JOURNAL OF APPLIED TOXICOLOGY
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2020
·Vol. 41
·期 2
·265-275
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IF 2.997
Zhonghan He,Yanfeng Li,Zhenwei Lian,Jin Liu,Hongyi Xian,Ran Jiang,Zuqing Hu,Daokui Fang,Dalin Hu
Accumulating evidence reveals that exosome plays an important role in cell-to-cell communication in both physiological and pathological processes by transferring bioactive molecules. However, the role of exosomal secretion in the adaption of its source cells to the stimuli of environmental chemicals remains elusive. In this study, we revealed that the exposure of hydroquinone (HQ; the main bioactive metabolite of benzene) to human bronchial epithelial cells (16HBE) resulted in decreased ability of cell proliferation and migration, and simultaneously DNA damage and micronuclei formation. Interestingly, when exosomal secretion of HQ treated 16HBE cells was inhibited with the inhibitor GW4869, cellular proliferation and migration were further significantly reduced; concurrently, their DNA damage and micronuclei formation were both further significantly aggravated. Herein, we conclude that exosomal secretion of 16HBE cells may be an important self-protective function against the toxic effects induced by HQ.
研究领域:
细胞生物学
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毒理学
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分子生物学
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PubMed
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CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
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2020
·
IF 0.936
Wen-Nan FENG,Jin HE,Si-Ying LI,Dan YANG,Hong-Na LI,Guo-Cheng YANG,Qiang FU,Yu-Ping SHAN
In recent years, exosomes as the intercellular vehicles have received extensive attention for their fundamental roles in biosystem and as novel biomarkers for early detection and therapeutic applications. It has been demonstrated that anti-CD63 can effectively target exosomes from cancer cells. In this work, multifunctional nanoelectrode-nanopore nanopipettes (MNNPs) were prepared to detect exosomes secreted from human cervical cancer cells (HeLa cells) at the single-entity level using the nanopore- based resistive pulse sensing technique. Synthetic liposomes were also measured for comparison. By modifying the anti-CD63 on the carbon nanoelectrode surface near the nanopore, the detected current signals were very different from the signals from the non-modified MNNPs. The differences were induced by the specific interactions between anti-CD63 and the membrane protein CD63 at the surface of exosomes. No obvious differences were observed when liposomes were tested. Furthermore, by utilizing micromanipulation technology, the position of the nanopipette tip could be accurately located, which enabled monitoring the secretion of exosomes from individual cells in a real-time manner. In the control experiment, the probe-to-cell distance was optimized and the HeLa cells incubated with exosomes inhibitor (GW4869) were tested by MNNPs. These significantly reduced translocation signals proved that anti-CD63 modified MNNPs were competent for exosomes detection in complex cellular environments.
研究领域:
生物学
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纳米技术
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癌症研究
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生物医学工程
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高影响因子
TOXICOLOGY
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2024
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IF 4.8
Yiren Xiong,Guoqiang Guo,Hongyi Xian,Zuqing Hu,Di Ouyang,Jiayi He,Shanshan He,Renyi Liu,Zhenjie Gao,Meilin Tang,Ying Chen,Suqin Tan,Xiaoqi Zhu,Abudumijiti Abulimiti,Sujin Zheng,Hehai Huang,Dalin Hu
Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.
研究领域:
毒理学
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细胞生物学
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环境科学
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药理学
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2024
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IF 10.8
Qian Liu,Xiaoxun Lu,Ganzhong Liao,Fuhui Yan,Miaoliang Wu,Zhi Bai,Huanwen Tang,Xiaoshan Liu
Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant, the health risks of TPhP are a global concern. In this study, we found that prenatal TPhP exposure at human relevant concentration induced hyperlipidemia in male offspring, it increased serum levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol. Placental trophoblast-derived extracellular vesicles (T-EVs) could transport to the fetus through maternal-fetal circulation. TPhP significantly upregulated the protein level of peroxisome proliferator activated receptor γ (PPARγ) in T-EVs. Similar to TPhP, gestational exposure to T-EVs isolated from TPhP exposed mice placentae induced the same effects. While, gestational intervention with GW9662 (PPARγ inhibitor) or GW4869 (EVs secretion inhibitor) would alleviate the disturbed lipid metabolism induced by TPhP. Meanwhile, in vitro experiments verified that TPhP upregulated PPARγ in HTR8/SVneo cells derived EVs, and these EVs promoted adipogenesis in preadipocyte 3T3-L1 cells. Knock down of PPARγ in HTR8/SVneo could alleviate the adipogenensis effects of EVs derived from TPhP exposed HTR8/SVneo cells. These results demonstrate that TPhP exposure induces hyperlipidemia in male offspring by upregulating PPARγ in T-EVs. Our study provides new insights into the metabolic disruptive effects of TPhP, and emphasizes the mediating effects of placental T-EVs on gestational environmental stress in fetal development.
