摘要：
Multiple pesticides are often used in combination for plant protection and public health. Therefore, it is important to analyze the physiological changes induced by multiple pesticides exposure. The objective of this study was to investigate the combined toxicity of the widely-used organophosphorus and pyrethroid pesticides diazinon, dimethoate, and cypermethrin. Male Wistar rats were administrated by gavage once daily with the three pesticides individual or in combination for consecutive 28 days. The metabolic components of serum and urine samples were detected by using 1H nuclear magnetic resonance (NMR)-based metabolomics method. Histopathological examination of liver and kidneys and serum biochemical determination were also carried out. The results showed that after the 28-day subacute exposure, serum glutamic transaminase and albumin were significantly increased and blood urea nitrogen was significantly decreased in the rats exposed to the mixture of the pesticides compared with the control rats, suggesting that the co-exposure impaired liver and kidney function. Metabolomics analysis indicated that the indicators 14 metabolites were statistically significant altered in the rats after the exposure of the pesticides. The increase in 3-hydroxybutyric acid in urine or decrease of lactate and N-acetyl-L-cysteine in serum could be a potentially sensitive biomarker of the subchronic combined effects of the three insecticides. The reduction level of 2-oxoglutarate and creatinine in urine may be indicative of dysfunction of liver and kidneys. In summary, the exposure of rats to pesticides diazinon, dimethoate, and cypermethrin could cause disorder of lipid and amino acid metabolism, induction of oxidative stress, and dysfunction of liver and kidneys, which contributes to the understanding of combined toxic effects of the pesticides revealed by using the metabolomics analysis of the urine and serum profiles.
摘要：
Given that intricate toxicological profiles exist among different antibiotics and pose serious threats to the environment and human health, synchronous analysis of multiple residues becomes crucial. Sensor arrays show potential to achieve the above purpose, but it is challenging to develop easy-to-use and high-sensitivity tools because the state-of-the-art arrays often require more than one recognition unit and are monosignal dependent. Here we exquisitely designed a fluorescent nanoprobe (2-aminoterephthalic acid-anchored CdTe quantum dots with Eu3+ coordination, CdTe-ATPA-Eu3+) featuring triple emissions at the same excitation as the only element to fabricate a luminescent sensor array with ratiometric calculations for identifying multiple antibiotics. By taking tetracycline, chlortetracycline, doxycycline, oxytetracycline, penicillin G, and sulfamethoxazole as models, the six species exhibited distinguishable motivation or/and quenching impacts on the three emissions of CdTe-ATPA-Eu3+, which were employed as indicators to perform the ratiometric logical operation and further combined with pattern recognition analysis for multitarget determination. Evidently, such a design exhibits two advances: (1) with the triple-emission probe as the sole receptor requiring neither internal nor external adjustments, the fabricated array acts as an extremely facile tool for multianalyte detection; (2) the ratiometric calculations offer excellent sensitivity and reliability for high-performance determination. Consequently, accurate identification and quantification of individual antibiotics and their combinations at various levels were verified in both laboratory and practical matrices. Our work provides a new tool for simultaneously detecting multiple antibiotics, and it will inspire the development of advanced sensor arrays for multitarget analysis.
作者机构：
[Wang, Jingyu; Bai, Qinqin; Liang, H; Zheng, Yi; Zhao, Fengxia; Liang, Hao; Yan, Hangli; Wu, Linghao; Niu, Xiangheng] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, Hengyang 421001, Peoples R China.;[Hu, Hongmei] Hengyang Ctr Dis Control & Prevent, Hengyang 421001, Peoples R China.
通讯机构：
[Liang, H ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, Hengyang 421001, Peoples R China.
摘要：
The detection of foodborne pathogens is crucial for food hygiene regulation and disease diagnosis. Colorimetry has become one of the main analytical methods in studying foodborne pathogens due to its advantages of visualization, low cost, simple operation, and no complex instrument. However, the low sensitivity limits its applications in early identification and on-site detection for trace analytes. In order to overcome such a limitation, herein we propose a joint strategy featuring dual signal amplification based on the hybridization chain reaction (HCR) and DNA-enhanced peroxidase-like activity of gold nanoparticles (AuNPs) for the sensitive visual detection of Escherichia coli. Target bacteria bound specifically to the aptamer domain in the capture hairpin probe, exposing the trigger domain for HCR and forming the extended double-stranded DNA (dsDNA) structures. The peroxidase-like catalytic capacity of AuNPs can be enhanced significantly by dsDNAs with the sticky ends of dsDNAs being adsorbed on AuNPs and the rigidity of dsDNAs causing the spatial regulation of AuNP concentration. The intensity of the enhancement was linearly related to the number of target bacteria. With the above strategy, the detection limit of our colorimetric method for Escherichia coli was down to 28 CFU mL(-1) within a short analytical time (50 min). This study provides a new perspective for the sensitive and visual detection of early bacterial contamination in foods.
