Human & experimental toxicology最新文献_第2页

Down-regulation of E2F1 attenuates UVB-induced human lens epithelial cell oxidative stress and pyroptosis through inhibiting NLRP3. 下调E2F1通过抑制NLRP3减弱uvb诱导的人晶状体上皮细胞氧化应激和焦亡。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271241309258

Fang Wang, Fan Yang, Guiqi Yang, Qi Zhou, Hongbin Lv

{"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":"Background: 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.Purpose: 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. Research Design: 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.Study Sample: The study was conducted using UVB-treated HLECs.Data collection and/or analysis: Collected data were statistically analyzed using one-way analysis of variance (ANOVA).Results: 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.Conclusions: 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.","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}

引用次数: 0

Conflicts of interest in the International Agency for Research on Cancer process of identifying carcinogenic hazards to humans. 国际癌症研究机构在确定对人类的致癌危害过程中的利益冲突。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271241269020

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

{"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":"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\".","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}

引用次数: 0

The acute and sub-chronic toxicological effects of 3-amino-9-ethylcarbazole (AEC) on zebrafish. 3-amino-9-ethylcarbazole (AEC) 对斑马鱼的急性和亚慢性毒理效应。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271251318968

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

{"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":"Introduction: In this study, we sought to determine the sub-chronic toxicological effects of AEC on zebrafish embryos.Methods: 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.Results: 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.Discuccion: Altogether, the results of our study indicate the potential for AEC to cause harm to organisms.","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}

引用次数: 0

Hypoxia-induced autophagy attenuates ferredoxin 1-mediated cuproptosis in colorectal cancer cells. 低氧诱导的自噬可减弱结直肠癌细胞中铁氧还蛋白1介导的铜增生。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-04-28 DOI: 10.1177/09603271251335393

Long Qin, ZhenBing Lv, BinYu Luo, Jing Yu, Min Li, Rong Jing, JingDong Li

{"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":"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. In vitro, 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. In vivo, 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.","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}

引用次数: 0

Protocatechuic acid mitigates 5-fluorouracil-triggered renal and hepatic injury in rats. 原儿茶酸减轻5-氟尿嘧啶引起的大鼠肾和肝损伤。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-04-14 DOI: 10.1177/09603271251332914

Alhomedy M Alharbi, Hoda E Kafl, Rania R Abdelaziz, Ghada M Suddek

{"title":"Protocatechuic acid mitigates 5-fluorouracil-triggered renal and hepatic injury in rats.","authors":"Alhomedy M Alharbi, Hoda E Kafl, Rania R Abdelaziz, Ghada M Suddek","doi":"10.1177/09603271251332914","DOIUrl":"https://doi.org/10.1177/09603271251332914","url":null,"abstract":"IntroductionNephrotoxicity and hepatotoxicity are substantial side effects triggered in individuals injected with 5-fluorouracil (5-FU), an anticancer drug. This study aimed to investigate the impact of the natural antioxidant and anti-inflammatory phenolic compound; protocatechuic acid (PCA) on 5-FU-provoked renal and hepatic injury in rats.MethodsRats were allocated to 4 groups: control, 5-FU, 5-FU + PCA (50 mg/kg), and 5-FU + PCA (100 mg/kg). Rats were intraperitoneally injected 5-FU (75 mg/kg; once a week for 21 days. Protocatechuic acid (50 and 100 mg/kg/day; orally) was administered for 3 weeks.ResultsRats co-treated with PCA had lower serum kidney and liver function markers than those receiving 5-FU alone. Furthermore, co-treatment with PCA successfully modulated kidney and liver contents of TNF-α, NF-κB p65, active caspase-1, IL-1β, p-p38 MAPK, SOD, GSH, Nrf-2, HO-1 and MDA. Moreover, PCA improved histopathological alterations of both kidney and liver tissues.ConclusionPCA exerts its hepatoprotective and nephroprotective effects against 5-FU-triggered toxicity through modulation of oxidative stress and inflammatory pathways, particularly via Nrf-2 activation and NF-κB inhibition.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251332914"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034989","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}