研究领域:
环境健康
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发育生物学
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代谢
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毒理学
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PubMed
高影响因子
PLoS Pathogens
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2024
·Vol. 20
·期 1
·e1011926
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IF 5.5
Zihao Wang,Ziming Jiang,Yu Zhang,Congwei Wang,Zhaoyang Liu,Zhankui Jia,Sudhanshu Bhushan,Jinjian Yang,Zhengguo Zhang
Uropathogenic Escherichia coli (UPEC) is the primary causative agent of urinary tract infections (UTIs) in humans. Moreover, as one of the most common bacterial pathogens, UPEC imposes a substantial burden on healthcare systems worldwide. Epithelial cells and macrophages are two major components of the innate immune system, which play critical roles in defending the bladder against UPEC invasion. Yet, the routes of communication between these cells during UTI pathogenesis are still not fully understood. In the present study, we investigated the role of membrane-bound nanovesicles (exosomes) in the communication between bladder epithelial cells and macrophages during UPEC infection, using an array of techniques such as flow cytometry, miRNA profiling, RNA sequencing, and western blotting. Moreover, our in vitro findings were validated in a mouse model of UPEC-induced cystitis. We found that UPEC infection induced the bladder epithelial MB49 cell line to secrete large numbers of exosomes (MB49-U-Exo), which were efficiently absorbed by macrophages both in vivo and in vitro. Assimilation of MB49-U-Exo induced macrophages to produce proinflammatory cytokines, including tumor necrosis factor (TNF)α. Exposure of macrophages to MB49-U-Exo reduced their phagocytic activity (by downregulating the expression of phagocytosis-related genes) and increased their rate of apoptosis. Mechanistically, we showed that MB49-U-Exo were enriched in miR-18a-5p, which induced TNFα expression in macrophages by targeting PTEN and activating the MAPK/JNK signaling pathway. Moreover, administration of the exosome secretion inhibitor GW4869 or a TNFα-neutralizing antibody alleviated UPEC-mediated tissue damage in mice with UPEC-induced cystitis by reducing the bacterial burden of the bladder and dampening the associated inflammatory response. Collectively, these findings suggest that MB49-U-Exo regulate macrophage function in a way that exacerbates UPEC-mediated tissue impairment. Thus, targeting exosomal -release or TNFα signaling during UPEC infection may represent promising non-antibiotic strategies for treating UTIs.
Urinary tract infections, which are typically caused by uropathogenic Escherichia coli (UPEC), affect over 150 million people each year, worldwide. Because the incidence of antibiotic resistance among UPEC strains is on the rise, urinary tract infections are becoming increasingly challenging to treat using this standard treatment method. Moreover, although the host immune response against UPEC has been intensively studied, the mechanism of communication between bladder epithelial cells and macrophages during UPEC infection remains largely unexplored. Here, we characterized the exosomes released from bladder epithelial cells following UPEC infection and evaluated their impact on macrophages. We demonstrated that bladder tissue destruction following excessive innate immune cell activation during UPEC infection may be driven by exosomes secreted from bladder epithelial cells. We further showed that pharmacologically inhibiting exosomal release from epithelial cells limited macrophage-associated inflammation, innate immune cell infiltration, and histopathological injuries in a mouse model of UPEC-induced cystitis. Collectively, our findings suggest that modulating exosome release represents a promising non-antibiotic therapy for UTIs.
研究领域:
微生物学
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免疫学
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分子生物学
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细胞生物学
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病理学
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PubMed
高影响因子
Food Bioscience
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2026
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IF 5.9
Hongye Li,Yun Bian,Yi Wu,Xueqing Hang,Mengqing Zhang,Luchuan Gao,Yifei Dong,Tanhang Mu,Wei Zhao
Gut microbial metabolism generates odor-active compounds that contribute to systemic malodor, particularly in the elderly. However, gut-targeted strategies to mitigate odor remain underexplored. This study evaluated the potential of in vitro gastrointestinal digested sugarcane polyphenols (SP) to suppress odor formation via microbial regulation using an in vitro fecal fermentation model. A combination of 16S rDNA sequencing, solid–phase microextraction coupled with gas chromatography–mass spectrometry (SPME–GC–MS), and ultra–performance liquid chromatography–quadrupole time–of–flight mass spectrometry (UPLC–Q–TOF–MS) was employed to investigate changes in microbial composition, odorant metabolites, and SP biotransformation. SP treatment significantly lowered key odorants, including indole, p-cresol, and dimethyl trisulfide, and selectively suppressed odor-associated taxa such as Enterobacteriaceae , Desulfovibrionaceae , and Veillonellaceae . Conversely, SP enriched beneficial bacteria, particularly Faecalibacterium and Bifidobacterium , suggesting a shift toward a health-associated gut microbial profile. UPLC–Q–TOF–MS identified 2''-O-acetylrutin and 2''-O-acetyl-3'-O-methylrutin as key SP-derived metabolites with putative antibacterial effects, potentially contributing to odor suppression. Exosome inhibition significantly attenuated both deodorization and microbiota remodeling, indicating that exosome-mediated microbial signaling may participate in the metabolic response to SP. These findings provide mechanistic insight into polyphenol-microbiota interactions and support SP as a promising functional dietary component for managing gut-derived malodor and promoting gastrointestinal health in the elderly. Further in vivo studies are needed to confirm these findings.
