MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2025
·
IF 3.6
Lanlan Cheng,Jie Zhang,Yungai Xiang,Li Tan
Spontaneous abortion (SA) refers to the loss of a pregnancy without external intervention. The runt-related transcription factor 3 (RUNX3) is associated with gestational disorders in view of previous studies. However, RUNX3 has not been reported in SA. RUNX3 is significantly upregulated in the placental villi of abortion patients based on the GSE123719 microarray data. Herein, we further validated and found that the expression of RUNX3 in placental villi of SA women was higher than those of induced abortion (IA) women. In vitro , we constructed human RUNX3 overexpression or interference adenovirus vectors to modulate RUNX3 expression in trophoblast cells. Our findings revealed that RUNX3 overexpression accelerated trophoblast cell ferroptosis, while RUNX3 knockdown alleviated erastin-induced ferroptosis. Subsequently, the dual luciferase reporter assay was performed to confirm that RUNX3 bound to the GDF15 promoter to transcriptionally repress GDF15 transcriptional activity. Importantly, GDF15 attenuated the pro-ferroptosis effects of RUNX3 on HTR-8/SVneo cells. In vivo , mouse RUNX3 interference adenovirus vectors were used to silence RUNX3 in mice. The results presented that the reduction of RUNX3 inhibited embryo adsorption rate in SA mice, involving ferroptosis and the interaction between RUNX3 and GDF15. Taken together, this study established that RUNX3 advanced SA progression by enhancing trophoblast ferroptosis via transcriptionally repressing GDF15. These findings may provide novel therapeutic strategies for SA management.
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高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jiayang Luo,Luyao Xu,Jing Feng,Kexin Xu,Peilin Tian,Xianyue Bai,Shihao Xu,Liewei Wen,Cuixia Lu,Jiaxing Song
Photodynamic therapy (PDT) induces apoptosis in cancer cells by generating cytotoxic reactive oxygen species (ROS); however, this effect is constrained by the intrinsic antioxidant mechanisms of the cells and the hypoxic conditions of the tumor microenvironment (TME). To overcome these limitations, a novel ferroptosis-boosted nanophotosensitizer (FCE NPs) is developed after loading alkaloid evodiamine based on an acid-responsive nanoplatform (FC NPs) composed of ferric ions and Chlorin e6 (Ce6). Upon exposure to laser irradiation, the photosensitizer Ce6 efficiently generates singlet oxygen (1O2), which depletes glutathione (GSH), thereby disrupting the redox homeostasis within tumor cells and leading to the oxidation of cellular unsaturated lipid into lipid peroxides (LPO). Additionally, the Fenton reaction between released Fe(III) ions and H2O2 in the TME produces highly cytotoxic hydroxyl radicals (•OH), a form of ROS, causing the accumulation of LPO together with 1O2 to trigger ferroptosis. Following the incorporation of evodiamine, the integrated nanoplatform FCE NPs exhibited excellent antitumor activity through high-performance ferroptosis by inhibiting a glutathione peroxidase 4 (GPX4) level. It was also observed that the key regulator of Wnt signaling pathway β-catenin was downregulated, suggesting the inhibition of FCE NPs on the Wnt signaling pathway. Therefore, this study demonstrated that the FCE NPs could lead to the explosive production of ROS and simultaneous inhibition of GPX4/GSH pathways and the Wnt signaling pathway in colorectal cancer, significantly amplifying the tumoricidal efficacy of PDT through the synergistical sensitization of ferroptosis. This approach offers a promising strategy for the clinical application of ferroptosis therapy.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Cong Zhang,Yangkun Xiong,Mingyang Gong,Haixia Zhao,Shan Li,Xin Chen,Xiaochuan Ye,Zhenpeng Qiu
Hyperuricemic nephropathy, a common subtype of chronic kidney disease (CKD), has become an important global public health issue and is closely related to the dramatic increase in fructose consumption. Pachymic acid, the primary active ingredient of the edible fungal herb Poria cocos, has demonstrated the protective capacity against renal injury, but its beneficial effect on hyperuricemic nephropathy remains unclear. In this study, a fructose-diet-induced hyperuricemia nephropathy mouse model was established to reveal the efficacy of pachymic acid in inhibiting hyperuricemic nephropathy the progression. Our results showed that pachymic acid restored abnormal renal function indexes and pathological manifestations such as tubular dilatation and glomerular fibrosis in fructose-fed mice. Transcriptome sequencing results showed marked alterations in glutathione metabolism and ferroptosis signaling pathways in the kidneys of fructose-fed mice after pachymic acid treatment. Mechanistically, pachymic acid activated the Nrf2/GPX-4 signaling pathway by directly binding to Nrf2 and promoting its nuclear translocation, thereby inhibiting ferroptosis, oxidative stress, and inflammatory responses in the kidneys of fructose-fed mice. Consistent results were observed in uric acid-treated HK-2 cells. Notably, both Nrf2 inhibitor ML385 and GPX-4 inhibitor RSL3 treatments reversed the protective effects of pachymic acid against renal injury by suppressing ferroptosis in vitro and in vivo. Summary, our study provides compelling evidence that pachymic acid ameliorates renal injury in fructose-fed mice by inhibiting ferroptosis through targeted activating an Nrf2/GPX-4 pathway, suggesting that dietary supplementation with Poria cocos or pachymic acid might be an effective strategy for CKD prevention, particularly in the subtype of fructose-diet-driven hyperuricemic nephropathy.
