Identification of important genes related to ferroptosis in early missed abortion based on WGCNA

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 3, 2025

Early missed abortion is defined as a pregnancy of ≤ 12 weeks in which there cessation life the developing embryo or fetus, leading to its retention within uterine cavity without being spontaneously expelled promptly. This condition commonly observed and significantly impacts human reproductive health. study aimed identify key genes related ferroptosis that could serve novel biomarkers for early abortion. Findings from gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses indicate correlation between iron- DEFRGS modules p53 signaling, mitophagy-animal, protein digestion absorption pathways. An analysis protein-protein interaction (PPI) network was conducted on DEFRGs, identifying five central (TP53, EZH2, TIMP1, SLC3A2, GABARAPL2) using STRING Cytohubba ROC curves. The expression pivotal both missed-abortion control groups verified by RT-qPCR. CIBERSORT revealed notable increase infiltration levels CD8 + T lymphocytes M2 macrophages among individuals group. Additionally, ceRNA constructed predict interactions mRNA, miRNA, lncRNA genes. However, interacting miRNAs predicted SLC3A2 miRanda, miRDB, TargetScan databases were limited hsa-miR-661 hsa-miR-4311, with no lncRNAs found spongeScan database. research has identified be targeted detection management abortions.

Language: Английский

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An omics review and perspective of researches on intrahepatic cholestasis of pregnancy

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Intrahepatic cholestasis of pregnancy (ICP) is one the common complications that may threaten health both pregnant women and their fetuses. Hence, it vital importance to identify key moleculars associated functional pathways ICP, which will help us better understand pathological mechanisms as well develop precise clinical biomarkers. The emerging developing multiple omics approaches enable comprehensive studies genome, transcriptome, proteome metabolome samples. present review collected summarized based aiming provide an overview current progress, limitations future directions. Briefly, these covered a broad range research contents by comparing different experimental groups including ICP patients, subtypes, fetuses, models other complications. Correspondingly, studied samples contain various types samples,

Language: Английский

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Metformin ameliorates Gestational Diabetes Mellitus via inhibiting ferroptosis of trophoblasts through the Nrf2/HO-1 signaling pathway

Free Radical Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: Feb. 17, 2025

Both mothers and infants experience oxidative stress due to gestational diabetes mellitus (GDM), which is strongly associated with adverse pregnancy outcomes. Ferroptosis, a novel form of programmed cell death characterized by iron-dependent lipid peroxidation, believed play critical role in the pathogenesis progression GDM. Metformin (MET) has shown potential alleviating stress; however, research on its specific mechanisms action GDM remains limited. We collected placental tissues from patients healthy controls established an vitro model. measured markers ferroptosis including malondialdehyde (MDA), glutathione (GSH), peroxidase 4 (GPX4) activity. Additionally, we evaluated reactive oxygen species (ROS) levels, apoptosis, viability, migration Our findings revealed significant changes group compared controls, increased MDA GSSG decreased GSH reduced expression GPX4 protein placenta. High-glucose (HG) conditions were reduce trophoblast viability migration, accompanied elevated ROS as well GSH, GPX4, Nrf2, HO-1 proteins. Importantly, treatment MET reversed these effects, similar deferoxamine mesylate (DFOM), known inhibitor. These results confirm occurrence placentas demonstrate that mitigates high-glucose-induced trophoblasts through Nrf2/HO-1 signaling pathway. This study provides insights into protective MET, offering therapeutic strategies for management.

Language: Английский

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Increased Trophoblast Cell Ferroptosis via HMGB1/ACSL4 Pathway Is Associated with Spontaneous Abortion

Reproductive Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Abstract Introduction Trophoblast cells undergo ferroptosis in pregnancy-related diseases. HMGB1 participates pathological ferroptosis. However, whether lipopolysaccharide (LPS) -mediated expression induces the of trophoblast and further spontaneous abortion (SA) remains unknown. Methods ACSL4 were measured villous tissues from 20 women with SA elective abortion. Human HTR-8/SVneo treated LPS to establish an vitro model. The hallmarks including MDA, GSH, Fe 2+ ROS detected using indicated assay kits. Results levels significantly higher than those normal control group. interacts stabilizes promote cells. Conversely, and/or inhibition attenuated LPS-induced Conclusions An HMGB1/ACSL4 axis is engaged cells, may be targeted design treatments preventing SA.