引用次数: 0

Mechanism of triiodothyronine alleviating acute alcoholic liver injury and delaying alcoholic liver fibrosis progression. 三碘甲状腺原氨酸减轻急性酒精性肝损伤和延缓酒精性肝纤维化进展的机制。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-04-02 DOI: 10.1177/09603271251332505

Renli Luo, Sanqiang Li, Mengli Yang, Junfei Wu, Jiayang Feng, Yue Sun, Yadi Zhao, Longfei Mao

{"title":"Mechanism of triiodothyronine alleviating acute alcoholic liver injury and delaying alcoholic liver fibrosis progression.","authors":"Renli Luo, Sanqiang Li, Mengli Yang, Junfei Wu, Jiayang Feng, Yue Sun, Yadi Zhao, Longfei Mao","doi":"10.1177/09603271251332505","DOIUrl":"10.1177/09603271251332505","url":null,"abstract":"IntroductionAlcoholic liver disease poses a severe threat to human health. The thyroid hormone Triiodothyronine (T3) is closely related to liver metabolism. This study investigated the effect and mechanism of T3 in alcoholic liver injury.MethodsAcute alcoholic liver injury model was established in mice by alcohol administration. Alcoholic liver fibrosis models were established in vivo and in vitro using hepatic stellate cells (HSC)-T6 cells and mice. The role and regulatory mechanism of T3 in the occurrence and progression of alcoholic acute liver injury and fibrosis were analyzed by evaluating key factors involved in cell proliferation and apoptosis, inflammatory response, oxidative stress, and autophagy using histopathological staining.ResultsThe results showed that T3 at low and medium concentrations reduced inflammation and oxidative damage in acute alcoholic liver injury and inhibited HSC activation and delayed the onset and progression of alcoholic liver fibrosis in mice. T3 inhibited the PI3K/AKT and NF-κB signal pathway, increased Nrf2 expression levels, and restored liver autophagy. However, high T3 concentrations had the opposite effect.DiscussionOptimal T3 concentrations protects the liver from alcoholic liver injury by inhibiting inflammatory response and oxidative stress injury and by restoring hepatocyte proliferation, apoptosis, and autophagy.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251332505"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766265","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}

引用次数: 0

Pedunculoside inhibits cardiomyocyte inflammatory biomarkers via Nrf2/HO-1 pathway in high glucose-induced H9c2 cells and diabetic cardiomyopathy model rats. 在高糖诱导的H9c2细胞和糖尿病性心肌病模型大鼠中，足跖草苷通过Nrf2/HO-1途径抑制心肌细胞炎症生物标志物。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI: 10.1177/09603271251322186

Yuanben Lu, Jianqiang Meng, Dewen Zhu, Zhenhua Jiang, Hailiang Ma

{"title":"Pedunculoside inhibits cardiomyocyte inflammatory biomarkers via Nrf2/HO-1 pathway in high glucose-induced H9c2 cells and diabetic cardiomyopathy model rats.","authors":"Yuanben Lu, Jianqiang Meng, Dewen Zhu, Zhenhua Jiang, Hailiang Ma","doi":"10.1177/09603271251322186","DOIUrl":"10.1177/09603271251322186","url":null,"abstract":"IntroductionDiabetic cardiomyopathy (DCM) is a complication of diabetes mellitus (DM) that can lead to heart failure and increase the risk of mortality. Pedunculoside (PE), a novel triterpenoid saponin, exhibits anti-inflammatory and anti-oxidative stress (OS) properties. However, its role in DCM remains unexplored.MethodsDCM models were established and treated with PE or the Nrf2 inhibitor (ML385). In vitro, cell function was evaluated using CCK-8, flow cytometry, qRT-PCR, and ELISA. In vivo, fasting blood glucose and insulin levels in rats were measured. The effects of PE on DCM were assessed using HE staining, TUNEL staining, and corresponding kits. Additionally, Nrf2/HO-1 pathway proteins were analyzed by western blot.ResultsLow doses of PE (2.5, 5, 10, and 20 μM) did not affect the viability of H9c2 cells. PE (10 and 20 μM) improved cell viability and prevented apoptosis, inflammation, and OS in high glucose (HG)-stimulated H9c2 cells. PE also upregulated Nrf2 in the nucleus and enhanced HO-1 and NQO1 expression in HG-treated H9c2 cells. Furthermore, the Nrf2 inhibitor (ML385) reversed PE's protective effects on HG-induced cell injury. In vivo, PE reduced blood glucose, increased insulin, alleviated myocardial injury, inhibited apoptosis, decreased levels of inflammatory factors and OS, and upregulated Nrf2, HO-1, and NQO1 in DCM model rats.DiscussionPE alleviates DCM injury by activating the Nrf2/HO-1 pathway. These findings support the potential therapeutic application of PE in DCM.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251322186"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606777","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}

