BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2025
·
IF 4.2
Dejian Chen,Yu Wang,Xiaomin Wang,Xiaosa Si,Yajing Weng,Shengbing Liu,Weiwei Pan,Ying Xu,Yong Wang,Yaling Zhang
Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation and excessive production of reactive oxygen species (ROS). Hyperandrogen exposure can induce ovarian ferroptosis in polycystic ovary syndrome (PCOS). However, there is not enough direct evidence regarding ovarian ferroptosis in PCOS to prove the role of ferroptosis in PCOS and the underlying mechanism. Nuclear receptor coactivator 4 (NCOA4) expression in ovarian granulosa cells and its mechanism of mediating ferroptosis have not been studied. In this study, we aimed to investigate how iron overload in ovarian granulosa cells and hyperandrogen exposure-induced ferroptosis affect ovarian development in a PCOS model. Increased ferroptosis was observed in hyperandrogenic mice with PCOS and in 5α-dihydrotestosterone (DHT)-induced primary granulosa cells. Iron deposition increased significantly, followed by increased cellular Fe 2+ concentration, whereas ROS accumulation, malondialdehyde (MDA), glutathione (GSH), and the glutathione/oxidized glutathione (GSH/GSSG) ratio decreased. NCOA4 and transferrin receptor expression increased; however, ferritin heavy chain 1 expression decreased in ovarian tissues. Androgen receptor and NCOA4 showed increased colocalization in the ovarian granulosa cell layer. Notably, DHT induced ferroptosis by activating NOCA4-dependent ferritin autophagy. However, deferoxamine mesylate inhibited ferroptosis in the ovarian granulosa mice cells, ameliorating the PCOS phenotype. Steroid hormone biosynthesis, arachidonic acid metabolism, and unsaturated fatty acid pathways were most significantly affected, providing a reference for PCOS diagnosis and treatment and corresponding drug development.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Yu Guan,Jinyu Liu,Jing Yang,Sufang Chen,Weifeng Yao,Shengyuan Gong,Chunsheng Xiao,Mingqiang Li,Gangjian Luo,Ziqing Hei
Hepatic ischemia-reperfusion injury (IRI) is characterized by an acute surge of reactive oxygen species (ROS) upon reperfusion, leading to oxidative damage and cell death. Ferroptosis, a form of iron-dependent lipid peroxidation-driven cell death, has recently been implicated in hepatic IRI, compounding the injury. Here, we present an oxidation-responsive nanoparticle system designed to mitigate liver IRI by scavenging ROS and inhibiting ferroptosis. We synthesized a PEGylated poly(α-lipoic acid) (PEG-PαLA) copolymer that self-assembles into nanoparticles encapsulating the lipophilic antioxidant coenzyme Q10 (CoQ10). The PEG-PαLA/CoQ10 nanoparticles have an average diameter of ~100 nm and release CoQ10 preferentially under oxidative conditions. In vitro, the nanoparticles efficiently neutralized free radicals and protected hepatocytes from oxidative injury. In a mouse model of partial hepatic IRI, treatment with PEG-PαLA/CoQ10 nanoparticles significantly reduced liver injury markers, preserved liver histology, and abrogated lipid peroxidation, indicating suppression of ferroptosis. Our results demonstrated that PEG-PαLA/CoQ10 nanoparticle is a novel antioxidant nanomedicine that synergistically attenuates ROS-mediated damage and ferroptotic cell death in hepatic IRI. These findings highlight a promising strategy for protecting organs from ischemia-reperfusion damage by targeting oxidative stress and ferroptosis with responsive biomaterial carriers.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
·
2026
·
IF 8.2
Yafei Duan,Yangguang Gu,Zhe Zhang,Meng Xiao,Ruijie Zhu,Jitao Li