摘要：
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) persistently kills nearly 1.5 million lives per year in the world, whereas the only licensed TB vaccine BCG exhibits unsatisfactory efficacy in adults. Taking BCG as a vehicle to express Mtb antigens is a promising way to enhance its efficacy against Mtb infection. In this study, the immune efficacy of recombination BCG (rBCG-ECD003) expressing specific antigens ESAT-6, CFP-10, and nDnaK was evaluated at different time points after immunizing BALB/c mice. The results revealed that rBCG-ECD003 induced multiple Th1 cytokine secretion including IFN-γ, TNF-α, IL-2, and IL-12 when compared to the parental BCG. Under the action of PPD or ECD003, rBCG-ECD003 immunization resulted in a significant increase in the proportion of IL-2(+) and IFN-γ(+)IL-2(+) CD4(+)T cells. Importantly, rBCG-ECD003 induced a stronger long-term humoral immune response without compromising the safety of the parental BCG vaccine. By means of the protective efficacy assay in vitro, rBCG-ECD003 showed a greater capacity to inhibit Mtb growth in the long term. Collectively, these features of rBCG-ECD003 indicate long-term protection and the promising effect of controlling Mtb infection.
摘要：
An in vivo model is necessary for toxicology. This review analyzed the uses of zebrafish (Danio rerio) in toxicology based on bibliometrics. Totally 56,816 publications about zebrafish from 2002 to 2023 were found in Web of Science Core Collection, with Toxicology as the top 6 among all disciplines. Accordingly, the bibliometric map reveals that "toxicity" has become a hot keyword. It further reveals that the most common exposure types include acute, chronic, and combined exposure. The toxicological effects include behavioral, intestinal, cardiovascular, hepatic, endocrine toxicity, neurotoxicity, immunotoxicity, genotoxicity, and reproductive and transgenerational toxicity. The mechanisms include oxidative stress, inflammation, autophagy, and dysbiosis of gut microbiota. The toxicants commonly evaluated by using zebrafish model include nanomaterials, arsenic, metals, bisphenol, and dioxin. Overall, zebrafish provide a unique and well-accepted model to investigate the toxicological effects and mechanisms. We also discussed the possible ways to address some of the limitations of zebrafish model, such as the combination of human organoids to avoid species differences.
摘要：
Pyroptosis is a gasdermins-mediated programmed cell death that plays an essential role in immune regulation, and its role in autoimmune disease and cancer has been studied extensively. Increasing evidence shows that various microbial infections can lead to pyroptosis, associated with the occurrence and development of microbial infectious diseases. This study reviews the recent advances in pyroptosis in microbial infection, including bacterial, viral, and fungal infections. We also explore potential therapeutic strategies for treating microbial infection-related diseases by targeting pyroptosis.
摘要：
Four new ansamycin derivatives, named 1,19-epithio-geldanamycin A (1), 17-demethoxylherbimycin H (2), herbimycin M (3), and seco-geldanamycin B (4), together with eight known ansamycin analogues (5-12) were isolated from the solid fermentation of marine-derived actinomycete Streptomyces sp. ZYX-F-97. The structures of new compounds were elucidated by extensive spectroscopic analysis as well as nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculations. All the compounds were assayed for their antibacterial activity. Among them, compounds 4, 8, and 12 exhibited remarkable inhibition against Listeria monocytogenes with minimum inhibitory concentrations (MIC) values ranging from 8 mu g & sdot;mL- 1 to 64 mu g & sdot;mL- 1, and displayed moderate inhibition against methicillin-resistant Staphylococcus aureus (MRSA) with MIC value of 64 mu g & sdot;mL- 1. Compounds 4, 8, 9, and 12 showed moderate inhibition activities against both Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 32 mu g & sdot;mL- 1 to 128 mu g & sdot;mL- 1.
摘要：
The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the most common method of tumor treatment. Different intrinsic cellular mechanisms affect the response of cells to ionizing radiation (IR) and the effectiveness of cancer radiotherapy. In this review, we summarize and discuss recent advances in understanding the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage and in determining the outcomes of cancer radiotherapy. Insights into RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy and radioprotection of normal tissues.
