JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Ning-Ning Huang,Ping-An Jian,Jia-Yu Du,Wen-Na Cai,Tian-Ning Yang,Zhi-Juan Wang,Shi-Yong Zhu,Kai Guo,Jin-Long Li,Chi-Chiu Wang,Xue-Nan Li
Global health issues have been heightened by di-(2-ethylhexyl) phthalate (DEHP), a commonly utilized plasticizer, due to its liver toxicity and potential to cause liver damage. Ferroptosis, a type of nonapoptotic cell death reliant on iron, is associated with multiple liver disorders. This research aimed to explore the role and mechanisms of ferroptosis in DEHP-induced liver toxicity in chickens. In vivo experiments showed that DEHP exposure caused liver damage. Transcriptomic analysis revealed that DEHP exposure activated ferroptosis and significantly upregulated myo-inositol oxygenase (MIOX) expression. Subsequent in vitro experiments using LMH cells revealed that reducing MIOX levels diminished ferroptosis caused by mono- (2-ethylhexyl) phthalate (MEHP), DEHP’s main metabolite, through the stimulation of the STAT3 signaling pathway. Our findings highlight the important role of MIOX in DEHP-induced liver injury via STAT3 signaling pathway. This study provides new evidence that MIOX is a potential therapeutic target for iron toxicosis associated liver diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Jianxiang Xu,Yingying Wang,Gareth R. Williams,Yilu Zheng,Yanyan Zhang,Tong Wang,Chengrong Du,Yu Wang,Ying-Li Wu,Li-Min Zhu
Excessive intracellular accumulation of metal ions results in metal-dependent programmed cell death, including ferroptosis and cuproptosis. However, cancer cells have defences against these processes, which allow them to resist therapy. Therefore, this work reports a laser-controlled cascade bioreactor based on gold and silica-coated Cu- and Mn-doped iron oxide nanocrystals (IONCs) loaded with the drug disulfiram (DSF). The resultant DSF/IONC@Au/MSN-TA nanoparticles (NPs) can deliver synergistic tumor metalloimmunotherapy through ferroptosis and cuproptosis. Under near-infrared laser (NIR) irradiation, DSF is released and chelates with Cu 2+ to form Cu + species in cancer cells, which leads to mitochondrial dysfunction via cuproptosis. The presence of gold nanodots on the DSF/IONC@Au/MSN-TA NPs allows them to consume intracellular glucose and sensitize cancer cells to cuproptosis. The DSF/IONC@Au/MSN-TA NPs induce ferroptosis via waterfall-like cyclic catalytic reactions, and iron ions released by the NPs consume glutathione (GSH), thereby enhancing sensitivity to cuproptosis and ferroptosis. The presence of manganese ions augments the efficacy of these processes and additionally allows imaging to be performed. A detailed physicochemical characterization of the NPs is reported, along with a series of assays to study the mechanisms of their biocatalytic activity. The NPs’ biocompatibility is also established, and they are found to be appropriate for bioimaging and theranostic applications. Our work thus offers an innovative route for targeted tumor metalloimmunotherapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2026
·
IF 9.6
Yong Huang,Tao Quan,Bowen Li,Chaohui Zhen,Haiqian Zhang,Zhiyao Li,Chongzhi Wu,Rui Liang,Lihe Sun,Xin Xie
Triple-negative breast cancer (TNBC), lacking effective therapeutic targets, is highly aggressive, prone to metastasis, and associated with poor prognosis, highlighting the necessity for innovative therapeutic strategies. Ferroptosis, an emerging form of iron-dependent programmed cell death, presents a promising treatment approach. However, its effectiveness is often hindered by adaptive resistance within the tumor microenvironment and inefficient drug delivery. To address these limitations, the glutathione (GSH)-responsive disulfide linker (-SS-) was utilized to engineer rhein (Rhe, chemotherapeutic agent) and ferrocene (Fc, ferroptosis booster) into the self-assembling small-molecule prodrug RSSF. Sorafenib (SOR), a ferroptosis inducer, was stably loaded into RSSF via a simple nanoprecipitation method, yielding the newly nanoprodrug designated as SOR@RSSF nanoparticles (NPs) for the combination therapy of TNBC. SOR@RSSF NPs exhibit markedly enhanced cellular uptake and enable the highly specific and synchronous release of Rhe, Fc, and SOR in response to intracellular GSH levels. Notably, Fc efficiently generates hydroxyl radicals (•OH) through the Fenton reaction, thereby inducing pronounced oxidative stress, while SOR concurrently impaired the cellular ferroptosis defense machinery. Combined with the chemotherapeutic activity of Rhe, the resulting lipid peroxide (LPO) accumulation and GSH depletion synergistically trigger both ferroptosis and apoptosis selectively in tumor cells. In a 4T1 tumor-bearing mouse model, SOR@RSSF NPs significantly inhibited tumor progression while maintaining a favorable biosafety profile. Overall, this study presents a promising ferroptosis-sensitizing strategy using a nanoprodrug delivery system for combination therapy against TNBC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANTIOXIDANTS & REDOX SIGNALING