Polychlorinated biphenyls (PCB) are typical persistent organic pollutants widely present in the environment, which commonly contaminate coastal aquaculture waters. Clarifying their toxic effects on edible shrimp is of great significance for healthy aquaculture development and food safety. This study conducted a 14-day subchronic exposure of Litopenaeus vannamei to 1 ng/L and 10 ng/L PCB1254 via waterborne exposure simulating environmental pollution levels, and systematically explored the toxicological effects of PCB at different biological levels using integrated multi-omics techniques. The results showed that PCB exposure reduced the survival and ammonia stress tolerance of the shrimp, and induced histological alterations and oxidative stress in the gills, manifested as the accumulation of lipid peroxidation products and the disruption of redox homeostasis. It affected ferroptosis homeostasis in the gills by inducing iron accumulation and altering the expression of gene markers, disturbed the expression of antimicrobial peptide genes (e.g., ALF , Pen3 ), and increased the expression of inflammation-related genes (e.g., JNK , TNFα ). Furthermore, the metabolic patterns in the gills were also disrupted, especially the pathways of amino acid metabolism and ABC transporters, as well as arachidonic acid and tryptophan metabolites. In addition, intestinal histological morphology was damaged, and microbial communities were disturbed, manifested as reduced diversity, altered abundance of functional bacteria (e.g., Vibrio , Pseudoalteromonas , Bacteroides and Lactobacillus ), and disrupted metabolic functions (e.g., carbohydrate absorption, β -lactam resistance). Finally, the nutritional value of the muscle was impaired by reducing the contents of crude protein, total amino acids and delicious amino acids. In conclusion, this study revealed that exposure to environmentally relevant concentrations of PCB-1254 induced toxic effects on shrimp by triggering histological alterations, oxidative stress, ferroptosis, metabolic reprogramming and intestinal microbiota disorder, and altered their muscle nutritional quality.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 6
Chudong He,Yuanyuan Zhao,Mengdie Mo,Yuhong Su,Zhongquan Qi,Xiao Dong Chen,Weijie Zhou,Fei Yu
Ferroptosis is an iron-dependent programmed cell death modality characterized by the massive accumulation of lipid peroxides (LPO). However, the efficiency of ferroptosis is commonly limited by insufficient supply of iron ions and endogenous hydrogen peroxide (H 2 O 2 ) in the tumor cells. To overcome these drawbacks, MIL-100 NPs were synthesized via a microwave-assisted method to encapsulate β-lapachone (Lap), followed with the hyaluronic acid (HA) surface modification (designated as LMH NPs). LMH NPs exhibited GSH-responsive degradation in the tumor cells to release Lap and Fe 3+ . The released of Lap could generate H 2 O 2 via catalysis by tumor-overexpressed quinone oxidoreductase 1 (NQO1), leading to increased intracellular H 2 O 2 levels. The abundant production of H 2 O 2 could supply substrates for Fe 2+ -mediated Fenton reactions to produce toxic hydroxyl radicals (·OH), thereby promoting LPO accumulation and enhancing ferroptosis. Meanwhile, Fe 3 ⁺ released from LMH NPs was reduced to Fe 2+ through GSH consumption, which could diminish glutathione peroxidase 4 (GPX4) activity. In vitro and in vivo experiments confirmed that LMH NPs possessed effective targeted uptake and exhibited optimal tumor inhibition without significant toxic side effects. Overall, the integrated strategy presents a novel ferroptosis-based clinical approach for enhanced breast cancer therapy. Scheme 1 Preparation process and antitumor mechanisms of LMH NPs. (A) The preparation process of LMH NPs. (B) Antitumor mechanism of LMH NPs through inducing ferroptosis. (C) Lap undergoes a ‘‘futile redox cycling’’ process catalyzed by NQO1. Download: Download high-res image (119KB) Download: Download full-size image
✓ 已验证
DOI
PubMed
高影响因子
FITOTERAPIA
·
2023
·
IF 3.4
Nan Zhang,Junwei Zhang,Weiqi Cui,Deqiao Wu,Jingxian Zhang,Bo Wei,Lingbo Qu,Xia Xu
Artemisia argyi H.Lév. & Vaniot, a traditional Chinese medicine with a history spanning over two millennia, has been extensively used in folk medicine to treat dysmenorrhea, uterine bleeding and inflammation. Recent studies have demonstrated that the essential oil extracted from Artemisia argyi H.Lév. & Vaniot, known as AAEO, exhibits significant anti-tumor properties against liver and lung cancers. There is a scarcity of research on the potential impact of AAEO on pancreatic cancer (PC) cells. In this study, UPLC-MS/MS-based metabolomics method was established to evaluate the effect of AAEO on the proliferation of PC cells. The differential compounds included 5-oxoproline, glutamate, γ-glutamylcysteine, glutathione, arachidonic acid, adrenal acid and linoleic acid were