期刊：
Biosensors and Bioelectronics,2024年252:116149 ISSN：0956-5663
通讯作者：
Hongfen Yang<&wdkj&>Ren Cai
作者机构：
[Zhang, Chunxiao; Lyu, Yifan; Wang, Futing; Tan, Weihong] Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Material Science and Engineering, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082, China;[Deng, Suping] Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, China;[Zhang, Penghui; Jiang, Yifei] The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China;[Yang, Hongfen] Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, China. Electronic address: yanghf88@gmail.com;[Xiang, Li] Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Material Science and Engineering, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082, China. Electronic address: xiangli@pku.edu.cn
通讯机构：
[Hongfen Yang] H;[Ren Cai] M;Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, China<&wdkj&>Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Material Science and Engineering, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082, China
关键词：
Double-response 3D DNA nanomachine;High efficiency;Hybridization chain reactions;Laser-scribed graphene;Real-time monitor
摘要：
The microRNA-21 is closely related to chromatin remodeling and epigenetic regulation. In this work, an efficient double-response 3D DNA nanomachine (DRDN) was assembled by co-immobilizing two different lengths of hairpin DNA on the surface of gold nanoparticles (AuNPs) to capture microRNA-21 (miRNA-21), recycle miRNA-21, and trigger hybridization chain reactions (HCR). This work reports the fabrication of a laser-scribed graphene (LSG) electrode with excellent flexibility and electrical conductivity by laser-scribing commercial polyimide films (PI). The as-proposed self-powered biosensing platform presents significantly increased instantaneous current to in real-time monitor miRNA-21 by a capacitor. The biosensing platform exhibited highly sensitive detection of miRNA-21 with a detection limit of 0.142fM in the range of 0.5fM to 1×10(4)fM, and demonstrated high efficiency in the analysis of the tumor markers.
期刊：
International Journal of Biological Macromolecules,2024年259(Pt 1):129104 ISSN：0141-8130
通讯作者：
Liu, Y
作者机构：
[Liu, Yu; Zhang, Shaoqi; Li, Le; Zhen, Deshuai; Yang, Aofeng] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.;[Liu, Yu; Zhang, Shaoqi; Zhen, Deshuai] Hunan Univ, Sch Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;[Grimes, Craig A.] Flux Photon Corp, 5950 Shiloh Rd East, Alpharetta, GA 30005 USA.;[Liu, Yu] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.
通讯机构：
[Liu, Y ] H;Hunan Univ, Sch Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.
关键词：
Covalent organic framework;Fluorescent probe;In vivo imaging
摘要：
Simple and accurate in vivo monitoring of Fe(3+) is essential for gaining a better understanding of its role in physiological and pathological processes. A novel fluorescent probe was synthesized via in situ solid-state polymerization of 3,4-ethylenedioxythiophene (PEDOT) in the pore channels of a covalent organic framework (COF). The PEDOT@COF fluorescent probe exhibited an absolute quantum yield (QY) 3 times higher than COF. In the presence of Fe(3+) the PEDOT@COF 475nm fluorescence emission, 365nm excitation, is quenched within 180s. Fluorescence quenching is linear with Fe(3+) in the concentration range of 0-960μM, with a detection limit of 0.82μM. The fluorescence quenching mechanism was attributed to inner filter effect (IEF), photoinduced electron transfer (PET) and static quenching (SQE) between PEDOT@COF and Fe(3+). A paper strip-based detector was designed to facilitate practical applicability, and the PEDOT@COF probe successfully applied to fluorescence imaging of Fe(3+) levels in vivo. This work details a tool of great promise for enabling detailed investigations into the role of Fe(3+) in physiological and pathological diseases.
摘要：
Microcystins are highly toxic cyanotoxins and have been produced worldwide with the global expansion of harmful cyanobacterial blooms (HABs), posing serious threats to human health and ecosystem safety. Yet little knowledge is available on the underlying process occurring in the aquatic environment with microcystins. Microplastics as vectors for pollutants has received growing attention and are widely found co-existing with microcystins. On the one hand, microplastics could react with microcystins by adsorption, altering their environmental behavior and ecological risks. On the other hand, particular attention should be given to microplastics due to their implications on the outbreak of HABs and the generation and release of microcystins. However, limited reviews have been undertaken to link the co-existing microcystins and microplastics in natural water. This study aims to provide a comprehensive understanding on the environmental relevance of microcystins and microplastics and their potential interactions, with particular emphasis on the adsorption, transport, sources, ecotoxicity and environmental transformation of microcystins affected by microplastics. In addition, current knowledge gaps and future research directions on the microcystins and microplastics are presented. Overall, this review will provide novel insights into the ecological risk of microcystins associated with microplastics in real water environment and lay foundation for the effective management of HABs and microplastic pollution.
