Frontiers in Neurology
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2025
·
IF 2.8
Yuzhu Wu,Xinwang Chen,Feixiang Liu,Yanchen Feng,Ziyun Liao,Xinyu Bu,Wen Fu,Jing Gao,Lihua Wu,Linyuan Fan,Qian Yang,Penglin Yue,Mengyu Wang
Early-life chronic sleep deprivation (CSD) represents a significant risk factor for the development of adult depressive-like behaviors, although the precise molecular mechanisms underlying this association remain incompletely elucidated. In this study, we established a CSD rat model using a rodent sleep deprivation apparatus and employed behavioral tests to assess the effects of early electroacupuncture intervention on adult depressive-like behaviors. The underlying molecular mechanisms were systematically investigated through integrated experimental approaches including Prussian blue staining, transmission electron microscopy, enzyme-linked immunosorbent assay, and Western blot analysis. The experimental results demonstrated that the CSD group rats exhibited significant depressive-like behaviors, accompanied by pathological alterations such as increased iron deposition in hippocampal tissues and structural damage to neuronal mitochondria. Electroacupuncture intervention facilitated hippocampal neuronal repair and remodeling through multiple mechanisms, including the regulation of iron metabolism homeostasis, enhancement of antioxidant capacity, inhibition of ferroptosis, and suppression of excessive autophagy, thereby reversing the CSD-induced depressive-like behaviors. This study provides novel therapeutic strategies and mechanistic insights for the prevention and treatment of adult-onset depression induced by early-life chronic sleep deprivation.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
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IF 6.7
Wei Ye,Lei Wang,Ye Fan,Li Ma,Zaohong Chen,Jinmeng Zhang,Rong Zeng,Xiang Liu
Metabolic dysfunction-associated steatotic liver disease (MASLD) progression closely involves ferroptosis. Using high-fat diet-challenged mice and free fatty acid (FFA)-treated HepG2 cells, we demonstrate that oleanolic acid (OA) ameliorates MASLD and suppresses ferroptosis─an effect validated by the ferroptosis activator Erastin. Supported by network pharmacology, mechanistic analyses reveal that OA exerts synergistic efficacy via a dual-axis network. First, molecular docking, cellular thermal shift assay (CETSA), and molecular dynamics (MD) simulations confirm that OA directly binds PTGS2, mitigating lipid peroxidation and inflammatory mediator release. Second, OA activates the AMPK/ACC metabolic signaling pathway, inhibiting ACC through phosphorylation to correct lipid metabolism disorders, and its antiferroptotic effect can be blocked by AMPK inhibitors. This study first elucidates OA’s therapeutic mechanism against MASLD via “metabolic correction + oxidative inhibition,” outlining a novel strategy for targeting hepatic ferroptosis.