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高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Liang He,Hao Liang,Jixue Wang,Annan Liu,Lei Li,Ji Lu,Ze Wang,Andrew K. Whittaker,Quan Lin
Metastasis prostate cancer (PCa) precision detection and effective treatment remain significant challenge in clinic. Ferroptosis brought promising therapeutic strategy for the treatment of metastatic PCa, effectively inducing ferroptosis in PCa cells represents key to improve therapeutic efficacy. Herein, we developed a multifunctional nanoplatform Fe/Au nanodots-bombesin (FGN-BBN) as the ferroptosis nano-inducer to generate large amount of ROS to induce ferroptosis through an "open-source throttling" strategy for targeted imaging-guided therapy of metastatic PCa. On the one hand, FGN-BBN serves as an efficient biomimetic nanozyme and photothermal agent, exhibiting great POD-like activity and generating abundant reactive oxygen species (ROS) via photothermal-enhanced chemodynamic therapy (CDT) to induce ferroptosis, which is achieving “open source” aspect. On the other hand, FGN-BBN exhibit GPx-like activity that depletes overexpressed glutathione (GSH) within the tumor microenvironment, thereby preventing the neutralization of ROS and achieving the “throttling” effect. Furthermore, bombesin facilitates targeted delivery of the nanozyme to metastatic PCa cells, synergistically enhancing ferroptosis activity. In terms of diagnosis, FGN-BBN possesses targeted recognition capabilities and enables multimode bioimaging including fluorescence (FL), computed tomography (CT), and magnetic resonance imaging (FL/CT/MRI), allowing for the “visualization” of tumor localization and real-time imaging-guided therapy. In summary, the multifunctional nanoplatform integrates multienzyme activity, targeted recognition, multimodal imaging, photothermal therapy, and CDT to induce high-efficiency ferroptosis, offering an effective theranostic strategy for metastatic PCa.
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Biomaterials Advances
·
2025
·
IF 6
Zhidong Lin,Luoqi Mai,Huitong Luo,Zetao Wang,Yongpeng Lin,HongShen Wang,Shaohua Chen,Guoyi Su,Xulin Hu,Bolai Chen,Xiaodong Cao
Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain, characterized by the ferroptosis of nucleus pulposus cells (NPCs) and imbalance in reactive oxygen species (ROS) metabolism. Icariin (ICA), an active compound from traditional Chinese medicine, scavenges ROS and inhibits ferroptosis, but its poor water solubility and low bioavailability limit clinical use. A dual-crosslinked hydrogel (HP@ICA) is developed to address these challenges. Cyclodextrin is integrated into polyvinyl alcohol to enhance ICA loading via hydrophobic interactions. Methacrylic acid and phenylboronic acid are incorporated into hyaluronic acid, enabling dynamic bonding with polyvinyl alcohol. Ultraviolet crosslinking creates a secondary crosslinked hydrogel with pH and ROS responsiveness, self-healing properties, and improved ICA solubility, increasing its water solubility tenfold. Enhanced solubility boosts ICA's free radical scavenging capacity by 103 %, suppressing ferroptosis and promoting NP cell regeneration, as demonstrated by reduced iron ion concentrations, lower malondialdehyde levels, and restored glutathione peroxidase 4 activity. Ferroptosis inhibition facilitates type II collagen production in NP cells. Mechanistic studies reveal activation of the Nrf2-GPX4 pathway as key to regeneration. These findings suggest a promising regenerative therapeutic approach for IVDD.
