AhR, the yeast-based bioassay exhibited a detection limit of 10 fM for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within 6 h, making it the most sensitive whole-cell biosensor reported to date. Furthermore, the detection capacity of the dioxin-activated nano-luminescent S. cerevisiae bioreporter (DnaSc) bioassay for DLCs and AhR agonists was characterized. In summary, the yeast-based bioreporter developed in this study provided a simple, sensitive, and cost-effective method for DLCs detection.
研究领域:
环境科学
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毒理学
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生物技术
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分子生物学
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高影响因子
Food & Function
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2023
·Vol. 14
·期 10
·4905-4920
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IF 6.1
Pengfei Fan,Huali Meng,Wenhao Hao,Yan Zheng,Hui Li,Zhiyue Zhang,Lei Du,Xin Guo,Dongliang Wang,Yunyan Wang,Hao Wu
Atherosclerosis (AS)-induced cardiovascular disease is a leading cause of death worldwide. To date, there is still a lack of effective approaches for AS intervention. Cardamonin (CAD) is a bioactive food component, but its effect on AS is unknown. In this work, CAD was investigated for its effect on AS using low-density lipoprotein receptor knockout mice and tumor necrosis factor-alpha (TNF-α)-stimulated endothelial cells (ECs). After a 12-week intervention, CAD was found to significantly prevent AS formation in the aortic root and aortic tree, reduce the necrotic core area, and inhibit aortic inflammation and oxidative stress. Moreover, CAD quenched TNF-α-provoked inflammation and oxidative stress in ECs. RNA-sequencing identified nuclear factor erythroid-2 related factor 2 (NFE2L2, NRF2)/heme oxidase 1 (HO1) signaling to be drastically activated by CAD. CAD is a known activator of the aryl hydrocarbon receptor (AHR) which is a transcription factor of the NFE2L2 gene. Surprisingly, AHR was not required for CAD's action on the activation of NRF2/HO1 signaling since AHR gene silencing did not reverse this effect. Furthermore, a molecular docking assay showed a strong binding potential of CAD to the Kelch domain of the Kelch-like ECH-associated protein 1 (KEAP1) which sequesters NRF2 in the cytoplasm. Both CAD and the Kelch domain inhibitor Ki696 promoted NRF2 nuclear translocation, whereas the combination of CAD and Ki696 did not yield a greater effect compared with either CAD or Ki696, confirming the interaction of CAD with the Kelch domain. This work provides an experimental basis for CAD as a novel and effective bioactive food component in future AS interventions.
研究领域:
心血管疾病
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药理学
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分子生物学
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细胞生物学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2022
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IF 5.714
Min Luo,Dan Luo,Jie Liu,Huailing Wang,Xiaoyu Liu,Min Yang,Fangfang Tian,Suofu Qin,Yuying Li
Probiotics are living bacteria that provide health benefits to the host when consumed in sufficient quantities. However, the protective effect of the bioactive peptides isolated from the probiotics against benzo(α)pyrene (BaP) induced gastrointestinal injury has never been investigated. The current work used a bio-assay guided technique to identify-four new cyclic peptides in BaP-induced Caco-2 cell culture and mouse colitis model. Lactobacillus rhamnosus cycle (Thr-His-Ala-Trp) peptide-1 (LRCP-1) effectively inhibited BaP-induced epithelial cytokine over-release and intracellular ROS over-production. Simultaneously, LRCP-1 attenuated BaP-induced NAD (P)H: oxidases (NOXs), Matrix metalloproteinases (MMPs) over-expression, respectively. Furthermore, increased NAD (P)H: quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1)/nuclear factor E2-related factor 2 (Nrf2) expression and aryl hydrocarbon receptor (AhR) pathway activation induced by the BaP-exposure were also inhibited after the LRCP-1 treatment. Notably, LRCP-1 is a promising agent protecting gastrointestinal epithelial cells from BaP-induced inflammatory and oxidative damages.
研究领域:
胃肠病学
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免疫学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2022
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IF 7.129
Chao Zhao,Hu Zhang,Jingjing Zhou,Qiwei Liu,Qiang Lu,Ying Zhang,Xiaojin Yu,Shizhi Wang,Ran Liu,Yuepu Pu,Lihong Yin
Esophageal squamous cell carcinoma (ESCC) is an environment-relevant malignancy with a high mortality. Nitrosamines, a class of nitrogen-containing environmental carcinogens, are widely suggested as a risk factor for ESCC. However, how nitrosamines affect metabolic regulation to promote ESCC tumorigenesis is largely unknown. In this study, the transition trajectory of serum metabolism in the course of ESCC induced by N-nitrosomethylbenzylamine (NMBA) in rats was depicted by an untargeted metabolomic analysis, and the potential molecular mechanisms were revealed. The results showed that the metabolic alteration in rats was slight at the basal cell hyperplasia (BCH) stage, while it became apparent when the esophageal lesion developed into dysplasia (DYS) or more serious conditions. Moreover, serum metabolism of severe dysplasia (S-DYS) showed more similar characteristics to that of carcinoma in situ (CIS) and invasive cancer (IC). Aberrant nicotinate (NA) and nicotinamide (NAM) metabolism, tryptophan (TRP) metabolism, and sphingolipid metabolism could be the key players favoring the malignant transformation of esophageal epithelium induced by NMBA. More particularly, NA and NAM metabolism in the precancerous stages and TRP metabolism in the cancerous stages were demonstrated to replenish NAD + in different patterns. Furthermore, both the IDO1-KYN-AHR axis mediated by TRP metabolism and the SPHK1-S1P-S1PR1 axis by sphingolipid metabolism provided an impetus to create the pro-inflammatory yet immune-suppressive microenvironment to facilitate the esophageal tumorigenesis and progression. Together, these suggested that NMBA exerted its carcinogenicity via more than one pathway, which may act together to produce combination effects. Targeting these pathways may open up the possibility to attenuate NMBA-induced esophageal carcinogenesis. However, the interconnection between different metabolic pathways needs to be specified further. And the integrative and multi-level systematic research will be conducive to fully understanding the mechanisms of NMBA-induced ESCC.