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Journal of Traditional Chinese Medicine
·
2026
·Vol. 46
·期 3
·594
·
IF 2.6
Feng HAO,Jiajia SANG,Chuanyu PENG,Jun HU,Zijian WU,Ling HU,Yihuang GU
OBJECTIVE: To investigate the effects of moxibustion at Zusanli (ST36) on ferroptosis-related proteins in synovial inflammation of rats with rheumatoid arthritis (RA) and verify the mechanism by cell experiments. METHODS: A RA rat model was established using a "disease-syndrome integration" modeling method. The rats were randomly divided into a blank control group (Control group) and a model replication group. Rats with successfully replicated RA models were further divided into a model control group (RA group) and a moxibustion treatment group (RA + Mox group). After intervention, the rats' ankle swelling degree and small animal ultrasound examination were conducted and synovial tissue was examined for pathology, lipid reactive oxygen species (ROS) detection, ferrous ion Fe 2+ double staining, and immunohistochemistry analysis. Serum from three groups of rats were extracted and used for cellular assays, cell counting kit-8 and Western blot validation. RESULTS: (a) Compared to Control group rats, RA rats showed significantly increased footpad swelling ( P < 0.01) and joint inflammation levels ( P < 0.001); compared to RA group, the RA + Mox rats showed significantly decreased footpad swelling ( P < 0.05) and joint inflammation levels ( P < 0.01). (b) There was no difference in lipid ROS levels in the synovial tissue of RA rats compared to Control group rats ( P > 0.05), but the lipid ROS levels in the synovial tissue of RA + Mox rats were significantly increased ( P < 0.01). Compared to Control group rats, RA rats had significantly lower Fe 2+ levels ( P < 0.05); compared to RA rats, the Fe 2+ levels in RA+Mox rats were significantly increased ( P < 0.01). There was no significant difference in beclin 1(BECN1) expression in the synovial tissue of RA rats compared to Control group rats ( P > 0.05), but BECN1 expression in the synovial tissue of RA + Mox rats was significantly increased ( P < 0.01) compared to RA rats. Compared to Control group rats, RA rats had significantly higher Solute Carrier Family 7 Member 11 Gene (SLC7A11) levels in synovial tissue ( P < 0.05); compared to RA rats, the SLC7A11 levels in RA + Mox rats were significantly decreased ( P < 0.05). (c) In the lipopolysaccharides (10 ng/mL) model, 50% concentration of RA rats serum promoted human RA fibroblast-like synovial cell line (MH7A) proliferation (48 h) ( P < 0.05) and 50% concentration of RA + Mox rat serum inhibited MH7A proliferation (48, 72 h) ( P < 0.001). Both 25% and 50% concentrations of RA + Mox rat serum upregulated BECN1 and downregulated SLC7A11 expression in MH7A. CONCLUSION: Moxibustion at Zusanli (ST36) suggests a potential to relieve footpad swelling and synovial inflammation in RA rats, alleviate synovial tissue hyperplasia and thickening. It may induce lipid ROS accumulation in synovial tissue, upregulating Fe 2+ levels, upregulating BECN1 expression, and downregulating SLC7A11 expression in RA rats. Moreover, 50% concentration of rat serum after moxibustion inhibited the proliferation of synovial fibroblasts and regulated the expression of ferroptosis-related proteins.
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Journal of Integrative Medicine-JIM
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2024
·
IF 4.2
Zhen Wang,Min Liu,Guang-xing Li,Liu Zhang,Kai-yue Ding,Si-qi Li,Bing-qing Gao,Peng Cheng,Hyok-Chol Choe,Lun-yue Xia,Yu-tong Yang,Yi Liu,Xue Sui,Jun-nan Ma,Lin Zhang
Objective Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. Methods A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. Results The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. Conclusions SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients.
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Chemical Biology & Drug Design
·
2025
·Vol. 105
·期 5
·e70113
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IF 3.3
Ming Tong,Meng Liu,Liang Chen,Yi-he Lin,Qing Zheng
Liver fibrosis is pathologically associated with ferroptosis. Osthole (OST) has good therapeutic effects on liver fibrosis. Our study sought to investigate the pharmacological effects of OST on ferroptosis in hepatic stellate cells (HSCs) during the development of liver fibrosis and define the mechanisms involved. The in vivo model of liver fibrosis was established by CCl 4 treatment. MTT and EDU assays were used to assess cell viability and proliferation, respectively. The interaction between myocyte enhancer factor 2A (MEF2A) and Y-box binding protein 1 (YBX1) was analyzed by dual luciferase reporter and chromatin immunoprecipitation (ChIP) assays. OST treatment alleviated CCl 4 -induced liver fibrosis in mice by activating ferroptosis. OST induced ferroptosis in HSCs and inhibited the activation of HSCs in vitro, while these effects of OST were reversed by MEF2A overexpression or YBX1 overexpression. Mechanistically, MEF2A activated the Wnt/β-catenin signaling by transcriptionally facilitating YBX1 expression. As expected, the inactivation of Wnt/β-catenin signaling or YBX1 knockdown could reverse the regulatory effect of MEF2A upregulation on the activation of HSCs and ferroptosis in OST-treated HSCs. OST mitigated liver fibrosis by inducing ferroptosis in HSCs and repressing the activation of HSCs through inhibiting the MEF2A/YBX1/Wnt/β-catenin axis.