detected by metabolomics, enriching in the γ-glutamyl cycle and polyunsaturated fatty acid metabolism, which were closely related to ferroptosis. Meanwhile, AAEO dramatically increased the levels of intracellular iron ion via up-regulation of TFR1, augmented reactive oxygen species and malondialdehyde in a dose-dependent manner by down-regulation of γ-glutamyl cycle through decreasing expressions of SLC7A11. Additionally, β-caryophyllene oxide, one of the main components of AAEO, could covalently bind to Cys in SW1990 cells to form a conjugate Cpo-Cys, resulting in the inhibition of glutathione synthesis. Importantly, the ferroptosis inhibitor deferoxamine significantly blocked the inhibitory effect of AAEO on SW1990 cells. Meanwhile, β-caryophyllene oxide, dihydro-β-ionone and α-bisabolol had strong binding force with GPX4, SLC7A11 and TFR1, respectively. These findings showed that AAEO induced ferroptosis via regulation of γ-glutamyl cycle by SLC7A11 and iron disorders by TFR1. Our study discovered AAEO as a potential therapeutic approach to induce ferroptosis to prevent or treat PC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Zhiwei Li,Jiaqi Bu,Xinyu Zhu,Hao Zhou,Kaiqun Ren,Paul K. Chu,Limin Li,Xiang Hu,Xiaofeng Ding
Programmed cell death receptor ligand 1 (PD-L1)/PD-1 signaling has been exploited to design inhibitors that deliver promising clinical outcome albeit with limited efficacy. Herein, we prepare graphene oxide (GO)-PEI-PEG with low cytotoxicity and long stability and GO-PEI-PEG delivers PD-L1 siRNAs to hepatocellular carcinoma (HCC) cells by the endocytosis-lysosome pathway. The functional GO-PEI-PEG/PD-L1 siRNAs decrease PD-L1 and PD-1 abundance, increase pro-inflammation cytokine IFN-γ and TNF-α release, and improve the proliferation activity of Jurkat T cells. Since GO-PEI-PEG targets the mouse liver effectively, the intrahepatic tumors in C57BL/6 mice are treated with GO-PEI-PEG/Pd-l1 siRNAs via the tail vein, resulting in shrinkage of the HCC tumors and boosting the anti-tumor efficacy in combination with oral sorafenib. A single treatment improves the total CD3 + and cytotoxic CD8 + T cell infiltration in the HCC tumor tissues and even spleen and upregulates the expression of Perforin, Gzmb, Ifng, Il-1b and Tnfa in the tumors after the combined treatment. Both the single and combined treatments enhance reactive oxygen species (ROS) accumulation, and improved HCC ferroptosis. The results suggest that GO-PEI-PEG delivered PD-L1 siRNAs combined with oral sorafenib can activate the adaptive immunity and tumor ferroptosis and reveal an effective therapy to treat advanced HCC patients.
✓ 已验证
DOI
PubMed
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yuxi Guo,Xuemei Jia,Pengli Du,Jie Wang,Yao Du,Bolin Li,Yucong Xue,Jianming Jiang,Yanru Cai,Qian Yang
Ethnopharmacological relevance Xianglianhuazhuo formula (XLHZ) has a potential therapeutic effect on chronic atrophic gastritis (CAG). However, the specific molecular mechanism remains unclear. Aim of the study To evaluate the effect of XLHZ on CAG in vitro and in vivo and its potential mechanisms. Methods A rat model of CAG was established using a composite modeling method, and the pathological changes and ultrastructure of gastric mucosa were observed. YY1/miR-320a/TFRC and ferroptosis-related molecules were detected. An MNNG-induced gastric epithelial cell model was established in vitro to evaluate the inhibitory effect of XLHZ on cell ferroptosis by observing cell proliferation, migration, invasion, apoptosis, and molecules related to ferroptosis. The specific mechanism of action of XLHZ in treating CAG was elucidated by silencing or overexpression of targets. Results In vivo experiments showed that XLHZ could improve the pathological status and ultrastructure of gastric mucosa and inhibit ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway. The results in vitro demonstrated that transfection of miR-320a mimics inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. MiR-320a targeted TFRC and inhibited ferroptosis. Overexpression of TFRC reversed the inhibitory effect of miR-320a overexpression on cell proliferation. The effect of XLHZ was consistent with that of miR-320a. YY1 targeted miR-320a, and its overexpression promoted ferroptosis. Conclusion XLHZ inhibited ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway, ultimately impeding the progression of CAG.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2021
