Human & experimental toxicology最新文献

{"title":"Insights into therapeutic potential and practical applications of natural toxins from poisonous mushrooms.","authors":"Tharuka Wijesekara, Baojun Xu","doi":"10.1177/09603271251323134","DOIUrl":"10.1177/09603271251323134","url":null,"abstract":"<p><p>IntroductionMushrooms, belonging to the phyla Ascomycota and Basidiomycota, comprise approximately 14,000 known species, among which a small fraction are toxic. While toxic mushrooms are primarily associated with adverse health effects, recent research highlights their potential as sources of bioactive compounds with promising therapeutic applications.MethodsA systematic review was conducted using four major electronic databases: Web of Science, Google Scholar, PubMed, and ScienceDirect. The literature search, completed on July 1, 2024, utilized keywords including \"Poisonous mushrooms,\" \"Mushroom toxins,\" \"Mycotoxins,\" \"Beta-glucans,\" \"Psilocybin,\" and \"Therapeutic applications.\" Articles were selected based on specific inclusion criteria, focusing on studies investigating the biochemical, toxicological, and pharmacological properties of toxic mushroom compounds. Studies unrelated to mushrooms, non-peer-reviewed sources, or those with outdated or incomplete data were excluded.ResultsThis review examines key toxic mushroom compounds such as amanitins, phallotoxins, ibotenic acid, muscimol, orellanine, and gyromitrin, emphasizing their biosynthesis, structural features, and health effects. Despite their toxicity, compounds like beta-glucans, polysaccharides, lectins, and psilocybin exhibit immune-modulating, anticancer, and neuroprotective properties. These bioactive compounds have shown promise in targeting cancer stem cells and enhancing neurotransmitter activity, positioning them as potential therapeutic agents.DiscussionUnderstanding the therapeutic potential of toxic mushroom-derived bioactive compounds bridges toxicology and pharmacology, offering novel avenues for drug discovery. Comparative analysis with existing treatments highlights their unique advantages in modern medicine.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251323134"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of detergent component sodium dodecyl sulfate on growth hormone secretion in GH3 cells: Implications for pediatric exposure and accidental ingestion.","authors":"Hua Tang, Lanlan Li","doi":"10.1177/09603271251332255","DOIUrl":"10.1177/09603271251332255","url":null,"abstract":"<p><p>IntroductionSodium dodecyl sulfate (SDS), a widely used surfactant in detergents, has raised concerns due to its potential health risks, particularly in children. This study evaluates the impact of SDS exposure on GH secretion in GH3 cells, focusing on oxidative stress as a key mechanism.MethodsGH3 cells were treated with varying concentrations of SDS (0.001-10 mM) for 24 or 48 h. Cell viability was assessed using the MTT assay, while GH secretion was quantified via ELISA. Oxidative stress levels were evaluated through ROS fluorescence assays, and gene expression of Nrf2, IL-6, TNF-α, and caspase-3 was analyzed using qPCR. Additionally, the antioxidant N-acetylcysteine (NAC) was used to determine its protective effects against SDS-induced oxidative stress.ResultsSDS exposure led to a dose-dependent decrease in GH secretion and cell viability, with oxidative stress identified as a primary driver. Nrf2 exhibited a biphasic response, showing transient upregulation at low doses but suppression at higher concentrations, exacerbating oxidative damage. NAC treatment reduced ROS levels and partially restored GH secretion, confirming the role of oxidative stress in SDS-induced toxicity.DiscussionThese findings suggest that SDS exposure may disrupt endocrine function, warranting further risk assessment of its safety in consumer products. Given SDS's prevalence in household products, future research should focus on the long-term effects of SDS exposure to children and potential therapeutic interventions to mitigate oxidative damage.