Ecotoxicology and Environmental Safety最新文献

{"title":"Associations of exposure to phthalate with serum uric acid and hyperuricemia risk, and the mediating role of systemic immune inflammation","authors":"Zhiping Niu ,&nbsp;Tianyi Chen ,&nbsp;Zhizhou Duan ,&nbsp;Shichao Han ,&nbsp;Yifan Shi ,&nbsp;Wenyuan Yu ,&nbsp;Shuang Du ,&nbsp;Hao Tang ,&nbsp;Wenpu Shao ,&nbsp;Jin Sun ,&nbsp;Han Chen ,&nbsp;Yunfei Cai ,&nbsp;Yanyi Xu ,&nbsp;Zhuohui Zhao","doi":"10.1016/j.ecoenv.2024.117269","DOIUrl":"10.1016/j.ecoenv.2024.117269","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies found that urinary phthalates (PAEs) metabolites may be associated with increased serum uric acid concentration and hyperuricemia risk. However, no population-based study has investigated the underlying biological mechanisms.</div></div><div><h3>Methods</h3><div>This nationwide cross-sectional study analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2003–2018. Urinary PAEs metabolites were measured and 8 PAEs metabolites (MCPP, MECPP, MEHHP, MEOHP, MBzP, MiBP, MBP, and MEP) were incorporated into the analysis. Serum uric acid was determined and hyperuricemia cases were identified. Multi-variable generalized linear model, exposure-response (E-R) function and weighted quantile sum (WQS) regression were utilized to investigate the relationships of PAEs metabolites with serum uric acid concentration and hyperuricemia risk. Systemic immune inflammation (SII) was assessed using the SII index and its mediation effects were explored using causal mediation effect model.</div></div><div><h3>Results</h3><div>Data from 10,633 US adults in the NHANES 2003–2018 was analyzed. Except for MEP, individual PAEs metabolite and total PAEs metabolites were associated with increased serum uric acid concentration and hyperuricemia risk. E-R function of PAEs metabolites with serum uric acid concentration and the risk of hyperuricemia showed significantly positive associations with most curves in a nearly linear relationship. WQS regression showed that the mixture of PAEs metabolites was related to elevated serum uric acid and hyperuricemia risk, and MBzP was identified as the most contributing PAEs metabolite. The causal mediation effect model found that SII significantly mediated the relationships of PAEs metabolites with serum uric acid and hyperuricemia risk.</div></div><div><h3>Conclusion</h3><div>Individual and mixture of urinary PAEs metabolites were associated with increased serum uric acid concentration and the risk of hyperuricemia. MBzP exhibited the highest contribution to the overall effects. SII alteration may be an important biological mechanism underlining the impact of PAEs metabolites on serum uric acid concentration and hyperuricemia risk.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117269"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant and renal protective effects of Nano-selenium on adenine-induced acute renal failure in canines","authors":"Mengdi Zhang ,&nbsp;Jindong Gao ,&nbsp;Md. F. Kulyar ,&nbsp;Wanhe Luo ,&nbsp;Guodong Zhang ,&nbsp;Xiaoqi Yang ,&nbsp;Tianguang Zhang ,&nbsp;Haihang Gao ,&nbsp;Yuxuan Peng ,&nbsp;Jiabin Zhang ,&nbsp;Muhammad Altaf ,&nbsp;Samah Attia Algharib ,&nbsp;Donghai Zhou ,&nbsp;Jianzhong He","doi":"10.1016/j.ecoenv.2024.117274","DOIUrl":"10.1016/j.ecoenv.2024.117274","url":null,"abstract":"<div><div>Acute renal failure is a common clinical disease in canines, affecting antioxidant levels and decreasing the body's resistance. This study aims to explore the therapeutic mechanism of Nano-selenium in acute renal failure. The histopathological and imaging changes of kidney tissue were observed with the gene and protein expression levels of Keap1, Nrf2, HO-1, and NQO1 in the kidney. According to our findings, adding nano-selenium can effectively reduce the concentration of CRE and BUN in blood and kidney tissues. It increased the activity of GSH-PX and SOD by an effective reduction of MDA. Through pathological and imaging observations, it was found that adding nano-selenium could improve the kidney tissue structure of acute renal failure. The results of the RT-qPCR experiment showed that after the addition of nano-selenium, the mRNA expression of the Keap1 gene decreased significantly. In contrast, the mRNA expression of the Nrf2, HO-1, and NQO1 genes increased significantly. The experimental results were further verified by western blot and immunohistochemical analysis. Hence, the nano-selenium intervention improved kidney function and increased antioxidant levels in canines suffering from acute renal failure with the involvement of the Keap1-Nrf2/ARE signaling pathway.