通讯机构：
[Yang, SY; Li, L ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Hlth Inspect & Quarantine, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.
摘要：
Mercury is a highly toxic element that is widely present in all types of environmental media and can accumulate in living organisms. Prolonged exposure to high levels of mercury can lead to brain damage and death, so the detection of mercury is of great importance. In this study, a cost-effective and easy-to-operate electrochemical sensing method was successfully developed based on an amino-functionalized titanium-based MXene (NH(2)-Ti(3)C(2)T(x)) for the rapid and selective detection of Hg(2+) that could have a coordination effect with the -NH(2) group of NH(2)-Ti(3)C(2)T(x) to promote the efficient accumulation of Hg(2+). In this strategy, the NH(2)-Ti(3)C(2)T(x) was first modified on glassy carbon electrodes (GCE) to fabricate the electrochemical sensor. Benefiting from the excellent electrical conductivity, abundant active sites, and strong adsorption capacity performance of the NH(2)-Ti(3)C(2)T(x), the NH(2)-Ti(3)C(2)T(x) modified GCE (NH(2)-Ti(3)C(2)T(x)/GCE) exhibited satisfactory selectivity and enhanced square wave anodic stripping voltammetry (SWASV) measurement for the rapid detection of trace amounts of Hg(2+) in aqueous solutions. The electrochemical sensor was found to be capable of detecting Hg(2+) with a low detection limit of 8.27 nmol L(-1) and a linear range of 0.5 μmol L(-1) to 50 μmol L(-1). The response time of the electrochemical sensing method was 308 s. In addition, the electrochemical sensing method has good selectivity, repeatability and stability, and multiple heavy metal ions have no effect on its detection, with repeatability and stability RSDs of 1.68% and 1.43%, respectively. Furthermore, the analysis of practical water samples demonstrated that the developed method was highly practical for the actual determination of Hg(2+) with recoveries in the range of 99.22-101.90%.
作者机构：
[Gao, Shuaining; Chen, Shi] School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan Province, 421001, P. R. China;[Luo, Jinhua; Huang, Xin; Gao, Shuaining; Guo, Hejiang; Han, Yang; Chen, Shi; Li, Saiyu; Xie, Da-Fei] Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R. China;[Li, Saiyu] School of Life Sciences, Hebei University, Baoding, Hebei Province, 071002, P. R. China;[Luo, Jinhua] Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan, 410078, P. R. China;[Guan, Hua] School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan Province, 421001, P. R. China. ghlsh@163.com
通讯机构：
[Hua Guan; Ping-Kun Zhou] S;[Ruixue Huang] D;Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, P. R. China<&wdkj&>School of Public Health, Hengyang Medical School, University of South China, Hengyang, P. R. China<&wdkj&>Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, P. R. China
摘要：
Metabolic reprogramming, a hallmark of cancer, is closely associated with tumor development and progression. Changes in glycolysis play a crucial role in conferring radiation resistance to tumor cells. How radiation changes the glycolysis status of cancer cells is still unclear. Here we revealed the role of TAB182 in regulating glycolysis and lactate production in cellular response to ionizing radiation. Irradiation can significantly stimulate the production of TAB182 protein, and inhibiting TAB182 increases cellular radiosensitivity. Proteomic analysis indicated that TAB182 influences several vital biological processes, including multiple metabolic pathways. Knockdown of TAB182 results in decreased lactate production and increased pyruvate and ATP levels in cancer cells. Moreover, knocking down TAB182 reverses radiation-induced metabolic changes, such as radioresistant-related lactate production. TAB182 is necessary for activating LDHA transcription by affecting transcription factors SP1 and c-MYC; its knockdown attenuates the upregulation of LDHA by radiation, subsequently suppressing lactate production. Targeted suppression of TAB182 significantly enhances the sensitivity of murine xenograft tumors to radiotherapy. These findings advance our understanding of glycolytic metabolism regulation in response to ionizing radiation, which may offer significant implications for developing new strategies to overcome tumor radioresistance.