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251332255"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico and in vivo experiments of Huperzine A modulating the development of obstructive sleep apnea by transcriptionally regulating pyruvate carboxylase expression via retinoid X receptor alpha.","authors":"Juan Huang, Hui Li, Qin Huang, Li Wang, Ying Wu, Xin Tan","doi":"10.1177/09603271251342572","DOIUrl":"https://doi.org/10.1177/09603271251342572","url":null,"abstract":"<p><p>IntroductionThis study investigated the molecular mechanism by which HuA influences the expression of pyruvate carboxylase via retinoid X receptor alpha (RXRA), thereby affecting the progression of obstructive sleep apnea (OSA).MethodsBioinformatics analysis including screening of differentially expressed genes (DEGs) and searching the downstream target genes of RXRA were conducted. Cognitive function, neuronal damage, oxidative stress, and inflammation were evaluated in chronic intermittent hypoxia (CIH) mouse models. The Morris water maze test was used to assess swimming path length, escape latency, and platform crossing times. H&E and Nissl staining was performed to evaluate pathological changes and neuronal counts in brain tissue. ELISA was utilized to measure the oxidative stress levels and inflammatory cytokines. RXRA enrichment in the pyruvate carboxylase promoter region in CIH was assessed using Chromatin Immunoprecipitation (ChIP), and the effect of RXRA on pyruvate carboxylase promoter activity was analyzed using dual-luciferase assay.ResultsRXRA was identified as a potential regulatory target gene of HuA. Pyruvate carboxylase was identified as a RXRA target gene and a significant DEG in OSA. CIH-induced cognitive impairment, neuronal damage, oxidative stress, and inflammation in mice, while such symptoms were alleviated by HuA treatment. In OSA, suppression of RXRA expression led to reduced pyruvate carboxylase expression. HuA treatment enhanced RXRA expression, thereby promoting pyruvate carboxylase expression. HuA alleviated CIH-induced cognitive impairment, neuronal damage, oxidative stress, and inflammation via the RXRA/pyruvate carboxylase axis.ConclusionIn summary, HuA alleviates CIH-induced cognitive impairment, neuronal damage, oxidative stress, and inflammation by promoting the RXRA/pyruvate carboxylase axis.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251342572"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cigarette smoking extract induces mitochondrial dysfunction and apoptosis in HUVECs via the Sirt1-SHH axis.","authors":"Weiming Wang, Gang Yuan, Guang Li, Tingting Zhao, Yue Chen, Youhua Xu","doi":"10.1177/09603271251332251","DOIUrl":"10.1177/09603271251332251","url":null,"abstract":"<p><p>IntroductionCigarette smoking extract (CSE) can cause endothelial cell (EC) dysfunction, and then promote the occurrence and development of atherosclerosis. However, the molecular mechanisms underlying CSE-induced EC dysfunction are unknown. Sirt1, as a deacetylase, is involved in various biological processes of ECs. Therefore, this study investigated whether CSE induces apoptosis and mitochondrial dysfunction in human umbilical vein endothelial cells (HUVECs) via Sirt1-dependent mechanisms.MethodsHUVEC activity was assessed using MTT and crystal violet staining following treatment with different concentrations of CSE. Lentiviral transfection technology was used to generate HUVECs overexpressing Sirt1. Apoptosis was detected by Tunnel staining. MitoTracker™ Deep Red FM and JC-1 were used to assess mitochondrial structure and membrane potential. ELISA was used to detect the expression of superoxide dismutase (SOD) and malondialdehyde (MDA). qPCR was used to determine mRNA expression. Atherosclerosis was evaluated by oil red O staining in ApoE-KO mice after cigarette smoke exposure.ResultsCSE decreased Sirt1 and sonic hedgehog (SHH) expression, leading to mitochondrial dysfunction and apoptosis in HUVECs. Overexpressing Sirt1 or activating the SHH signaling pathway attenuated CSE-induced apoptosis and mitochondrial dysfunction. However, inhibiting the SHH signaling axis attenuated the protective effect of Sirt1 overexpression on CSE-induced apoptosis and mitochondrial dysfunction. In vivo studies also showed that cigarette smoke exacerbated atherosclerosis in ApoE-KO mice, downregulating Sirt1, SHH, and Gli1 expression in the aorta. Additionally, cigarette smoke increased Bax expression and decreased Bcl-2 expression in ApoE-KO mice aortas.DiscussionsSmoking can affect all stages of the atherosclerosis process, and the specific mechanism remains unclear. This study confirms that CSE can induce mitochondrial dysfunction and apoptosis of HUVECs by reducing Sirt1 expression and inhibiting SHH signaling activation. These findings provide new insights into the prevention and treatment of smoking-induced atherosclerosis.