·
2026
·
IF 6.1
Ze Wang,Kejie Chang,Ke Zhang,Pei Wang,Guangjian Bai,Zhenhua Wang,Jian Xiao,Xin Tong,Jun Zhao
Aims:Esophageal squamous cell carcinoma (ESCC) is among the most lethal malignancies worldwide, with a five-year survival rate below 20%. Ferroptosis—a regulated form of cell death driven by iron-dependent lipid peroxidation—has emerged as a promising therapeutic strategy, yet its regulation in ESCC remains poorly understood. We investigated the role of tripartite motif-containing 31 (TRIM31), an E3 ubiquitin ligase, in ESCC progression and ferroptosis.Results:TRIM31 expression was significantly elevated in ESCC tissues compared with normal esophageal tissues (The Cancer Genome Atlas and Genotype-Tissue Expression datasets; p < 0.001) and correlated with advanced Tumor, Node, and Metastasis (TNM) stage (p = 0.004), lymph node metastasis (p = 0.024), and poor overall survival (p = 0.0027). Functional assays revealed that TRIM31 knockdown reduced ESCC cell proliferation, impaired colony formation, and suppressed migration (p < 0.01). In vivo, TRIM31 silencing decreased xenograft tumor volume by over 70% and Ki-67 expression by 73%. Mechanistically, TRIM31 directly interacted with VDAC1 via its coiled-coil domain, promoting VDAC1 ubiquitination and proteasomal degradation. This interaction inhibited ferroptosis, as evidenced by increased lipid reactive oxygen species, elevated intracellular Fe2+ levels, and mitochondrial damage upon TRIM31 knockdown. Conversely, TRIM31 overexpression attenuated ferroptosis induced by RSL3. We further identified hepatocyte nuclear factor 4 alpha as a transcriptional activator of TRIM31, binding to its promoter region. Importantly, TRIM31 knockdown synergized with the ferroptosis inducer imidazole ketone erastin, achieving a 90% reduction in tumor growth without significant toxicity.Conclusion:TRIM31 promotes ESCC progression by degrading VDAC1 and suppressing ferroptosis. Targeting TRIM31 enhances ferroptosis-based therapy and represents a novel, clinically actionable strategy for ESCC treatment. Antioxid. Redox Signal. 00, 000–000.
✓ 已验证
DOI
高影响因子
Cell Host & Microbe
·
2026
·
IF 18.7
Siyuan Fan,Xinyue Cai,Weiqi Wang,Meiling Wu,Xiaoyao Huang,Feng Ding,Hao Guo,Geng Dou,Haotian Luo,Shuai Shao,Jing Guo,Zhenlai Zhu,Peisheng Liu,Linfeng Cheng,Siying Liu,Zihan Li,Kun Xuan,Shiyu Liu
Ultraviolet irradiation, particularly ultraviolet B (UVB), damages keratinocytes, potentially causing actinic cheilitis. Commensal bacteria help maintain barrier function and protect the host. However, it is unclear if commensal bacteria can protect the host from UVB irradiation. Here, we demonstrate that Rothia mucilaginosa ( R. mucilaginosa )-derived membrane vesicles (RMVs) contain ferrochelatase, which stabilizes labile iron in host cells to alleviate UVB-induced ferroptosis. We demonstrate that R. mucilaginosa abundance on lip vermilion inversely correlates with actinic cheilitis severity in patients. Mechanistically, we find that UVB induces R. mucilaginosa to release RMVs, which are internalized by host cell lysosomes. The ferrochelatase contained within these RMVs catalyzes conversion of Fe 2+ and porphyrin into heme, thereby alleviating UVB-induced iron overload and ferroptosis. Topical application of RMVs relieves actinic cheilitis in patients (ChiCTR, no. ChiCTR2500100015). Collectively, we reveal an iron stabilization mechanism through which commensal bacteria protect the host against UVB and expand our understanding of the relationship between commensal bacteria and hosts.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2026
·
IF 6.1
Dong Fan,Zongming Wang,Shixue Luo,Xuanhao Huang,Xingyi Yuan,Yanan Wang,Zhongyu Wang,Huitong Chen,Weiwen Wang,Yuxin Ma,Chang Zhou,Xiaobao Jin,Jing Liu,Xin Wang
Background: Nonfunctioning pituitary adenoma (NFPA) is among the most prevalent intracranial tumors. As surgical resection remains the primary treatment, there is a need for new therapeutic strategies. Plumbagin (PLB), a bioactive naphthoquinone compound derived from the roots of Plumbaginaceae Juss, has been used in anti-tumor research in recent years, but its mechanism remains controversial.Purpose: The aim of this study was to explore the molecular mechanism of PLB-induced ferroptosis in NFPA.Methods: The cell viability of PLB against PDFS cells was first assessed by CCK-8, colony formation, and EDU assays. Network pharmacology, molecular docking, and molecular dynamics were then used to screen out targets associated with ferroptosis. Finally, the Nrf2/FTH1 pathway was validated by a 3D multicellular tumour spheroids (MCTSs) model, q-PCR, and Western blot in vitro and in vivo.Results: Compared to temozolomide (TMZ), PLB more potently inhibited the viability of PDFS cells. In vitro, PLB treatment was associated with downregulation of the Nrf2/FTH1 pathway, accompanied by increased lipid peroxidation and labile iron pool (LIP) accumulation. Furthermore, PLB treatment led to the upregulation of NCOA4 and an increase in intracellular free iron, consistent with ferritinophagy