Language: Английский

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Tiaojing Cuyun Recipe inhibits ferroptosis through SLC7A11/GSH/GPX4 axis to improve endometrial receptivity of mice with embryo implantation dysfunction

Journal of Traditional and Complementary Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Association of Oxidative Stress and Iron Accumulation in Pregnant Women of Indian Origin with a History of Miscarriage: A Case–Control Study

International Journal of Infertility & Fetal Medicine, Journal Year: 2025, Volume and Issue: 15(3), P. 123 - 129

Published: March 27, 2025

Language: Английский

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Ferroptosis contributed to endoplasmic reticulum stress in preterm birth by targeting LHX1 and IRE-1

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111777 - 111777

Published: March 1, 2025

Language: Английский

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Maternal Thrombophilia Disrupts Fetal Redox Homeostasis

Reproductive Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Language: Английский

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The NFE2L2 (NRF2) transcription factor controls genes involved in the oxidative stress response and inflammation in myometrial cells

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 119985 - 119985

Published: May 1, 2025

Language: Английский

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Ferroptosis in chronic obstructive pulmonary disease: From cellular mechanisms to therapeutic applications

Chinese Medical Journal, Journal Year: 2024, Volume and Issue: 137(10), P. 1237 - 1239

Published: April 9, 2024

To the Editor: Chronic obstructive pulmonary disease (COPD) is a global public health challenge without effective treatment currently available, affecting >300 million individuals worldwide. Comprehensively understanding pathogenesis of this required. Recently, ferroptosis, form cell death driven by iron-dependent lipid peroxidation, has been associated with COPD.[1] Multiple signaling pathways, such as glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1), and tetrahydrobiopterin-dependent well iron metabolism, are involved in regulating ferroptosis[2,3] [Figure 1A]. Here, we provide comprehensive overview recent advances role COPD, highlighting potential therapeutic strategies targeting for treating disease.Figure 1: (A) Signaling pathways ferroptosis. (B–D) Ferroptosis BECs (B), macrophages (C), ECs (D) contributes to COPD. (E) Targeting various cells mitigate ACSL4: Acyl-CoA synthetase long-chain family member 4; ALOX15: Arachidonate 15-lipoxygenase; ALOX5: 5-lipoxygenase; BECs: Bronchial epithelial cells; COPD: disease; circSAV1: Circular RNA SAV1; DHFR: Dihydrofolate reductase; ECs: Endothelial FSP1: 1; FTH: Ferritin heavy chain; FTL: light GPX4: Glutathione GSH: Glutathione; GSS: synthetase; GSSG: Oxidized glutathione; GSR: Glutathione-disulfide HMOX-1: Heme oxygenase-1; iNOS: Inducible nitric oxide synthase; IREB2: Iron-responsive element binding 2; LOX: Lipoxygenase; LTB4: Leukotriene B4; MFG-E8: Milk fat globule-EGF factor 8; MMP9: Matrix metalloproteinase 9; MMP12: 12; NCOA4: Nuclear receptor coactivator Nrf2: erythroid 2-related PGE2: Prostaglandin E PLOO•: Lipid peroxyl radicals; PLOOH: Phospholipid hydroperoxides; PRMT7: Arginine methyltransferase 7; PTGS2: synthase PUFAs: Polyunsaturated fatty acids; PUFA-PLs: PUFA containing phospholipids; RAP1A: Ras-related 1A; SIRT3: Sirtuin 3; SLC40A1: Solute carrier 40A1; STEAP3: Six-transmembrane antigen prostate TF: Transferrin; TFRC: Transferrin receptor; TXNRD1: Thioredoxin reductase USP14: Ubiquitin-dpecific protease 14; YTHDF1: YTH N6-methyladenosine 1.Ferroptosis bronchial (BECs) Excessive deposition cigarette smoke (CS)-exposed leads increased ferritin expression. This process activates ferritinophagy mediated nuclear (NCOA4). Notably, knockdown NCOA4 mice reduces CS-induced ferroptosis.