摘要：
The immune response to Mycoplasma pneumoniae infection plays a key role in clinical symptoms. Previous investigations focused on the pro-inflammatory effects of leukocytes and the pivotal role of epithelial cell metabolic status in finely modulating the inflammatory response have been neglected. Herein, we examined how glycolysis in airway epithelial cells is affected by M. pneumoniae infection in an in vitro model. Additionally, we investigated the contribution of ATP to pulmonary inflammation. Metabolic analysis revealed a marked metabolic shift in bronchial epithelial cells during M. pneumoniae infection, characterized by increased glucose uptake, enhanced aerobic glycolysis, and augmented ATP synthesis. Notably, these metabolic alterations are orchestrated by adaptor proteins, MyD88 and TRAM. The resulting synthesized ATP is released into the extracellular milieu via vesicular exocytosis and pannexin protein channels, leading to a substantial increase in extracellular ATP levels. The conditioned medium supernatant from M. pneumoniae-infected epithelial cells enhances the secretion of both interleukin (IL)-1β and IL-18 by peripheral blood mononuclear cells, partially mediated by the P2X7 purine receptor (P2X7R). In vivo experiments confirm that addition of a conditioned medium exacerbates pulmonary inflammation, which can be attenuated by pre-treatment with a P2X7R inhibitor. Collectively, these findings highlight the significance of airway epithelial aerobic glycolysis in enhancing the pulmonary inflammatory response and aiding pathogen clearance.
摘要：
This article provides an overview of the background knowledge of ferroptosis in the nervous system, as well as the key role of nuclear factor E2-related factor 2 (Nrf2) in regulating ferroptosis. The article takes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as the starting point to explore the close association between Nrf2 and ferroptosis, which is of clear and significant importance for understanding the mechanism of neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links ferroptosis to the pathogenesis of NDs. As the disease progresses, damage to the antioxidant system, excessive OS, and altered Nrf2 expression levels, especially the inhibition of ferroptosis by lipid peroxidation inhibitors and adaptive enhancement of Nrf2 signaling, demonstrate the potential clinical significance of Nrf2 in detecting and identifying ferroptosis, as well as targeted therapy for neuronal loss and mitochondrial dysfunction. These findings provide new insights and possibilities for the treatment and prevention of NDs.
期刊：
Science of The Total Environment,2024年916:170342 ISSN：0048-9697
通讯作者：
Liang, GY;Chen, ZZ
作者机构：
[Liang, GY; Yin, Lihong; Pu, Yuepu; Liang, Geyu; Ge, Yiling; Zhang, Tianyi; Fang, Yifei; Yang, Sheng; Zhu, Yuxin; Wan, Xin; Hu, Chengyu; Gong, Saisai] Southeast Univ, Sch Publ Hlth, Key Lab Environm Med Engn, Minist Educ, Nanjing, Peoples R China.;[Chen, Zaozao; Chen, ZZ] Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Nanjing, Peoples R China.;[Yang, Fei] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Epidemiol & Hlth Stat,Key Lab Typ Environm Po, Hengyang, Peoples R China.
通讯机构：
[Liang, GY ; Chen, ZZ ] S;Southeast Univ, Sch Publ Hlth, Key Lab Environm Med Engn, Minist Educ, Nanjing, Peoples R China.;Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Nanjing, Peoples R China.
关键词：
AOP framework;Ferroptosis;Inhalation exposure;Liver injury and fibrosis;Nanoplastics
摘要：
The emerging contaminant nanoplastics (NPs) have received considerable attention. Due to their tiny size and unique colloidal properties, NPs could more easily enter the body and cross biological barriers with inhalation exposure. While NPs -induced hepatotoxicity has been reported, the hepatic impact of inhaled NPs was still unknown. To close this gap, a 40 nm polystyrene NPs (PS -NPs) inhalation exposure mice model was developed to explore the hepatotoxicity during acute (1 week), subacute (4 weeks), and subchronic period (12 weeks), with four exposure doses (0, 16, 40, and 100 mu g/day). Results showed that inhaled PS -NPs caused a remarkable increase of ALT, AST, and ALP with a decrease of CHE, indicating liver dysfunction. Various histological abnormalities and significantly higher levels of inflammation in a dose- and time -dependent manner were observed. Moreover, after 4 weeks and 12 weeks of exposure, Masson staining and upregulated expression of TGF-beta, alpha-SMA, and Col1a1 identified that inhaled PS -NPs exposure triggered the progression of liver fibrosis with the exposure time prolonged. From the mechanistic perspective, transcriptome analysis revealed that ferroptosis was involved in PS -NPs -induced liver hepatotoxicity, and key features of ferroptosis were detected, including persistent oxidative stress, iron overload, increased LPO, mitochondria damage, and the expression changes of GPX4, TFRC, and Ferritin. And in vitro and in vivo recovery tests showed that ferroptosis inhibitor Fer-1 treatment alleviated liver injury and fibrosis. The above results confirmed the critical role of ferroptosis in PS -NPs -induced hepatotoxicity. Furthermore, to better conclude our findings and understand the mechanistic causality within it, an adverse outcome pathway (AOP) framework was established. In total, this present study conducted the first experimental assessment of inhalation exposure to PS -NPs on the liver, identified that continuous inhaled PS -NPs could cause liver injury and fibrosis, and PS -NPs- ferroptosis provided a novel mechanistic explanation.