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CHEMICO-BIOLOGICAL INTERACTIONS
·
2025
·
IF 5.4
Lin-Song Teng,Zhen-Dong Ying,Xiao-Han Sun,Hao-Cheng Hou,Shi-Dong Qiu,Peng Liu,Ke-Jing Li,Lei Zhang,Xie-Huang Sheng
Ferroptosis is an iron-dependent form of regulated cell death characterized by lethal lipid peroxidation and implicated in various human diseases. Despite intensive research, clinically applicable ferroptosis inhibitors remain unavailable. In this study, we identify formoterol, a β 2 -adrenergic agonist widely used to treat asthma and COPD, as a potent and selective ferroptosis inhibitor through scaffold-based screening of FDA-approved drugs. Formoterol confers robust protection against ferroptotic cell death induced by diverse triggers across multiple human and rodent cell lines, functioning independently of classical pathways such as GPX4, FSP1, or iron chelation. Mechanistic studies reveal that formoterol suppresses ferroptosis by directly scavenging lipid peroxyl radicals, mediated by its unique ortho -amino phenol moiety. In vivo, formoterol significantly alleviates acetaminophen-induced acute liver injury, reducing hepatic lipid peroxidation and preserving tissue integrity. These findings establish formoterol as a clinically approved agent with previously unrecognized anti-ferroptotic activity, offering a compelling example of drug repurposing to accelerate the development of ferroptosis-targeted therapies.
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高影响因子
ACS Nano
·
2025
·
IF 16
Chenqian Feng,Qiuting Wang,Susu Xiao,Yuanli Yang,Bo Chen,Hui Li,Min Mu,Rangrang Fan,Haifeng Chen,Bo Han,Gang Guo
Spinal cord injury (SCI) causes irreversible neurological damage largely due to secondary processes such as ferroptosis and inflammation response, which hinder functional recovery and lack effective targeted treatments. Ferroptosis, an iron-dependent form of cell death driven by oxidative stress, and a pro-inflammatory microenvironment contribute significantly to neuronal loss after SCI. To address these challenges, we developed MCPAD, an injectable, self-healing nanocomposite hydrogel incorporating metformin-loaded PLGA nanoparticles (Met@PLGA NPs) and phenol-derived dynamic cross-linked network (CPAD). This multifunctional platform enables targeted suppression of ferroptosis and immunomodulation. In vitro, MCPAD significantly enhanced neuronal viability by regulating iron homeostasis and upregulating antioxidant defenses. In vivo, it reduced reactive oxygen species (ROS) accumulation, glial scarring, and inflammatory cytokine expression, while promoting axonal regeneration and synaptic remodeling. Treated animals exhibited greatly improved locomotor recovery and tissue preservation. Biochemical assessments confirmed systemic biosafety. These findings demonstrate the therapeutic potential of MCPAD as a biological responsive platform that reprograms the injury microenvironment to support functional neural repair after SCI.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Jingjing Chen,Lu Zhou,Mengxin Li,Jun Wang,Yaru Chen,Jing Xia,Yue Lin,Huizhen Chen,Zibo Dong
Chronic Intermittent Hypoxia (CIH) is a central pathological feature of diseases such as obstructive sleep apnea hypopnea syndrome (OSAHS), which induces oxidative stress in lung tissues and leads to lung injury. Atraric acid (AA), a lichen-derived compound, has been reported to possess anti-inflammatory and antioxidant activities. In this study, we investigated the functions and mechanisms of AA in CIH-induced lung injury by constructing a CIH mouse model and an in vitro hypoxia/reoxygenation model in MLE-12 cells. Various methods were employed, including hematoxylin and eosin (H&E) staining, biochemical assay kits, quantitative polymerase chain reaction (qPCR) analysis, protein blotting, immunofluorescence, and flow cytometry. The results showed that AA pretreatment significantly attenuated pathological injury of mouse lung tissue, reduced pulmonary edema, reactive oxygen species (ROS) and malondialdehyde production, as well as the depletion of total antioxidant capacity, catalase and glutathione, and lowered the expression levels of inflammatory factors. Mechanistic studies showed that AA up-regulated solute transport family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression and down-regulated prostaglandin-endoperoxide synthase 2 (PTGS2) through activation of the Nrf2 signaling pathway, whereas the Nrf2 inhibitor ML385 completely blocked this protective effect. In conclusion, the present study demonstrates that AA targets the Nrf2 axis, attenuated CIH-induced inflammation, alleviates ROS accumulation, and blocks the vicious cycle of oxidative stress, ferroptosis, and inflammation, making it a promising therapeutic strategy for the treatment of CIH-induced lung injury.
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Advanced Science
·
2024
·
IF 14.3
Kai Yuan,Yiqi Yang,Yixuan Lin,Feng Zhou,Kai Huang,Shengbing Yang,Weiqing Kong,Fupeng Li,Tianyou Kan,Yao Wang,Caiqi Cheng,Yakun Liang,Haishuang Chang,Jie Huang,Haiyong Ao,Zhifeng Yu,Hanjun Li,Yihao Liu,Tingting Tang
The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.