[4] In downregulated 2 (Nrf2) expression Nrf2 promoter hypermethylation. Conversely, enhances GPX4 levels, inhibits BECs, mitigates COPD.[5] Moreover, CS extract (CSE)-induced peroxidation sirtuin3 inactivation promoting inducible (iNOS) levels potentially triggering COPD.[6] globule epidermal growth 8 (MFG-E8) identified mitigator CSE-induced ubiquitin specific peptidase 14 (USP14) stabilizes MFG-E8 protein, suppressing ferroptosis.[7] m6A-modified circular SAV1 (circSAV1) forms an RNA–protein complex that promotes translation iron-responsive (IREB2) mRNA. Increased IREB2 disrupt homeostasis, resulting accumulation labile pool contributing cells. circSAV1 reversed suggesting its crucial regulatory process.[8] Overall, COPD 1B]. ferroptosis-sensitive M2-like macrophages.[9] Protein arginine 7 (PRMT7) regulated kappa B (NF-κB)/RelA activation also lung injury severity Pro-inflammatory PRMT7 stimulate arachidonate 5-lipoxygenase leukotriene B4 release, inducing acetyl coenzyme A (acyl-CoA) (ACSL4) rendering them more susceptible COPD.[1,10] M2 matrix (MMP) 9 MMP12 were observed CS-exposed co-cultured CSE-treated BECs.[11] exposure led elevated overload peroxidation-induced may contribute macrophage polarization 1C]. endothelial (ECs) interaction between exacerbating Wang Xia[12] exposed CSE homocysteine, characterized reduced FSP1 ACSL4 suggests disruption microvascular barrier Yu et al[13] discovered normal release exosomes micro (miR)-26a-5p, which can be transported into BECs. Within miR-26a-5p targets prostaglandin-endoperoxide (PTGS2) mRNA, inhibiting These findings suggest beneficial 1D]. Dihydroquercetin Nrf2-mediated inhibit COPD.[14] Curcumin attenuates inflammation BECs.[15] Scutellarein potent inhibitor through chelating Fe2+ reducing intracellular but antiferroptotic effects hindered 15-lipoxygenase overexpression.[16] addition these natural compounds, deferoxamine, ferrostatin-1, liproxstatin-1 BECs.[4,8] Sodium pyruvate GPX4/Nrf2 pathway BECs.[17] Hydrogen sulfide (H2S) peroxisome proliferator-activated receptor-γ NCOA4-mediated autophagy.[18] hydrosulfide (NaHS), H2S donor, Furthermore, gene therapy using lentiviral system (si_ACSL4) showing promise strategy COPD.[12] 1E]. study induce found M1 resistant whereas susceptible.[9] exhibited higher heme oxygenase-1 (HMOX1) than macrophages. Inhibiting HMOX1 zinc protoporphyrin (ZnPP) effectively prevented induced CSE. ZnPP, deferoxamine bronchoalveolar lavage fluid from treatments protected against COPD.[9] exacerbates dyslipidemia, atherosclerotic plaque formation, induces function decline, causes pathological damage, disrupts function, triggers fed high-fat diet. By mitigating preserving Tongxinluo prevent complicated atherosclerosis.[19] highlight approach summary, comprehensively analyze macrophages, treatment. However, several important questions remain addressed. First, future studies should use integrative omics approaches elucidate underlying mechanisms Second, further investigation required understand inhibitors on other types Finally, it determine whether occurs during entire development or mainly manifests advanced stages. Funding work was supported National Natural Science Foundation China (No. 82200084), Sichuan Province 2023NSFSC1456), Postdoctoral funded project TB2023047), Fundamental Research Funds Central Universities, University Interdisciplinary Innovation Fund 0020404153020). Conflicts interest None.

Language: Английский

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