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251332251"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology and experimental verification: Rosmarinic acid alleviates doxorubicin-induced cardiomyocyte apoptosis by regulating BCL2L1.","authors":"Sicong Xie, Cheng Chang, Rongxing Jiang, Lifeng Wang, Yunli Yang, Zongjin Li, Yang Zhang","doi":"10.1177/09603271251354890","DOIUrl":"https://doi.org/10.1177/09603271251354890","url":null,"abstract":"<p><p>PurposeThis study investigated the mechanism by which Rosmarinic acid (RA) may alleviate doxorubicin (DOX)- induced cardiomyocyte apoptosis.MethodsThe target genes of RA, DOX-related differentially expressed genes, and GEO database related genes were retrieved by bioinformatics analyses. The results of these analyses were further intersected to identify candidate genes. The protein-protein interaction network was constructed to develop the pharmacophore model. The molecular docking was simulated to determine the core target B-cell lymphoma 2-like 1 (BCL2L1) for subsequent molecular mechanism investigation <i>in vitro</i>. The effects of DOX and RA on the apoptosis of H9c2 cells were assessed using the CCK8 assay. The present study investigated the effect of RA on DOX-induced oxidative stress in cardiomyocytes. This investigation was conducted using an ELISA test and a DCFH-DA probe. The JC-1 probe was utilized to assess the effect of RA on DOX-induced cardiomyocyte mitochondrial membrane permeability. A Western blot assay was conducted to ascertain the activation of multiple signaling molecules, including those belonging to the BCL-2 and caspase-3 families, within the apoptosis pathway.ResultsA total of 17 differentially expressed genes (DEGs) were screened, and five genes were selected as hub DEGs. A subsequent KEGG enrichment analysis revealed that these DEGs were significantly enriched in various biological processes and pathways, including the MAPK signaling pathway, autophagy, apoptosis, and the TNF signaling pathway. The pharmacophore model and molecular docking of five candidate targets with RA were successfully established. It is noteworthy that DOX treatment led to a suppression of SOD and GSH levels, an exacerbation of oxidative stress, and a promotion of cardiomyocyte apoptosis. Furthermore, it has been demonstrated to suppress mitochondrial membrane permeability. Subsequent RT-qPCR analysis of the hub genes revealed that only <i>BCL2L1</i> exhibited significant alterations. Treatment with DOX altered the expression levels of apoptosis-associated proteins, BCL-2 family members, and caspase-3 family members. However, the administration of RA mitigated the deleterious effects of DOX on cardiomyocytes.ConclusionsThe protective effects of RA may against myocardial cell apoptosis are likely mediated through its activation of BCL2L1 and inhibition of caspase cascade protein expression in myocardial cells.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251354890"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Re suppresses high glucose-induced apoptosis of placental trophoblasts through endoplasmic reticulum stress-related CHOP/GADD153.","authors":"Guihong Zeng, Weiyang Zou, Changdi Liu, Yulan Chen, Tingmei Wen","doi":"10.1177/09603271241307835","DOIUrl":"10.1177/09603271241307835","url":null,"abstract":"<p><p><b>Background:</b> Gestational diabetes mellitus (GDM) is a metabolic disorder that arises during pregnancy and heightens the risk of placental dysplasia. Ginsenoside Re (Re) may stabilize insulin and glucagon to regulate glucose levels, which may improve diabetes-associated diseases. <b>Purpose:</b> This study aims to investigate the mechanism of Re in high glucose (HG)-induced apoptosis of trophoblasts through endoplasmic reticulum stress (ERS)-related protein CHOP/GADD153. <b>Research Design:</b> Human trophoblast cells HTR-8/SVneo were treated with HG to simulate the HG environment <i>in vitro</i>, while normal glucose (NG) was used as the control. <b>Study Sample:</b> NG (5 mM) or HG (25 mM)-cultured HTR-8/SVneo cells were treated with 10, 20 or 40 μM Re. HG-cultured cells were treated with 5 mM ERS inducer 2-Deoxy-D-glucose (2-DG) and transfected with oe- CHO. <b>Data Collection and/or Analysis:</b> Cell viability and apoptosis were detected by CCK-8 and flow cytometry; LDH release, superoxide dismutase (SOD), malonaldehyde (MDA) and glutathione (GSH) levels were detected using kits; the apoptosisrelated proteins and ERS-related proteins were assessed by western blot. <b>Results:</b> Re (10, 20 or 40 μM) had no significant effect on NG-treated HTR-8/SVneo cell viability. Re (20 or 40 μM) could enhance the viability of HG-treated trophoblasts. Re (40 μM) inhibited apoptosis of HGtreated trophoblasts, ERS and alleviated oxidative stress evidenced by suppressed phosphorylation of PERK, IRE1α, reduced protein expression of ATF6, CHOP/GADD153, and inhibited MDA accumulation, GSH and SOD loss. ERS activation or CHOP/GADD153 overexpression reversed Re's inhibition on HG-induced apoptosis of trophoblasts. <b>Conclusions:</b> Re repressed HG-induced placental trophoblast apoptosis by mediating ERS-related protein CHOP/GADD153.