·
IF 8.128
Yawen Wei,Zhihua Wang,Jie Yang,Rui Xu,Huizi Deng,Siyu Ma,Tianxu Fang,Jun Zhang,Qi Shen
With the continuous development of cancer nanotechnology, an important trend in the research is to combine the broad application prospects of functional nanomaterials with recent biological discoveries and technological advances. Herein, a cancer cell membrane-camouflaged gold nanocage loading doxorubicin (DOX) and l -buthionine sulfoximine (BSO) (denoted as [email protected] /B NCs) was constructed as an innovative nanoplatform to confer promising cancer combination therapy by evoking effective ferroptosis and immune responses. Briefly, the loading of BSO and DOX could induce ferroptosis through simultaneous effective glutathione (GSH) consumption and reactive oxygen species (ROS) accumulation. Gold nanocages (AuNCs) with distinct anti-tumor application performance was utilized as ideal nanocarrier for drug loading, evoking photothermal effects and photochemical catalysis to generate more ROS under near-infrared (NIR) irradiation. Moreover, [email protected] /B NCs-mediated photothermal therapy (PTT) combined with ROS production could repolarize the tumor-associated macrophages (TAMs) from pro-tumor (M2) phenotype to anti-tumor (M1) phenotype, thus improving tumor-suppressive immune environment and then promoting the activation of effector cells and release of pro-inflammatory cytokines, in which the antitumor responses were evoked robustly in a methodical approach. The anti-tumor effects in vivo implied that [email protected] /B NCs could significantly inhibit tumor growth without severe toxicity. Hence, this homotypic targeting nanosystem could offer an auspicious anticancer access by triggering combination cancer therapy via ferroptosis and tumor-associated macrophage repolarization mechanism.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2025
·
IF 4.2
Yongpeng Fang,Xudong Niu,Weifang Zhao,Huali Zhang
Myocardial ischemia/reperfusion (I/R) injury is a major cause of various adverse cardiovascular outcomes associated with excessive mitophagy and cardiomyocyte ferroptosis. Paired-related homeobox 1 (PRRX1) is a transcriptional factor involved in cardiovascular injury. However, whether and how PRRX1 regulates excessive mitophagy and cardiomyocyte ferroptosis during myocardial I/R injury remains unclear. Oxygen-glucose deprivation and reperfusion (OGD/R)-treated AC16 cardiomyocytes and myocardial I/R-induced rats were used as in vitro and in vivo models. Our results showed that PRRX1 expression was upregulated in AC16 cells after OGD/R treatment. PRRX1 silencing mitigated OGD/R-induced excessive mitophagy by increasing the mitochondrial membrane potential, adenosine triphosphate and p62 levels, and reducing LC3 II/I level in AC16 cells. In addition, PRRX1 knockdown attenuated OGD/R-induced lactate dehydrogenase (LDH) release and cardiomyocyte ferroptosis by decreasing reactive oxygen species, Fe 2+ and acyl-CoA synthetase long-chain family member 4 (ACSL4) levels, and increasing glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels. Furthermore, PRRX1 transcriptionally promoted FK506 binding protein 5 (FKBP5), and increased p38 MAPK activation in AC16 cells. FKBP5 overexpression reversed the effects of PRRX1 silencing on excessive mitophagy and cardiomyocyte ferroptosis in OGD/R-treated AC16 cells. These effects were mitigated by a p38 MAPK inhibitor. Finally, PRRX1 downregulation mitigated myocardial I/R injury by reducing heart infarction and creatine kinase-myocardial band (CK-MB) levels in rat models. These findings demonstrate that PRRX1 silencing attenuates OGD/R-induced excessive mitophagy and cardiomyocyte ferroptosis by decreasing FKBP5 expression and inactivating p38 MAPK signaling, indicating the cardioprotective potential of PRRX1 silencing in myocardial I/R injury.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Ya Ting Fan,Dong Qiao Peng,Jing Lin Shen,Jun Hao Cui,Xin Yue Yang,Jin Ge Zhang,Yong Cheng Jin