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117274"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between blue space exposure and rheumatoid arthritis: The modifying effect of genetic susceptibility and air pollutants","authors":"Yi-Sheng He ,&nbsp;Man Ge ,&nbsp;Yi-Qing Xu ,&nbsp;Zhao-Xing Gao ,&nbsp;Tian He ,&nbsp;Peng Zhang ,&nbsp;Sha-Sha Tao ,&nbsp;Peng Wang ,&nbsp;Zhu Chen ,&nbsp;Hai-Feng Pan","doi":"10.1016/j.ecoenv.2024.117346","DOIUrl":"10.1016/j.ecoenv.2024.117346","url":null,"abstract":"<div><div>Studies on the interaction among genetic susceptibility, blue space exposure, and rheumatoid arthritis (RA) risk have been lacking. Therefore, we examined the association between blue space exposure and RA incidence and assess the modifying effect of genetic susceptibility and air pollutants. Form the UK Biobank, 322,783 participants without RA were enrolled in this study. The association between blue space exposure and RA incidence was estimated using a cox proportional hazards model. The combined effect of blue space and genetic factors on the risk of RA was further evaluated. The polygenic risk score (PRS) for RA was calculated to represent individual genetic risk, and the potential modification effect of air pollution on the relationship between blue space, PRS, and RA were explored. During a median follow-up of 12.4 years, 3659 RA cases were identified. A 10 % increase in blue space_300 m was associated with a 22.6 % reduction in RA incidence (HR=0.774, 95 % CI: 0.670, 0.895), exhibiting a consistent downward trend in the exposure-response curve. A high PRS was an independent risk factor for RA (HR=1.393, 95 % CI: 1.347, 1.439). The associations between blue space exposure, PRS, and the risk of RA were dose-dependent, with the lowest risk observed among those with high levels of blue space and lower PRS (HR_{bluespace300m}=0.501, 95 % CI: 0.431, 0.583; HR_{bluespace1000m}=0.476, 95 % CI: 0.408, 0.555). Interaction analysis indicated that increased concentrations of air pollutants strengthened the relationship between PRS and RA. Blue space exposure mitigated the risk of RA development, particularly in individuals with low genetic risk.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117346"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of adverse outcome pathway, potency, human exposure supports carcinogenicity of polyhexamethylene guanidine phosphate in lung cancer","authors":"Yong Joo Park ,&nbsp;Ha Ryong Kim ,&nbsp;Jun Woo Kim ,&nbsp;Jong-Hyun Lee ,&nbsp;Younghee Kim ,&nbsp;Jungyun Lim ,&nbsp;Yong-Wook Baek ,&nbsp;Kyu Hyuck Chung","doi":"10.1016/j.ecoenv.2024.117222","DOIUrl":"10.1016/j.ecoenv.2024.117222","url":null,"abstract":"<div><div>In this study, we investigated the potential mechanisms by which polyhexamethylene guanidine phosphate (PHMG-p), a known respiratory irritant, may contribute to lung cancer development. Using the adverse outcome pathway (AOP) framework, we analyzed established databases (such as AOP-Wiki) and employed AI tools (AOP-helpFinder) to identify key events (KEs) associated with lung carcinogenesis. Our analysis indicates that chronic inhalation of PHMG-p triggers a non-genotoxic pathway, characterized by cell membrane disruption, inflammation, and oxidative stress, with a point of departure (POD) of 0.0018 mg/m³, suggesting carcinogenic potential. Additionally, a human exposure assessment revealed that most claimants were exposed to PHMG-p levels exceeding the estimated inhalation reference concentration (RfC) of 0.018 µg/m³. While downstream KEs, such as DNA damage, mutation, and cell proliferation, require further investigation, our findings, supported by the AOP framework and potency and exposure assessments, strongly suggest that PHMG-p exposure could induce lung cancer in individuals affected by humidifier disinfectants. These results underscore the importance of a comprehensive risk assessment approach for evaluating the carcinogenicity of PHMG-p.