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271241307835"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down-regulation of E2F1 attenuates UVB-induced human lens epithelial cell oxidative stress and pyroptosis through inhibiting NLRP3.","authors":"Fang Wang, Fan Yang, Guiqi Yang, Qi Zhou, Hongbin Lv","doi":"10.1177/09603271241309258","DOIUrl":"https://doi.org/10.1177/09603271241309258","url":null,"abstract":"<p><strong>Background: </strong>It is well-known that ultraviolet B (UVB) causes cataracts by inducing pyroptosis and the production of reactive oxygen species (ROS) in human lens epithelial cells (HLECs). The transcription factor E2F1 (E2F1) serves as a positive regulator of disrupted pathways involved in histone modification and cell cycle regulation. However, its function in UVB-treated HLECs remains unknown.<b>Purpose:</b> This study aims to investigate the function of E2F1 in UVB-treated HLECs, with a particular focus on its interaction with NLRP3 and its impact on oxidative stress and pyroptosis. <b>Research Design:</b> HLECs were irradiated with UVB, and cell damage was assessed using CCK-8, ROS, and pyroptosis detection. The interaction between E2F1 and NLRP3 was confirmed using Chromatin immunoprecipitation (ChIP)-qPCR and dual-luciferase reporter assays.<b>Study Sample:</b> The study was conducted using UVB-treated HLECs.</p><p><strong>Data collection and/or analysis: </strong>Collected data were statistically analyzed using one-way analysis of variance (ANOVA).</p><p><strong>Results: </strong>Our results show that HLECs were much more susceptible to oxidative stress, pyroptosis, and E2F1 in response to UVB-irradiation, but that E2F1 down-regulation effectively counteracted these effects. E2F1 was then suggested as a potential NLRP3 transcription factor by bioinformatics studies. At the same time, luciferase and CHIP assays showed that E2F1 could bind to the NLRP3 promoter and enhance NLRP3 transcription. In addition, the protective effects of si-E2F1 against oxidative stress and pyroptosis in HLECs are counteracted by overexpressing NLRP3.</p><p><strong>Conclusions: </strong>All of the above provided the possibility to demonstrate that E2F1 plays a crucial role in regulating oxidative stress and pyroptosis in UVB-induced HLECs through inhibiting NLRP3, and it promotes oxidative stress-induced pyroptosis by suppressing NLRP3 expression.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271241309258"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conflicts of interest in the International Agency for Research on Cancer process of identifying carcinogenic hazards to humans.","authors":"Susan A Elmore, Colin Berry, Brad Bolon, Gary A Boorman, Alys E Bradley, Samuel M Cohen, James E Klaunig, Felix M Kluxen, Robert R Maronpot, Abraham Nyska, Tracey L Papenfuss, Jerold E Rehg, David B Resnik, Ivonne McM Rietjens, Thomas J Rosol, Andrew W Suttie, Trenton R Schoeb, Christian Strupp, Bob Thoolen, Klaus Weber","doi":"10.1177/09603271241269020","DOIUrl":"10.1177/09603271241269020","url":null,"abstract":"<p><p>Managing conflicts of interest (COIs) in scientific decision-making is important for minimizing bias and fostering public trust in science. Proper management of COIs has added significance when scientists are making decisions that impact public policy, such as assessing substances for carcinogenicity. The International Agency for Research on Cancer (IARC) organizes expert working groups to identify putative carcinogens and determine whether or not the hazard is likely to present significant potential harm to humans. While IARC has policies for managing COIs, prior professional experience with the substance being assessed is not defined as a COI. Indeed, IARC working group members are chosen based on subject matter expertise, including prior publication on the substance under review. However, a person's prior experience with a substance poses a significant potential COI by equipping them with strong pre-existing views about the substance's toxicity and carcinogenicity. To minimize the risk of bias in IARC working groups, participants with voting powers should be independent scientific experts with sufficient professional experience to review carcinogenicity data but with no substantial prior experience with the substance under review. A related IARC practice restricting data review by working groups to selected publications is another significant COI. Instead, all accessible data should be available for consideration by working groups in assessing the carcinogenic hazard of substances. Another recommendation to reduce potential bias would be to reinstate the option of \"probably not carcinogenic to humans\".