Polystyrene Nanoplastics Activate Autophagy and Suppress Trophoblast Cell Migration/Invasion and Migrasome Formation to Induce Miscarriage

ACS Nano, Journal Year: 2024, Volume and Issue: 18(4), P. 3733 - 3751

Published: Jan. 22, 2024

Nanoplastics (NPs), as emerging pollutants, have attracted global attention. Nevertheless, the adverse effects of NPs on female reproductive health, especially unexplained miscarriage, are poorly understood. Defects trophoblast cell migration and invasion associated with miscarriage. Migrasomes were identified cellular organelles largely unidentified functions. Whether might affect migration, invasion, migrasome formation induce miscarriage has been completely unexplored. In this study, we selected polystyrene nanoplastics (PS-NPs, 50 nm) a model plastic particles treated human cells pregnant mice PS-NPs at doses near actual environmental exposure in humans. We found that to induced mouse suppressed ROCK1-mediated migration/invasion formation. SOX2 was transcription factor ROCK1. activated autophagy promoted degradation SOX2, thus suppressing SOX2-mediated ROCK1 transcription. Supplementing murine or could efficiently rescue alleviate Analysis protein levels ROCK1, TSPAN4, NDST1, P62, LC-3BII/I PS-NP-exposed cells, villous tissues patients, placental gave consistent results. Collectively, study revealed toxicity their potential regulatory mechanism, indicating NP is risk for health.

Language: Английский

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Hypoxia causes trophoblast cell ferroptosis to induce miscarriage through lnc-HZ06/HIF1α-SUMO/NCOA4 axis

Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103073 - 103073

Published: Feb. 2, 2024

Defects of human trophoblast cells may induce miscarriage (abnormal early embryo loss), which is generally regulated by lncRNAs. Ferroptosis a newly identified iron-dependent programmed cell death. Hypoxia an important and unavoidable feature in mammalian cells. However, whether hypoxia might ferroptosis then miscarriage, as well lncRNA, was completely unknown. In this work, we discovered at the first time that could result miscarriage. We also novel lncRNA (lnc-HZ06) simultaneously (indicated HIF1α protein), ferroptosis, mechanism, HIF1α-SUMO, instead itself, primarily acted transcription factor to promote NCOA4 (ferroptosis indicator) hypoxic Lnc-HZ06 promoted SUMOylation suppressing SENP1-mediated deSUMOylation. HIF1α-SUMO lnc-HZ06 transcription. Thus, both formed positive auto-regulatory feedback loop. This loop up-regulated cells, RM villous tissues, placental tissues hypoxia-treated mice, further induced up-regulating HIF1α-SUMO-mediated Furthermore, knockdown either murine lnc-hz06 or Ncoa4 efficiently suppress alleviate mouse model. Taken together, study provided new insights understanding regulatory roles lnc-HZ06/HIF1α-SUMO/NCOA4 axis among hypoxia, offered effective approach for treatment against

Language: Английский

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BaP/BPDE suppressed endothelial cell angiogenesis to induce miscarriage by promoting MARCHF1/GPX4-mediated ferroptosis

Environment International, Journal Year: 2023, Volume and Issue: 180, P. 108237 - 108237

Published: Sept. 28, 2023

Environmental benzo(a)pyrene (BaP) and its ultimate metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) are universal inevitable persistent organic pollutants endocrine disrupting chemicals. Angiogenesis in placental decidua plays a pivotal role healthy pregnancy. Ferroptosis is newly identified iron-dependent cell death mode. However, till now, BaP/BPDE exposure, ferroptosis, defective angiogenesis, miscarriage have never been correlated; their regulatory mechanisms rarely explored. In this study, we used assays with BPDE-exposed HUVECs (human umbilical vein endothelial cells), decidual tissues serum samples collected from unexplained recurrent matched control groups, of BaP-exposed mouse model. We found that exposure caused ferroptosis then directly suppressed angiogenesis eventually induced miscarriage. mechanism, up-regulated free Fe2+ level promoted lipid peroxidation also MARCHF1 (a novel E3 ligase GPX4) to promote the ubiquitination degradation GPX4, both which resulted HUVEC ferroptosis. Furthermore, GPX4 protein down-regulated levels VEGFA ANG-1, two key proteins function for thus angiogenesis. turn, supplement could suppress recover alleviate Moreover, might predict risk Overall, study uncovered crosstalk among miscarriage, discovering toxicological effects on human reproductive health. This warned public avoid polycyclic aromatic hydrocarbons during pregnancy effectively prevent adverse outcomes.