引用次数: 0

Rhynchophylline promotes microglia phenotypic transformation and repair of cerebral ischaemic injury through the JAK2/STAT3 pathway. 黄连素通过 JAK2/STAT3 通路促进小胶质细胞表型转化和脑缺血损伤的修复。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271251324582

Peng Bai, Caixia Li, Luwei Yin, Yao Li, Meng Ju, Laicang Wang

{"title":"Rhynchophylline promotes microglia phenotypic transformation and repair of cerebral ischaemic injury through the JAK2/STAT3 pathway.","authors":"Peng Bai, Caixia Li, Luwei Yin, Yao Li, Meng Ju, Laicang Wang","doi":"10.1177/09603271251324582","DOIUrl":"10.1177/09603271251324582","url":null,"abstract":"Background: Rhynchophylline (RIN) is an alkaloid known for its ability to effectively block signal transduction related to various neurodegenerative diseases. However, the specific mechanism by which RIN regulates microglial activation and cerebral ischemia remains unexplored. This study aims to investigate the function and molecular pathways through which RIN activates the JAK2/STAT3 signaling cascade, promoting the transformation of microglial phenotypes that contribute to recovery from cerebral ischemic injury.Methods: By establishing a microglia oxygen glucose deprivation/reoxygenation (OGD/R) model and a middle cerebral artery occlusion animal model, we assessed changes in the expression of phenotype-specific marker factors for M1 and M2 microglia, as well as key proteins in the JAK2/STAT3 pathway, utilizing ELISA and Western blot techniques. Histological examination, including HE staining, TUNEL assay, and immunofluorescence, was employed to evaluate pathological changes in brain tissue, along with cell apoptosis and proliferation.Results: The results indicated that microglial activity was significantly reduced and shifted towards the M1 phenotype following OGD/R. However, RIN treatment reversed these changes. When JAK2/STAT3 inhibitors were combined with RIN, it inhibited RIN's protective effect. Animal studies have shown that RIN reduces histopathological changes associated with cerebral ischemia. Additionally, RIN inhibited microglial proliferation in ischemic cortical tissue and increased the expression of M2-type marker proteins, as well as the levels of phosphorylated JAK2 and STAT3 in the ischemic tissue.Conclusion: In conclusion, this study indicates that RIN may protect against cerebral ischemic injury by activating the JAK2/STAT3 pathway, which promotes the transition of microglia to the M2 phenotypic.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251324582"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525592","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}

引用次数: 0

KLF9 mediates NLRP3 inflammasome and reactive oxygen species to mediate pyroptosis in trophoblasts. KLF9介导NLRP3炎性体和活性氧介导滋养细胞焦亡。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI: 10.1177/09603271251324702