</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271241269020"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The acute and sub-chronic toxicological effects of 3-amino-9-ethylcarbazole (AEC) on zebrafish.","authors":"Erna Vásárhelyi, Gergely Rácz, Béla Urbányi, Balázs P Szabó, Dóra Szepesi-Bencsik, István Szabó, Illés Bock, Cintia Volner, Jeffrey Daniel Griffitts, Balázs Kriszt, Katalin Bakos, Zsolt Csenki","doi":"10.1177/09603271251318968","DOIUrl":"10.1177/09603271251318968","url":null,"abstract":"<p><strong>Introduction: </strong>In this study, we sought to determine the sub-chronic toxicological effects of AEC on zebrafish embryos.</p><p><strong>Methods: </strong>We utilized fish early life stage (FELS) and fish embryo toxicity (FET) tests, vascular, neurological, and renal transgenic zebrafish lines, and gene expression anal-ysis of the zebrafish tissue.</p><p><strong>Results: </strong>In the FET tests, AEC caused several abnormalities in the larvae, with the LC50 at 24 hpf being 4.076 ± 0.221 mg/L and 3.296 ± 0.127 mg/L at 96 hpf. In the FELS test, AEC was shown to be lethal following 16 days of exposure at 0.5 mg/L, 1 mg/L and 2 mg/L. Some of the transgenic zebrafish lines exhibited slight changes in fluorescent signaling pat-terns after exposure to AEC at 1 mg/L and 2 mg/L. Notable results of the gene expression analysis revealed: gpx4b and got2 were downregulated in the liver; HIF1a was downregulated at 0.25 mg/L and 0.5 mg/L concentrations, NOTCH1a and fli-1 genes were downregulated at all concentrations, and A2b was upregulated in the vasculature; a1T, ngn1, elavl3, syn2a, mbp, gap43 were down-regulated in the nervous system; and wt1b was downregulated in the kidney.</p><p><strong>Discuccion: </strong>Altogether, the results of our study indicate the potential for AEC to cause harm to organisms.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251318968"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-induced autophagy attenuates ferredoxin 1-mediated cuproptosis in colorectal cancer cells.","authors":"Long Qin, ZhenBing Lv, BinYu Luo, Jing Yu, Min Li, Rong Jing, JingDong Li","doi":"10.1177/09603271251335393","DOIUrl":"https://doi.org/10.1177/09603271251335393","url":null,"abstract":"<p><p>IntroductionCuproptosis has emerged as a potential therapeutic target for colorectal cancer (CRC). This study investigated the role of ferredoxin 1 (FDX1) in regulating cuproptosis under hypoxic conditions and explored the impact of autophagy on this process in CRC.MethodsCRC patient samples and cell lines were used in this study. Cells were exposed to hypoxia and treated with Es-Cu (a copper supplement) and rapamycin, an autophagy inducer. FDX1 expression in clinical tissues was assessed in clinical tissues using qPCR and Western blot. The CCK8 assay, EdU staining, and Transwell assay were employed to evaluate the malignant behavior of tumor cells. Copper content and DLAT oligomerization were measured. A nude mouse xenograft model was used to explore the role of FDX1 under hypoxic conditions.ResultsCompared with adjacent normal tissues, elevated FDX1 expression was observed in CRC tissues. <i>In vitro</i>, hypoxia or Es-Cu treatment upregulated FDX1 expression in CRC cell lines, resulting in reduced cell proliferation and increased cellular damage. FDX1 overexpression under hypoxic conditions suppressed migration, invasion, and proliferation while promoting cellular damage and DLAT oligomerization. Rapamycin-induced autophagy reversed the inhibitory effects of FDX1 overexpression on CRC cells. <i>In vivo</i>, rapamycin treatment attenuated the tumor-suppressive effects of FDX1 overexpression in nude mouse xenograft models.DiscussionThis study demonstrated that hypoxia-induced autophagy inhibits FDX1-mediated cuproptosis, leading to resistance to copper-induced cell death in CRC cells. Targeting the autophagy pathway may provide a novel therapeutic strategy to overcome resistance to cuproptosis and improving CRC treatment outcomes.</p>","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251335393"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}