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117222"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to particulate matter (PM2.5) weakens corneal defense by downregulating thrombospondin-1 and tight junction proteins","authors":"Liangliang Niu ,&nbsp;Jiamin Liu ,&nbsp;Huan Xu ,&nbsp;Binghui Liu ,&nbsp;Maomao Song ,&nbsp;Chunchun Hu ,&nbsp;Rui Jiang ,&nbsp;Xinghuai Sun ,&nbsp;Yuan Lei","doi":"10.1016/j.ecoenv.2024.117276","DOIUrl":"10.1016/j.ecoenv.2024.117276","url":null,"abstract":"<div><h3>Background</h3><div>Fine particulate matter (PM_2.5) induces ocular surface toxicity through pyroptosis, oxidative stress, autophagy, and inflammatory responses. However, the precise molecular pathways through which PM_2.5 causes corneal damage remain unclear. This study aims to investigate the underlying mechanisms by exposing human corneal epithelial cells (HCECs) to PM_2.5.</div></div><div><h3>Methods</h3><div>After the morphology and chemical composition analysis of the PM samples, we conducted both in vivo and in vitro experiments to investigate PM_2.5-induced corneal epithelial damage. We assessed corneal barrier function in HCECs using transepithelial electrical resistance (TEER) assays. To explore the molecular mechanisms of PM_2.5-induced corneal epithelial damage, we performed whole-transcriptome resequencing, quantitative RT-PCR, and western blotting in vitro. In addition, we analyzed mouse corneas exposed to concentrated ambient PM_2.5 through immunofluorescence staining to observe the resulting changes in corneal epithelial protein expression in vivo.</div></div><div><h3>Results</h3><div>Our results showed significant impairment of corneal epithelial barrier function in PM_2.5-treated HCECs, as indicated by decreased TEER values. The expression of thrombospondin-1 (THBS1) and claudin-1, both key factors for maintaining corneal epithelial barrier integrity, was markedly reduced at the gene and protein levels in both in vitro and in vivo PM_2.5 exposure models. Moreover, the levels of tight junction-associated proteins, including occludin, zonula occludens-1 (ZO-1) and ZO-2, essential components of the corneal epithelial barrier, were significantly diminished in PM_2.5-treated HCECs.</div></div><div><h3>Conclusion</h3><div>PM_2.5 exposure leads to corneal epithelium damage by disrupting tight junction proteins and THBS1 expression. These findings provide insight into potential pathways for PM_2.5-induced ocular toxicity and underscore the need for protective strategies against such environmental pollutants.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117276"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrochlorothiazide disrupts DNA damage response to exacerbate skin photosensitivity","authors":"Lei Tao ,&nbsp;Yujiao Xu ,&nbsp;Yingyue Cui ,&nbsp;Qingcheng Wei ,&nbsp;Boyang Lin ,&nbsp;Yu Cao ,&nbsp;Zhen Dai ,&nbsp;Zhi Ma ,&nbsp;Ling Zhang ,&nbsp;Aiping Shi ,&nbsp;Ling Gu ,&nbsp;Yunyao Liu","doi":"10.1016/j.ecoenv.2024.117314","DOIUrl":"10.1016/j.ecoenv.2024.117314","url":null,"abstract":"<div><div>Hydrochlorothiazide (HCTZ) is a widely utilized diuretic for the treatment of hypertension. The photosensitivity of HCTZ has been recognized for six decades, with UVA being considered the primary culprit. However, the precise molecular mechanism of HCTZ sensitizing skin to UV radiation remains unknown. In this study, we demonstrate that HCTZ exacerbates UVB-induced photosensitivity in normal skin by disrupting the DNA damage response, a crucial network responsible for maintaining epidermal homeostasis. Here, we found that HCTZ aggravates UVB-induced mouse skin damage. Through transcriptomic and proteomic profiling, we have found that the cell cycle and p53 signaling pathway may contribute to the photosensitivity caused by HCTZ. In keratinocytes, HCTZ promotes the transition from G1 to S phase and inhibits the p53 signaling pathway after exposure to UV radiation. We have found that HCTZ enhances the accumulation of DNA damage induced by UVB and impairs nucleotide excision repair (NER), which is responsible for repairing UVB-induced DNA lesions, by inhibiting the expression of NER-related genes and shortening the duration of G1 phase. Furthermore, pharmacologically inducing G1 arrest eliminates HCTZ-induced accumulation of damaged DNA. These findings unveil an unknown mechanism through which HCTZ impairs NER and interferes with UVB-induced cell cycle arrest, ultimately leading to improper response towards DNA damage and increased skin sensitivity.