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Bioengineered
·
2021
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IF 3.269
Shujun Xu,Bingxin Wu,Biying Zhong,Luoqi Lin,Yining Ding,Xiao Jin,Zhiwei Huang,Miaoyang Lin,Huanlin Wu,Danping Xu
Ferroptosis is an important form of myocardial cell death in myocardial ischemia-reperfusion injury (MIRI). Naringenin (NAR), as a flavonoid, has a significant advantage in improving MIRI. But the regulatory effect and mechanism of NAR on ferroptosis in MIRI have not been reported. After the rats were given NAR and induced to form myocardial ischemia-reperfusion (MI/R) injury, Tetrazolium chloride (TTC) staining was used to detect the myocardial infarction area of rats, and Hematoxylin-eosin (H&E) staining was used to detect myocardial injury. The markers of tissue inflammation were detected by ELISA. Serum creatine kinase Serum creatin kinase (CPK), Lactate dehydrogenase (LDH), and lipid peroxide (LPO) and oxidative stress related levels were measured. In addition, iron detection kits were used to detect total iron and Fe2+ levels in cardiac tissues, and western blot was used to detect the expression of ferroptosis-related proteins and the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4). At the cellular level, H9C2 cardiomyocytes were induced by hypoxia/reoxygenation (H/R), and ferroptosis inducer Erastin was administered to detect cell viability, ferroptosis-related indicators, oxidative stress related indicators, and expressions of Nrf2 and GPX4, to explore the mechanisms involved. NAR alleviated MI/R-induced pathological damage, inflammation and lipid peroxidation in myocardial tissue of rats. NAR adjusted the NRF2 /System xc – /GPX4 axis and improved ferroptosis. At the cellular level, ferroptosis inducer Erastin reversed the protective effect of NAR on H/R-induced H9C2 cardiomyocytes. In conclusion, NAR can alleviate MIRI by regulating the Nrf2/System xc-/GPX4 axis to inhibit ferroptosis.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2026
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IF 5.2
Yunpeng Li,Fengzhen Cui,Huanwen Tang
Evaluating endocrine-disrupting chemicals (EDCs) risk such as mono-butyl phthalate (MBP) and bisphenol A (BPA) raises a pressing question: can doses deemed safe for each individual exposure become hazardous in combination? This study aimed to determine whether environmentally relevant concentrations of MBP and BPA exert synergistic neurotoxicity and to elucidate the underlying molecular mechanisms using an integrated multi-omics approach. Exposure concentrations (20 nM each) were derived from epidemiological biomonitoring data. Primary neural stem cells (NSCs) were used to detect CCK-8, reactive oxygen species (ROS), and apoptosis Synergy was evaluated using the Bliss independence model and two-way ANOVA. Transcriptomic (RNA-seq) and untargeted metabolomic (LC–MS) profiling were performed, followed by integrative pathway analysis. Three-dimensional (3D) brain organoids were used to validate the main findings. Co-exposure to MBP and BPA at equimolar concentrations synergistically reduced cell proliferation (BlissΔ >0, E _Observed = 0.371 vs. E _Bliss = 0.163) and synergistically elevated intracellular ROS (interaction index = 2.21, p = 0.0066; two-way ANOVA interaction p = 0.033). Transcriptomic and metabolomic analyses converged on glutathione metabolism as the most significantly dysregulated pathway in the co-exposure group. Integrated multi-omics analysis revealed ferroptosis may serve as the primary mode of synergistic cell death. Three-dimensional brain organoids confirmed the ferroptosis signature, with significantly decreased GPX4 and SLC7A11 protein expression and concomitantly increased ACSL4 in the co-exposure group. In summary, MBP and BPA co-exposure at human-relevant doses synergistically induces neurotoxicity in NSCs through glutathione metabolism disruption and subsequent ferroptosis. These findings underscore the importance of evaluating chemical mixtures rather than individual compounds in neurodevelopmental risk assessment.