Language: Английский

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Z-DNA binding protein 1 orchestrates innate immunity and inflammatory cell death

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: 77, P. 15 - 29

Published: March 26, 2024

Language: Английский

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The Emerging Role of m6A and Programmed Cell Death in Cardiovascular Diseases

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 247 - 247

Published: Feb. 8, 2025

N6-methyladenosine (m6A) is the most prevalent internal chemical modification in eukaryotic messenger RNA (mRNA), significantly impacting its lifecycle through dynamic and reversible processes involving methyltransferase, demethylase, binding proteins. These regulate mRNA stability, splicing, nuclear export, translation, degradation. Programmed cell death (PCD), a tightly controlled process encompassing apoptosis, pyroptosis, ferroptosis, autophagy, necroptosis, plays crucial role maintaining cellular homeostasis, tissue development, function. Recently, m6A has emerged as significant research area due to regulating PCD implications cardiovascular diseases (CVDs). In this review, we delve into intricate relationship between various types modification, emphasizing their pivotal roles initiation progression of CVDs such myocardial ischemia-reperfusion (I/R), atherosclerosis (AS), pulmonary hypertension (PH), cardiomyopathy, doxorubicin (Dox)-induced cardiotoxicity (DIC), heart failure (HF), infarction (MI). Our findings underscore potential elucidating CVD pave new pathways for prevention treatment strategies.

Language: Английский

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Defective Homologous Recombination Repair By Up‐Regulating Lnc‐HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 29, 2024

Abstract Human trophoblast cells are crucial for healthy pregnancy. However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in may induce miscarriage is completely unknown. Moreover, abundance BRCA1 (a protein HR repair), its recruitment to DSB foci, and epigenetic regulatory mechanisms, also fully unexplored. In this work, it identified that a novel lnc‐HZ10, which highly experssed villous tissues recurrent (RM) vs their control group, suppresses cell. Lnc‐HZ10 AhR (aryl hydrocarbon receptor) form positive feedback loop. acts as transcription factor promote lnc‐HZ10 transcription. Meanwhile, increases levels by suppressing CUL4B‐mediated ubiquitination degradation. Subsequently, transcription; (mainly 1‐447 nt) interacts with γ‐H2AX; thus, impairs interactions BRCA1. BPDE exposure trigger loop suppress cells, possibly inducing miscarriage. Knockdown murine Ahr efficiently recovers placental alleviates mouse model. Therefore, suggested AhR/lnc‐HZ10/BRCA1 axis be promising target alleviation unexplained

Language: Английский

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Z-nucleic acid sensor ZBP1 in sterile inflammation

Clinical Immunology, Journal Year: 2024, Volume and Issue: 261, P. 109938 - 109938

Published: Feb. 11, 2024

Language: Английский

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BPDE induces ferroptosis in hippocampal neurons through ACSL3 suppression

NeuroToxicology, Journal Year: 2025, Volume and Issue: 107, P. 11 - 21

Published: Jan. 16, 2025

Language: Английский

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Epigenetic regulation in female reproduction: the impact of m6A on maternal-fetal health

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 4, 2025

Language: Английский

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Inhibition of N6-methyladenosine methylation of ASC by berberine ameliorates pyroptosis of renal tubular epithelial cells in acute kidney injury

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111732 - 111732

Published: March 1, 2025

Acute kidney injury (AKI) lacks a definitive therapeutic approach beyond supportive care. One significant pathological mechanism involves the regulated death of tubular epithelial cells; however, regulatory mechanisms underlying this cell pathway require further investigation. The N6-methyladenosine (m6A) modification, recognized as most prevalent modification in eukaryotes, plays critical role processes associated with AKI. Here, study investigates association between methyltransferase-like 3 (METTL3) and pyroptosis mice folic acid (FA)-induced Both vitro vivo experiments have confirmed that METTL3 AKI progression, correlating renal inflammation. Moreover, RNA immunoprecipitation quantitative PCR (RIP-qPCR) analysis demonstrated METTL3-mediated m6A methylation occurred mRNA Apoptosis-associated speck-like protein containing CARD (ASC) H2O2-induced (TCMK-1) cells. Notably, knockdown resulted reduced ASC expression, decreased release inflammatory factors, pyroptosis. In addition, we verified inhibitory effect berberine hydrochloride, monomer used traditional Chinese medicine, on expression. We also ameliorated FA-induced TCMK-1 cells by inhibiting modulating ASC/caspase-1/Gasdermin D axis. These findings provide insights into targeted therapies drug development for

Language: Английский

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