研究领域:
肿瘤学
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代谢组学
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毒理学
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分子生物学
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
·
IF 6.8
Juanjuan Duan,Hong Li,Yu Wang,Yongchao Ji,Chao Chen,Chengqiang Feng,Wensheng Zhang
Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant which mainly exposed though diet. High-fat diet (HFD) can induce atherosclerosis, as can BaP. Unhealthy dietary habits lead to high intake of both BaP and lipids. However, the combined effect of BaP and HFD on atherosclerosis and lipid accumulation in the arterial wall, the initial stage of atherosclerosis, is unclear. In this study, C57BL/6 J mice were subchronically exposed to BaP and a HFD, and the mechanism of lipid accumulation was investigated in EA.hy926 and HEK293 cells. Results showed that BaP and HFD increased blood lipids and damaged aortic wall synergistically. Meanwhile, LDL enhanced the toxicity of BaP, and BaP promoted the production of reactive oxygen species and malonaldehyde in EA.hy926 cells, which aggravated LDL-induced cell injury. Moreover, BaP and HFD/LDL induced LDL accumulation in the aortic wall of C57BL/6 J mice/EA.hy926, and the mechanism was by activating AHR/ARNT heterodimer to combine with the scavenger receptor BⅠ (SR-BⅠ) and activin receptor-like kinase 1 (ALK1) promoter regions to transcriptional upregulate its expression, which enhanced the uptake of LDL, and promoting the production of AGEs to inhibit reverse cholesterol transport by SR-BI. BaP and lipid synergistically promoted aortic and endothelial damage, and the health risk of their combined intake should be paid attention to.
研究领域:
毒理学
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心血管疾病
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环境健康
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细胞生物学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Xiudan Wang,Rui Tian,Chenghong Liang,Yifan Jia,Lingyun Zhao,Qinyuan Xie,Fenglian Huang,Huijuan Yuan
Insulin resistance and pancreatic β -cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H 2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet β -cell and enhanced pancreatic β -cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.
研究领域:
纳米技术
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糖尿病研究
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胃肠病学
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药理学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2022
·
IF 6.064
Xu Jue,Lan Yue,Wang Xinqi,Shang Ke,Liu Xu,Wang Jiao,Li Jing,Yue Bisong,Shao Meiying,Fan Zhenxin
Aging is a complex multifactorial process that greatly affects animal health. Multi-omics analysis is widely applied in evolutionary biology and biomedical research. However, whether multi-omics can provide sufficient information to reveal comprehensive changes in aged non-human primates remains unclear. Here, we explored changes in host–microbe interactions with aging in Chinese rhesus macaques (Macaca mulatta lasiota, CRs) using multi-omics analysis. Results showed marked changes in the oral and gut microbiomes between young and aged CRs, including significantly reduced probiotic abundance and increased pathogenic bacterial abundance in aged CRs. Notably, the abundance of Lactobacillus, which can metabolize tryptophan to produce aryl hydrocarbon receptor (AhR) ligands, was decreased in aged CRs. Consistently, metabolomics detected a decrease in the plasma levels of AhR ligands. In addition, free fatty acid, acyl carnitine, heparin, 2-(4-hydroxyphenyl) propionic acid, and docosahexaenoic acid ethyl ester levels were increased in aged CRs, which may contribute to abnormal fatty acid metabolism and cardiovascular disease. Transcriptome analysis identified changes in the expression of genes associated with tryptophan metabolism and inflammation. In conclusion, many potential links among different omics were found, suggesting that aged CRs face multiple metabolic problems, immunological disorders, and oral and gut diseases. We determined that tryptophan metabolism is critical for the physiological health of aged CRs. Our findings demonstrate the value of multi-omics analyses in revealing host–microbe interactions in non-human primates and suggest that similar approaches could be applied in evolutionary and ecological research of other species.
研究领域:
衰老生物学
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微生物组研究
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代谢组学
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转录组学
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免疫学
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非人灵长类动物
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）