Excessive copper (Cu) has the potential risk to ecosystems and organism health, with its impact on dairy cow mammary glands being not well-defined. This study used a bovine mammary epithelial cell (MAC-T) model to explore how copper excess affects cellular oxidative stress, autophagy, ferroptosis, and protein and lipid biosynthesis in milk. Results showed the increased intracellular ROS, MDA, and CAT ( P < 0.05), alongside decreased T-SOD and GSH in CuSO 4 -treated cells ( P < 0.05). Transmission electron microscopy and Ad-mCherry-GFP-LC3B assays revealed significant autophagosome accumulation in CuSO 4 exposed cells ( P < 0.05). Additionally, CuSO 4 exposure modulated autophagy markers, evidenced by upregulation of genes such as LC3, ATG5, JNK1, and Beclin1, and downregulation of genes such as ATG4B, and p62 ( P < 0.05). CuSO 4 also led to notable mitochondrial changes, including size reduction, membrane rupture, and cristae loss, and reduced expression of the ferroptosis inhibitor GPX4 ( P < 0.05). The expression of mTOR, HIF-1α and β-catenin signaling pathway were inhibited in differentiated MAC-T cells by CuSO 4 exposure ( P < 0.05), activated autophagy through activation of the AMPK-mTOR pathway which in turn affected downstream levels of genes related to milk protein and lipid. In conclusion, excessive copper induces oxidative stress in MAC-T cells, promoting autophagy through JNK-Bcl2, Beclin1-Vps34 and AMPK-mTOR pathways, leading to cell ferroptosis, as well as inhibits the cellular biosynthesis of milk protein and lipid.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Jinyue Sun,Hui-Ling Shen,Jia-Neng Pan,Ting Yu,Wen-Wen Zhou
The ferrous sulfate (FeSO 4 )-based mechanism causing ferroptosis-like death in Pseudomonas aeruginosa was investigated. FeSO 4 triggered ferroptosis in P. aeruginosa planktonic cells, decreased the ratio of glutathione to oxidized glutathione, and resulted in the increase of reactive oxygen species and lipid peroxidation, damaging the integrity of the cell membrane. In addition, FeSO 4 prevented P. aeruginosa from forming biofilms on the surface of stainless steel, glass, and high-density polyethylene. Transcriptome analyses indicated that there were 412 up-regulated genes and 782 down-regulated genes following FeSO 4 treatment. FeSO 4 increased the cross-linking density of a carboxymethyl chitosan (CMCS) agar-based film, reducing its water solubility, swelling degree, water vapor permeability, and oxygen permeability. Finally, FeSO 4 @CMCS agar-based film showed potential antibacterial ability against the growth of P. aeruginosa in grapes, purple kale, and cherry tomatoes during storage.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Chen Yukun,Chen Yuanyuan,Wang Zhenzhi,Yang Lian,Zhang Yu,Zhang Zhanxia,Jia Lijun
Reversing the hypoxic microenvironment of tumors is an important method to enhance the synergistic effect of tumor treatment. In this work, we developed the nanoparticles called Ce6@HGMOF, which consists of a photosensitizer (Ce6), glucose oxidase (GOX), chemotherapy drugs (HCPT) and an iron-based metal-organic framework (MOF). Ce6@HGMOF can consume glucose in tumor cells through “starvation therapy”, cut off their nutrition source, and produce gluconic acid and hydrogen peroxide (H 2 O 2 ). Utilizing this feature, Ce6@HGMOF can produce oxygen through catalase-like catalytic activity, thereby reversing the hypoxic microenvironment of tumors. This strategy of changing the hypoxic environment can help to slow down the growth of tumor blood vessels and improve the drug-resistant microenvironment to some extent. Meanwhile, increasing the supply of oxygen can enhance the effect of photodynamic therapy (PDT) and enhance the oxidative stress damage caused by reactive oxygen species (ROS) in tumor cells. On the other hand, cancer cells usually produce higher levels of glutathione (GSH) to adapt to high oxidative stress and protect themselves. The Ce6@HGMOF we designed can also consume GSH and induce ferroptosis of tumor cells through Fenton reaction with H 2 O 2 , while enhancing the effect of PDT. This innovative synergistic strategy, the combination of PDT/ferroptosis /starvation therapy, can complement each other and enhance each other. It has great potential as a powerful new anti-tumor paradigm in the future.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）