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IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
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2024
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IF 1.5
Chen Jiye,Chen Jiayao,Li Qinxia,Hu Minxia,Zhong Xingxing,Yu Liang,Zhang Xi,Huang Hongyu,Liu Jing,Huang Ziyi,Liu Xinyi,Xiong Wu
This study aimed to explore the potential of using mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) pre-treated with Astragaloside IV (ASIV) to alleviate inflammation in high glucose (HG)-damaged endothelial cells. MSC-Exos were isolated from untreated MSCs and ASIV-pre-treated MSCs, and their characteristics were assessed. The expression of miR-146a-5p in MSC-Exos was determined, and it was found that ASIV treatment enhanced its expression. In order to assess the impact of highly miR-146a-5p-expressing MSC-Exos on HG-injured endothelial cells, we established a model of HG-induced inflammation using human umbilical vein endothelial cells (HUVECs). The study measured cell viability, apoptosis, tube formation, and levels of inflammatory cytokines among the different treatment groups. It was found that transferring MSC-Exos with high miR-146a-5p expression to HG-damaged HUVECs increased cell viability and tube formation ability while reducing the number of apoptotic cells. Additionally, changes in inflammatory factors indicated a reduction in the inflammatory response. Further investigation demonstrated that miR-146a-5p inhibited the expression of TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB, which are involved in the inflammatory response. This resulted in the alleviation of inflammation in HG-damaged endothelial cells. In summary, our findings indicate that ASIV treatment stimulated the secretion of MSC-Exos that exhibited increased levels of miR-146a-5p. These exosomes, in turn, regulated the TRAF6/NF-κB pathway. As a result of this modulation, the inflammatory response in HG-damaged endothelial cells was alleviated. These findings offer a fresh approach to addressing vascular complications associated with diabetes, which could lead to novel treatment strategies in the field.
研究领域:
药理学
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细胞生物学
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分子生物学
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糖尿病研究
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高影响因子
Journal of Advanced Research
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2026
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IF 17.1
Weichen Dong,Wenxin Zhang,Li Huang,Lulu Xiao,Yuanfei Luo,Linying Yuan,Yike Jiang,Anyu Liao,Hongting Zhao,Zhihui Liu,Jia Wang,Ying Zhao,Yulong Cai,Mengna Peng,Dong Yang,Yi Xie,Kuanyu Li,Wusheng Zhu
Introduction Cardiolipins (CLs) are mitochondria-specific phospholipids critically involved in neurological disorders. However, their role in cerebral ischemia/reperfusion (I/R) injury remains largely underexplored. Objectives This study aimed to characterize CL alterations following cerebral I/R injury, identify potential mechanisms underlying CL loss, and investigate the pathophysiological effects of these changes. Methods Ischemic stroke was modeled by using middle cerebral occlusion/reperfusion (MCAO/R) in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro . CL alterations following cerebral I/R injury were evaluated through lipidomic analysis and fluorescent staining. The role of extracellular vesicles (EVs) in CL release was investigated. The effects of CL-targeting peptide SS-31 on CL release and homeostasis were assessed, and underlying mechanisms were explored by analyzing neuronal autophagy and ferroptosis. Plasma CL levels in stroke patients were also measured to elucidate clinical relevance. Results Significant CL depletion and acyl chain remodeling were observed in peri -infarct brain tissues. EV-mediated release was identified as one of the mechanisms of CL loss, and inhibiting EV release restored neuronal CL levels. SS-31 inhibits CL release, preserves CL content, and subsequently restores CL homeostasis. Restoring CL homeostasis attenuated cerebral I/R injury by suppressing neuronal ferroptosis. Mechanistically, SS-31 downregulated autophagy-associated genes, with ATG5 identified as the crucial target. Activating autophagy or overexpressing ATG5 reversed the protective effects of SS-31. Clinically, plasma CL levels in patients undergoing endovascular treatment correlated with 90-day functional outcomes. Conclusion Our findings establish CL preservation as a novel neuroprotective strategy, in which SS-31 mitigates I/R injury by restoring CL homeostasis and ameliorating ATG5-mediated autophagy-dependent neuronal ferroptosis, offering a novel therapeutic avenue for stroke.
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