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2026
·Vol. 53
·期 2
·e70110
·
IF 2.5
Guangwei Yang,Cong Yu,Chao Weng
Objective Abdominal aortic aneurysm (AAA) refers to a disease where the abdominal aorta progressively dilates to 3.0 cm or more, making it prone to rupture. The etiologic and pathophysiological mechanisms underlying the formation and development of AAA are not yet fully understood. A preliminary investigation was conducted into the effects of Kruppel-like factor 5 (KLF5) regulation of the nuclear factor erythroid-2-related factor 2/heme oxygenase 1 (NRF2/HO-1) signalling pathway on ferroptosis in AAA vascular smooth muscle cells (VSMCs). Methods ApoE −/− mice or primary VSMCs were induced with angiotensin II (Ang II). KLF5 overexpression was achieved through adenovirus injection in the mouse model, and ML385 (NFR2 inhibitor) was injected to explore the involvement of the NRF2/HO-1 pathway in KLF5-regulated ferroptosis, inflammation, phenotypic switching and calcium deposition. Ang II-treated VSMCs were transiently transfected to overexpress KLF5 and/or incubated with Erastin (ferroptosis inducer) or ML385. The abdominal aorta was sampled from AAA model mice, and VSMC supernatants were collected to perform functional assays. Results KLF5 expression was downregulated in abdominal aorta tissues from AAA mice. KLF5 overexpression ameliorated inflammatory response by reducing phenotypic switching in VSMCs and inhibited ferroptosis and vascular calcification by reducing oxidative stress. Induction of ferroptosis partially reversed the ameliorative effect of KLF5 on vascular calcification in VSMCs. KLF5 exerted antioxidant effects by increasing NRF2 nuclear translocation and upregulating HO-1. Inhibition of the NRF2/HO-1 pathway partially reversed KLF5 regulation of phenotypic switching and vascular calcification in VSMCs. Conclusion KLF5 may exert a protective effect by inhibiting ferroptosis and calcium deposition in VSMCs in AAA through regulation of the NRF2/HO-1 signalling pathway.
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Jun Liu,Jing Ren,Linlan Zhou,Kaiyue Tan,Donglin Du,Lei Xu,Wenfu Cao,Yudi Zhang
Ethnopharmacological relevance The limitations of modern medicine in mitigating the pathological process of diabetic kidney disease (DKD) necessitate novel, precise, and effective prevention and treatment methods. Huangqi, the root of Astragalus membranaceus Fisch. ex Bunge has been used in traditional Chinese medicine for various kidney ailments. Astragaloside IV (AS-IV), the primary pharmacologically active compound in A. membranaceus , is involved in lipid metabolism regulation; however, its potential in ameliorating renal damage in DKD remains unexplored. Aim of the study To elucidate the specific mechanism by which AS-IV moderates DKD progression. Materials and methods A murine model of DKD and high glucose-induced HK-2 cells were treated with AS-IV. Furthermore, multiomics analysis, molecular docking, and molecular dynamics simulations were performed to elucidate the mechanism of action of AS-IV in DKD, which was validated using molecular biological methods. Results AS-IV regulated glucose and lipid metabolism in DKD, thereby mitigating lipid deposition in the kidneys. Proteomic analysis identified 12 proteins associated with lipid metabolism regulated by AS-IV in the DKD renal tissue. Additionally, lipid metabolomic analysis revealed that AS-IV upregulated and downregulated 4 beneficial and 79 harmful lipid metabolites, respectively. Multiomics analysis further indicated a positive correlation between the top-ranked differential protein heme oxygenase (HMOX)1 and the levels of various harmful lipid metabolites and a negative correlation with the levels of beneficial lipid metabolites. Furthermore, enrichment of both ferroptosis and hypoxia-inducible factor (HIF)-1 signaling pathways during the AS-IV treatment of DKD was observed using proteomic analysis. Validation results showed that AS-IV effectively reduced ferroptosis in DKD-affected renal tubular epithelial cells by inhibiting HIF-1α/HMOX1 pathway activity, upregulating glutathione peroxidase-4 and ferritin heavy chain-1 expression, and downregulating acyl-CoA synthetase long-chain family member-4 and transferrin receptor-1 expression. Our findings demonstrate the potential of AS-IV in mitigating DKD pathology by downregulating the HIF-1α/HMOX1 signaling pathway, thereby averting ferroptosis in renal tubular epithelial cells. Conclusions AS-IV is a promising treatment strategy for DKD via the inhibition of ferroptosis in renal tubular epithelial cells. The findings of this study may help facilitate the development of novel therapeutic strategies.