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117314"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlorophenols in environment: Recent updates on pretreatment and analysis methods","authors":"Min Qian ,&nbsp;Qi An ,&nbsp;Yu Bian ,&nbsp;Meng Zhang ,&nbsp;Xue-song Feng ,&nbsp;Cheng Du","doi":"10.1016/j.ecoenv.2024.117326","DOIUrl":"10.1016/j.ecoenv.2024.117326","url":null,"abstract":"<div><div>Chlorophenols (CPs) are widely used in industries such as petrochemicals, insecticides, pharmaceuticals, synthetic dyes and wood preservatives. However, owing to the improper discharge and disposal, they have become major contaminants that are ubiquitously distributed in water, soil, and sewage sediments, posing a significant threat to ecosystems and human health. Consequently, accurate, sensitive and effective pretreatment and analysis methods for CPs are urgently required and have been actively explored in recent years. This review encompasses the pretreatment and detection methods for CPs in environmental samples from 2010 to 2024. The pretreatment methods for CPs primarily include solid-phase extraction, liquid-liquid extraction, solid-phase microextraction, liquid-phase microextraction, and QuEChERS. These methods are evolving towards more effective and environmentally friendly technologies, such as the miniaturization and automation of equipment, the development of innovative materials (including graphene, molecularly imprinted polymers, layered double hydroxides, porous organic polymers, and porous carbon), and the use of green solvents like deep eutectic solvents. Detection methods emphasize liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, sensors, and capillary electrophoresis. Advances in chromatographic columns, novel ion sources, and high-resolution mass spectrometry have significantly improved detection performance. In addition, the pros and cons of diverse techniques, critical comments and future perspectives are elaborated.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117326"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ambient PMs pollution, blood pressure, potential mediation by short-chain fatty acids: A prospective panel study of young adults in China","authors":"Xin Chou ,&nbsp;Miao Fang ,&nbsp;Yue Shen ,&nbsp;Cunzhong Jiang ,&nbsp;Lin Miao ,&nbsp;Liyan Yang ,&nbsp;Zexi Wu ,&nbsp;Xiangyu Yao ,&nbsp;Kunpeng Ma ,&nbsp;Kun Qiao ,&nbsp;Zhijing Lin","doi":"10.1016/j.ecoenv.2024.117316","DOIUrl":"10.1016/j.ecoenv.2024.117316","url":null,"abstract":"<div><h3>Background</h3><div>The concurrent effects of particulate matter (PM) on both blood pressure (BP) and short-chain fatty acids (SCFAs) are insufficiently explored, with limited research on the potential mediating roles of SCFAs.</div></div><div><h3>Methods</h3><div>In this prospective panel study with 4 follow-ups, we recruited 40 college students in Hefei, China, to assess the impacts of short-term exposure to PM (aerodynamic diameter ≤10 μm (PM₁₀), ≤2.5 μm (PM_2.5), and ≤1 μm (PM₁)) on BP and SCFAs, along with potential mechanisms. Real-time PM data, urinary SCFAs levels, and BP indicators were systematically collected. Linear mixed-effects models assessed the relationships between PM, SCFAs, and BP. Mediation analyses explored SCFAs’ mediating role in the PM-BP association.</div></div><div><h3>Results</h3><div>PM exposure was positively linked to BP and negatively associated with SCFAs. For a 10 μg/m³ rise in PM₁₀ at lag 0–72 h, there were notable reductions of 0.0019 % (95 %CI: −0.0028, −0.0010) in Acetic acid, 0.0262 % (-0.0369, −0.0155) in Propionic acid, and 0.0702 % (-0.1025, −0.0378) in Butyric acid. Systolic BP, diastolic BP, and mean arterial pressure (MAP) increased by 2.60 mmHg (0.96, 4.25), 2.24 mmHg (1.18, 3.31), and 2.36 mmHg (1.20, 3.53), respectively, per 10-μg/m³ rise in PM₁ at lag 0–24 h. Decreased SCFAs levels explained significant portions (24.69–31.80 %) of the elevated MAP due to PM₁₀. Stronger associations were found in females and individuals with abnormal BMI.</div></div><div><h3>Conclusions</h3><div>Our study shows that PM exposure decreases urinary SCFAs levels, which partially mediate the impact of PM on elevated BP. These findings enhance our comprehension of the pathways linking PM exposure to BP changes.