期刊：
Science of The Total Environment,2023年905:167167 ISSN：0048-9697
通讯作者：
Liu, J
作者机构：
Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Inst Cytol & Genet,Dept Cell Biol & Genet,Key Lab, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Hunan, Peoples R China.;[Liu, Jun] 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Liu, J ] 2;28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Liver;MCs;Mechanisms;Toxicity
摘要：
Microcystins (MCs) are a class of biologically active cyclic heptapeptide pollutants produced by the freshwater alga Microcystis aeruginosa. With increased environmental pollution, MCs have become a popular research topic. In recent years, the hepatotoxicity of MCs and associated effects and mechanisms have been studied extensively. Current epidemiological data indicate that long-term human exposure to MCs can lead to severe liver toxicity, acute toxicity, and death. In addition, current toxicological studies on the liver, a vital target organ of MCs, indicate that MC contamination is associated with the development of liver cancer, nonalcoholic fatty liver, and liver fibrosis. MCs produce hepatotoxicity that affects the metabolic homeostasis of the liver, induces apoptosis, and acts as a pro-cancer factor, leading to liver lesions. MCs mainly mediate the activation of signaling pathways, such as the ERK/JNK/p38 MAPK and IL-6-STAT3 pathways, which leads to oxidative damage and even carcinogenesis. Moreover, MCs can act synergistically with other pollutants to produce combined toxicity. However, few systematic reviews have been performed on these new findings. This review systematically summarizes the toxic effects and mechanisms of MCs on the liver and discusses the combined liver toxicity effects of MCs and other pollutants to provide reference for subsequent research. The toxicity of different MC isomers deserves further study. The detection methods and limit standards of MCs in agricultural and aquatic products will represent important research directions in the future. Standard protocols for fish sampling during harmful algal blooms or to evaluate the degree of MC toxicity in nature are lacking. In future, bioinformatics can be applied to offer insights into MC toxicology research and potential drug development for MC poisoning. Further research is essential to understand the molecular mechanisms of liver function damage in combined-exposure toxicology studies to establish treatment for MC-induced liver damage.
摘要：
BACKGROUND: Nanoplastics (NPs) could be released into environment through the degradation of plastic products, and their content in the air cannot be ignored. To date, no studies have focused on the cardiac injury effects and underlying mechanisms induced by respiratory exposure to NPs. RESULTS: Here, we systematically investigated the cardiotoxicity of 40nm polystyrene nanoplastics (PS-NPs) in mice exposed via inhalation. Four exposure concentrations (0µg/day, 16µg/day, 40µg/day and 100µg/day) and three exposure durations (1 week, 4 weeks, 12 weeks) were set for more comprehensive information and RNA-seq was performed to reveal the potential mechanisms of cardiotoxicity after acute, subacute and subchronic exposure. PS-NPs induced cardiac injury in a dose-dependent and time-dependent manner. Acute, subacute and subchronic exposure increased the levels of injury biomarkers and inflammation and disturbed the equilibrium between oxidase and antioxidase activity. Subacute and subchronic exposure dampened the cardiac systolic function and contributed to structural and ultrastructural damage in heart. Mechanistically, violent inflammatory and immune responses were evoked after acute exposure. Moreover, disturbed energy metabolism, especially the TCA cycle, in the myocardium caused by mitochondria damage may be the latent mechanism of PS-NPs-induced cardiac injury after subacute and subchronic exposure. CONCLUSION: The present study evaluated the cardiotoxicity induced by respiratory exposure to PS-NPs from multiple dimensions, including the accumulation of PS-NPs, cardiac functional assessment, histology observation, biomarkers detection and transcriptomic study. PS-NPs resulted in cardiac injury structurally and functionally in a dose-dependent and time-dependent manner, and mitochondria damage of myocardium induced by PS-NPs may be the potential mechanism for its cardiotoxicity.