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Frontiers in Pharmacology
·
2026
·
IF 5.4
Jie Weng,Songlian Liu,Yajun Tong,Kewei Tang,Leilan Yin,Site Bai,Ludi Ou,Qinghua Yin,Qiang Zhou
Introduction Cervical cancer ranks as the fourth most common malignancy among women worldwide. It is closely associated with the dysregulation of numerous genes and signaling pathways. Conventional treatments for cervical cancer often lead to adverse side effects and the development of drug resistance. Methods In this study, network pharmacology was employed to identify the active components and potential targets of Crocus sativus L. Molecular docking and surface plasmon resonance analyses were used to validate the interaction between lauric acid and a key target. Lauric acid‐modified gold nanoparticles (Au@LA) were synthesized and characterized. Results Twenty‐three active components and 819 potential targets of Crocus sativus L. were identified, with PTGS2 being the main target. Au@LA selectively inhibited HeLa cell proliferation, induced apoptosis, downregulated SLC7A11 and GPX4, and modulated oxidative stress markers. In macrophages, Au@LA shifted M2 polarization to the pro‐inflammatory M1 phenotype and modulated the PGE2/EP2/cAMP‐PKA signaling axis. Conclusion Our findings indicate that Au@LA has dual anti‐cervical cancer properties through inducing ferroptosis in HeLa cells and reprogramming macrophage polarization. It shows promise as a candidate for natural product‐based nanomedicine in cervical cancer therapy, potentially opening new avenues for more effective and targeted treatments in the future.
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FREE RADICAL BIOLOGY AND MEDICINE
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2026
·
IF 8
Pingping Zhao,Binjing Pan,Xiaoyu Lv,Lihua Ma,Jingfang Liu
Non-enzymatic glycation is an important post-translational modification of proteins, ultimately forming advanced glycation end products (AGEs). In a high-glucose environment, the glycation degree of transferrin (Tf) increases, leading to elevated levels of AGE-modified transferrin (AGE-Tf), which reduces the binding capacity of Tf for iron. However, the role of AGE-Tf-associated iron dysregulation in diabetic nephropathy remains unclear. In this study, human podocytes were treated in vitro with AGE-Tf prepared by incubating Tf with 5.6 or 33.3 mM glucose (hereafter termed 5.6-Glc-AGE-Tf and 33.3-Glc-AGE-Tf, respectively) in combination with iron. Additionally, plasmids encoding Tf with mutations at three glycation sites (K206 A/K296 A/K534A; MT-Tf) or wild-type Tf (WT-Tf) were packaged into adeno-associated viral vectors and administered to diabetic rats. Compared with podocytes treated with 5.6-Glc-AGE-Tf, podocytes treated with 33.3-Glc-AGE-Tf exhibited reduced viability and greater oxidative stress. After ferric-citrate addition, intracellular Fe 2+ was also higher in the 33.3-Glc-AGE-Tf group than in the 5.6-Glc-AGE-Tf group. The 33.3-Glc-AGE-Tf group showed decreased GPX4, Nrf-2, and SLC7A11 expression and increased ACSL4 expression. In vivo, diabetic rats receiving an empty vector (DM-empty-vector) or a wild-type Tf vector (DM-WT-Tf-vector) exhibited higher renal AGE-Tf, Fe 2+ , and oxidative stress levels; lower nephrin and podocin