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RSC Advances
·
2024
·Vol. 14
·期 18
·12864-12872
·
IF 3.9
Lili Zhong,Datian Fu,Jin Xu,Linyan Tan,Haimei Wu,Min Wang
Ferroptosis is a newly discovered iron-dependent form of regulated cell death associated with high levels of hydroxyl radical (˙OH) production. Meanwhile, lysosome dysfunction has been shown to be one of the causes of ferroptosis. Although a variety of ˙OH-responsive fluorescent probes have been developed for detecting intracellular ˙OH in living cells, there are still only few lysosome-targeted probes to monitor the variation in lysosomal ˙OH levels during ferroptosis. Herein, we report a novel ˙OH-specific fluorescent probe HCy-Lyso, which is composed of the hydrocyanine and morpholine moiety. Upon treatment with ˙OH, its hydrocyanine unit was converted to the corresponding cyanine group, thus leading to a large π-conjugation extension of HCy-Lyso, accompanied by a significant fluorescence off–on response. Moreover, after reacting with ˙OH in an acidic environment, the protonation product of HCy-Lyso exhibits a higher fluorescence enhancement, which is suitable for detecting lysosomal ˙OH variation. HCy-Lyso has been utilized for imaging endogenous ˙OH in living cells under phorbol myristate acetate (PMA) stimuli and monitoring the changes in lysosomal ˙OH levels during ferroptosis. Thus, our study proposes a new strategy to design lysosome-targeted and ˙OH-responsive fluorescent probes to investigate the relationship between lysosomes and ferroptosis.
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ADVANCED MATERIALS
·
2025
·
IF 26.8
Zekun Wang,Fangyuan Chen,Zhongkun Wang,Mengru Wu,Man Jiang,Zhekang Zheng,Yingying Li,Qing Li,Qingqing Wang,Dongdong Sun,Qingqing Miao
Nanozyme-driven ferroptosis provides a promising therapeutic strategy against drug-resistant bacterial infections by inducing iron overload and oxidative stress. However, bacterial metal transport proteins (MTP) and antioxidant systems can reduce iron accumulation and lipid peroxidation, limiting the efficacy of ferroptosis-based therapies and promoting resistance. Single-atom and chiral nanozymes, with their high atomic utilization and catalytic specificity, may provide an effective approach to overcoming bacterial defense mechanisms, which has been not exploited. In this study, we report D-chiral single-atom iron–carbon dot nanozymes (DFe-NSC) for effective bacterial infection treatment. Compared to L-chiral form (LFe-NSC), DFe-NSC exhibits significantly higher peroxidase (POD)-like and glutathione peroxidase (GPx)-like activities. The enhanced catalytic activity promotes reactive oxygen species (ROS) generation and glutathione depletion, disrupting bacterial redox homeostasis. More intriguingly, DFe-NSC more effectively modulates the expression and iron-regulatory function of MTP (including Fur and FtnA) than LFe-NSC. This will induce substantial accumulation of Fe 2 ⁺ intracellularly and thereafter lipid peroxidation, thereby facilitating the bactericidal effects of ferroptosis-like cell death. Resultantly, DFe-NSC exhibit markedly enhanced antibacterial and antibiofilm activities in diabetic infected wound and osteomyelitis models. This study introduces a chiral catalysis–MTP regulation strategy to induce bacterial ferroptosis-like death, providing a promising alternative for drug-resistant infection treatment.
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高影响因子
Nano Today
·
2022
·
IF 18.962
Xinghua Yu,Ying-Chuan Zhang,Xing Yang,Ziyang Huang,Tianfu Zhang,Liusi Yang,Wenjing Meng,Xiaotong Liu,Ping Gong,Alessandra Forni,Zheng Zheng,Bilu Liu,Pengfei Zhang,Lintao Cai,Ben Zhong Tang
Oxygen-dependent photodynamic therapy (PDT) for cancer treatment based on aggregation-induced emission luminogen (AIEgen) photosensitizer shows limited efficiency in the hypoxic tumor microenvironment (TME). To overcome tumor hypoxia-induced PDT resistance, a bonsai-inspired oxygen self-sufficient photodynamic cancer therapeutic system was developed based on AIEgen/vermiculite nanohybrid . Ultrathin nanosheets (NSs) were synthesized by lithium-ion intercalation from potting soil vermiculite for AIEgen photosensitizer (DCPy) loading through electrostatic attraction to produce NSs@DCPy (nano bonsai). When NSs@DCPy was absorbed by hypoxic the tumor and exposed to white light radiation, the NSs@DCPy could not only produce 1 O 2 and·OH but also catalyze the H 2 O 2 to generate O 2 for alleviating hypoxia significantly improving PDT efficacy. Surprisingly, NSs@DCPy could induce ferroptosis of the tumor by iron overload and depleting glutathione (GSH). Therefore, we provide a bonsai-inspired AIEgen-vermiculite nanohybrid platform for ferroptosis-assisted oxygen self-sufficient photodynamic cancer therapy.
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