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117316"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium protects mouse spermatogonia against ivermectin-induced apoptosis by alleviating endoplasmic reticulum stress in vitro","authors":"Daniel Chavez Varias,&nbsp;Sung-Hwan Moon,&nbsp;Seung Hee Shin,&nbsp;Buom-Yong Ryu","doi":"10.1016/j.ecoenv.2024.117307","DOIUrl":"10.1016/j.ecoenv.2024.117307","url":null,"abstract":"<div><div>Ivermectin (IVM) is a widely used anthelmintic in human and veterinary medicine. However, the increasing use of IVM raises concerns about its potential harm against non-targeted organisms. This study demonstrates a novel mechanism where IVM triggers apoptosis via endoplasmic reticulum (ER) stress in GC-1 spg <em>in vitro</em>. The inhibitory effects of selenium (Se) against the toxicological mechanism were also explored. IVM dose-dependently induces oxidative stress, dysregulated Ca²⁺ levels, and intracellular protein aggregation. Increased mitochondria-associated ER membrane (MAM) activity through Glucose-regulated Protein 75 (Grp75) overloads the mitochondria with Ca²⁺, causing mitochondrial dysfunction. These simultaneous stressors lead to unfolded protein response and apoptosis. Se reverses all these subcellular events by promoting the expression of selenoprotein-encoding genes to maintain the ER and redox homeostasis. The testis-enriched Glutathione Peroxidase 4 (<em>Gpx4</em>) and the testis-specific Selenoprotein V (<em>Selenov</em>) are only upregulated in the IVM and Se co-treatment group, suggesting their potential role in stress response. These findings confirm that toxic doses of IVM lead to programmed cell death in type B spermatogonia through redox imbalance-associated ER stress. This study provides valuable insights into refining male reproductive toxicity evaluation, targeting of ER stress to protect male germ cells, and maintaining male fertility from IVM-induced toxicity.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117307"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MANF inhibits NLRP3 inflammasome activation by competitively binding to DDX3X in paraquat-stimulated alveolar macrophages","authors":"Yi Pu ,&nbsp;Siying Han ,&nbsp;Jie Chen ,&nbsp;Zhenning Liu","doi":"10.1016/j.ecoenv.2024.117331","DOIUrl":"10.1016/j.ecoenv.2024.117331","url":null,"abstract":"<div><div>NLRP3 inflammasome activation in macrophages is involved in paraquat-induced acute lung injury (ALI). MANF exerts an inhibitory effect against inflammation and cell death. The aim of this study was to investigate the role of MANF in paraquat-stimulated alveolar macrophages and the potential mechanism. Paraquat-induced ALI mouse model was established by intraperitoneally injection of 30 mg/kg of paraquat. The lung pathological changes were observed by hematoxylin and eosin staining. The expression of MANF/DDX3X/NLRP3/Caspase-1 in mice lung macrophages was evaluated by double immunofluorescence staining and western blot. NLRP3 inflammasome activation and pro-inflammatory cytokines (IL-1β and IL-18) in paraquat-stimulated macrophage transfected with MANF overexpression plasmid (pcDNA3.1-MANF) or siRNA-MANF were measured by Western blot. The protein–protein interaction of MANF/DDX3X/NLRP3 was verified by Co-immunoprecipitation. As a result, MANF/DDX3X/NLRP3/Caspase-1 were upregulated in alveolar macrophages of paraquat-induced ALI in mice. In paraquat-stimulated alveolar macrophages, upregulation of MANF and DDX3X were also observed, accompanied by NLRP3 inflammasome activation. In addition, overexpression of MANF inhibited NLRP3 inflammasome activation in paraquat-stimulated alveolar macrophages. In contrast, knockdown of MANF aggravated NLRP3 inflammasome activation. Co-immunoprecipitation results revealed that DDX3X could bind to MANF and NLRP3, but MANF could not bind to NLRP3 in paraquat-stimulated alveolar macrophages. Furthermore, Co-immunoprecipitation of truncated three fragments of DDX3X confirmed MANF can interact with the helicase core of DDX3X which is the binding site for NLRP3. Taken together, MANF exerted a protective effect against paraquat-induced cytotoxicity by inhibiting the NLRP3 inflammasome activation in macrophages via competitive binding to the helicase core of DDX3X.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"287 ","pages":"Article 117331"},"PeriodicalIF":6.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}