expression; ferroptosis-related alterations; mesangial cell proliferation and matrix expansion; increased interstitial collagen deposition; and focal nodular sclerosis. These alterations were attenuated in diabetic rats receiving the glycation-resistant mutant Tf vector (DM-MT-Tf-vector). Deferoxamine (DFO) or TBHQ (an Nrf-2 activator) ameliorated oxidative stress, iron dysregulation, and ferroptosis in AGE-Tf-treated podocytes and in the kidneys of diabetic rats receiving the WT-Tf vector, whereas LY294002 (a PI3K/AKT pathway inhibitor) primarily alleviated oxidative stress. These findings identify AGE-Tf-associated iron dysregulation as a potential therapeutic target in diabetic kidney disease.
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Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Xiang Li,Longlong Wu,Xuan Tian,Weiping Zheng,Mengshu Yuan,Xiaorong Tian,Huaiwen Zuo,Hongli Song,Zhongyang Shen
Hepatic ischemia-reperfusion injury (IRI) is an inevitable result of liver surgery. Steatotic livers are extremely sensitive to IRI and have worse tolerance. Ferroptosis is considered to be one of the main factors of organ IRI. This study is aimed at exploring the role of ferroptosis in the effect of heme oxygenase-1-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs) on steatotic liver IRI and its mechanism. An IRI model of a steatotic liver and a hypoxia reoxygenation (HR) model of steatotic hepatocytes (SHPs) were established. Rat BMMSCs were extracted and transfected with the Ho1 gene to establish HO-1/BMMSCs, and their exosomes were extracted by ultracentrifugation. Ireb2 was knocked down to verify its role in ferroptosis and cell injury in SHP-HR. Public database screening combined with quantitative real-time reverse transcription PCR identified microRNAs (miRNAs) targeting Ireb2 in HO-1/BMMSCs exosomes. miR-29a-3p mimic and inhibitor were used for functional verification experiments. Liver function, histopathology, terminal deoxynulceotidyl transferase nick-end-labeling staining, cell viability, mitochondrial membrane potential, and cell death were measured to evaluate liver tissue and hepatocyte injury. Ferroptosis was assessed by detecting the levels of IREB2, Fe2+, malondialdehyde, glutathione, lipid reactive oxygen species, glutathione peroxidase 4, prostaglandin-endoperoxide synthase 2 mRNA, and mitochondrial morphology. The results revealed that HO-1/BMMSCs improved liver tissue and hepatocyte injury and suppressed ferroptosis in vivo and in vitro. The expression of IREB2 was increased in steatotic liver IRI and SHP-HR. Knocking down Ireb2 reduced the level of Fe2+ and inhibited ferroptosis. HO-1/BMMSC exosomes reduced the expression of IREB2 and inhibited ferroptosis and cell damage. Furthermore, we confirmed high levels of miR-29a-3p in HO-1/BMMSCs exosomes. Overexpression of miR-29a-3p downregulated the expression of Ireb2 and inhibited ferroptosis. Downregulation of miR-29a-3p blocked the protective effect of HO-1/BMMSC exosomes on SHP-HR cell injury. In conclusion, ferroptosis plays an important role in HO-1/BMMSC-mediated alleviation of steatotic liver IRI. HO-1/BMMSCs could suppress ferroptosis by targeting Ireb2 via the exosomal transfer of miR-29a-3p.
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