Qian Li, Min Chen

{"title":"KLF9 mediates NLRP3 inflammasome and reactive oxygen species to mediate pyroptosis in trophoblasts.","authors":"Qian Li, Min Chen","doi":"10.1177/09603271251324702","DOIUrl":"10.1177/09603271251324702","url":null,"abstract":"IntroductionThe objective of this study was to explore the effect of KLF9 on oxidative stress (OS) and NLRP3-mediated inflammation in preeclampsia (PE).MethodsLipopolysaccharide (LPS)+adenosine triphosphate (ATP)-induced HTR-8/SVneo cells were used as an in vitro PE inflammation cell model. shRNA was used to interfere with KLF9 expression (sh-KLF9) to assess the transfection efficiency and the effect of KLF9 on cell proliferation, migration, and invasion. ELISA was performed to detect OS-related factors and inflammatory cytokines. Reactive oxygen species (ROS) levels and pyroptosis were analyzed using DCFH-DA and TUNEL staining. LPS and ATP induced HTR-8/SVneo cells were co-transfected with sh-PRDX6/sh-KLF9 to explore the potential regulatory effect of KLF9 on PRDX6.ResultsLPS+ATP stimulation increased KLF9 expression in the PE cell model. Specifically, reducing KLF9 levels alleviated morphological damage and enhanced proliferation, migration, and invasion in the in vitro PE cell models. Moreover, inhibiting KLF9 expression decreased protein expression of NLRP3, GSDMD-N, cleaved caspase-1, and cleaved-IL-1β, suppressing cell death in LPS+ATP-induced HTR-8/SVneo cells. Analysis of OS indicators revealed that downregulating KLF9 expression restrained intracellular ROS production, decreased MDA expression, and increased SOD and CAT levels. KLF9 regulated the transcription of PRDX6 to attenuate OS and pyroptosis. Knockdown of PRDX6 partially abolished the effect of KLF9 downregulation on OS and pyroptosis of LPS+ATP-induced HTR-8/SVneo cells, as evidenced by the inhibition of cell proliferation, migration, and invasion, as well as the enhanced activity of the NLRP3 inflammasome.ConclusionDownregulation of KLF9 enhances trophoblast cell invasion and reduces OS and NLRP3 inflammasome activation-mediated pyroptosis.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251324702"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606773","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}

引用次数: 0

Neuroinflammatory chemokine networks in transgenic models of Alzheimer's disease: A comparative multi-compartmental analysis. 阿尔茨海默病转基因模型中的神经炎症趋化因子网络：一项比较多室分析。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-06-05 DOI: 10.1177/09603271251348723

Yangyan Sun, Xinhua Xie, Xiaoqin Zou, Futao Zhou

{"title":"Neuroinflammatory chemokine networks in transgenic models of Alzheimer's disease: A comparative multi-compartmental analysis.","authors":"Yangyan Sun, Xinhua Xie, Xiaoqin Zou, Futao Zhou","doi":"10.1177/09603271251348723","DOIUrl":"https://doi.org/10.1177/09603271251348723","url":null,"abstract":"BackgroundAlzheimer's disease (AD) progression is critically modulated by neuroinflammatory cascades involving chemokine-mediated glial activation.ObjectiveThis study aimed to systematically compare compartment-specific chemokine signatures between two distinct AD mouse models (2×Tg-AD [APPswe/PS1dE9] and 3×Tg-AD [APPswe/PS1M146V/TauP301L]), hypothesizing that differential chemokine expression patterns would emerge in a model- and brain region-specific manner, correlating with glial activation profiles.ResultsUsing a Luminex liquid suspension chip assay, we quantified 22 chemokines in serum and brain tissues from transgenic and non-transgenic controls, complemented by Western blot analysis of microglial and astrocytic markers. Twenty-two chemokines were quantitatively analyzed with three key findings: First, serum analysis revealed elevated levels of (i) CCL11, CCL17, CCL24, CCL27, and CXCL12 in 3×Tg-AD versus non-Tg mice; (ii) CCL22 in 2×Tg-AD versus non-Tg mice; and (iii) CCL5, CCL11, CCL17, CCL24, CCL27, and CXCL12 in 3×Tg-AD versus 2×Tg-AD mice. Second, hippocampal changes showed upregulation of CCL3/CCL12 in 2×Tg-AD and CXCL16 in 3×Tg-AD mice, with cortical alterations demonstrating distinct CCL3/CCL12/CCL4 increases in 2×Tg-AD versus elevated CCL1/CXCL13 in 3×Tg-AD mice. Third, Western blot confirmed enhanced hippocampal microglial activation specifically in 3×Tg-AD mice. ConclusionOur findings establish model-specific chemokine signatures that differentially engage neuroinflammatory pathways, suggesting that 3×Tg-AD mice may better replicate human AD's complex chemokine-glia interactions. This compartmentalized profiling provides a framework for targeting chemokine networks in model-specific therapeutic development and biomarker discovery. Further studies are needed to determine whether elevated chemokine expression directly contributes to microglial activation.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251348723"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236286","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}

引用次数: 0