activation. These effects collectively point to the induction of ferroptosis.Conclusion: This study demonstrates that PLB may induce ferroptosis in PDFS cells. The mechanism involves suppression of the Nrf2/FTH1 pathway, subsequent upregulation of NCOA4, and ferritinophagy-driven iron overload. These results identify PLB as a potential ferroptosis inducer and warrant further investigation into its therapeutic potential for NFPA. The image shows a biochemical pathway illustrating ferritinophagy and ferroptosis. Iron in the form of Fe superscript 3 is transported by transferrin into the cell, where it is stored in ferritin. Ferritin is directed to the autolysosome, facilitated by Lamp2, where iron is released as Fe superscript 2. NCOA4 and LC3 are involved in ferritinophagy, leading to the labile iron pool. The Fenton reaction produces reactive oxygen species, contributing to ferroptosis. Nrf2 regulates FTH1, with arrows indicating promotion and inhibition. Plumbagin is shown affecting the pathway, with an illustration of a mouse receiving an injection, highlighting the interaction between NCOA4, FTH1 and Nrf2 in the brain. Arrows indicate promotion and inhibition effects within the pathway.Diagram of ferritinophagy and ferroptosis: iron regulation, NCOA4, FTH1, Nrf2 and plumbagin effects.
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2026
·
IF 11
Jiarong Liang,Si Wang,Zhonghui Ma,Fei Kuang,Xiangkun Li,Zhilong Gong,Jinzhu Su,Zhiyi Wang
Combining efficient photocatalytic activity with precise targeting is crucial for covalent organic framework (COF)-based nanomedicines to remodel the immunosuppressive microenvironment and sensitize “cold” tumors to immunotherapy. Herein, we constructed two isomorphic frameworks featuring distinct electronic topologies: a zwitterionic squaric acid (SA) COF with inherent electrostatic asymmetry, and a charge-neutral terephthaldehyde (TA) COF. The spatial divergence of ion centers in SA COF triggers intense molecular-level ionic displacement polarization, creating a robust internal electric field. Such unique field-effect regulation accelerates photogenerated charge separation for efficient superoxide anion production, enhances intersystem crossing for singlet oxygen generation, and promotes nonradiative energy relaxation for high-performance photothermal conversion under dual-wavelength irradiation. After PEGylation and iRGD modification, the formulated SA@PEG-iRGD exhibits excellent physiological stability and active deep tumor penetration. With near-infrared absorption, it enables high-contrast photoacoustic imaging for guided dual-wavelength (660/808 nm) phototherapy. This spatiotemporally controlled therapeutic cascade triggers lethal ferroptosis and precise photothermal ablation, potently activating immunogenic cell death. Combined with aPD-L1 therapy, it eliminates primary tumors, produces abscopal effects, and establishes immune memory against recurrence and metastasis. This study highlights the value of electronic structure engineering in COF-based precision nanomedicine.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Jie Yang,Xue Wen,Yi-Tong Fu,Chao Li,Hai-Long Chang,Yao-Yao Lu,Xue-Ru Li,Rui-Feng Fan
Perfluorooctanoic acid (PFOA), a persistent organic pollutant, is widely distributed in the environment, leading to substantial bioaccumulation and posing significant public health concerns. The kidney is the primary target organ for PFOA, but a recognized mechanism remains unclear. The chicken embryo has been widely used as a maternal-independent model in toxicity studies. However, the toxic effects of PFOA in chicken embryo kidneys remain limited. In the present study, chicken embryos were injected with PFOA of different concentrations through the air cell to establish an in vivo model, and establish an in vitro model of chicken embryo kidney (CEK) cells for PFOA exposure. The results showed that PFOA promoted nephrotoxicity and induced ferroptosis in chicken embryo kidneys. Meanwhile, ferroptosis occurred in PFOA-treated CEK cells and was alleviated by ferroptosis inhibitor Ferrostatin-1 (Fer-1), Deferoxamine (DFO), and autophagy inhibitor Chloroquine (CQ). Further results suggested that PFOA activated nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in chicken embryo kidneys and CEK cells. Mechanistically, PFOA diminished NCOA4 ubiquitination by reducing the expression of HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2), leading to increased NCOA4 expression and activated ferritinophagy. These findings indicated that PFOA induced ferroptosis via HERC2-regulated NCOA4 ubiquitination-dependent degradation in chicken embryo kidneys.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ORAL DISEASES
·
2024
·
IF 2.9
Huiwen Chen,Yining Zhou,Yingli Liu,Wei Zhou,Lina Xu,Dihua Shang,Jing Ni,Zhongchen Song
Objectives The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients. Materials and Methods Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation. Results Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS. Conclusions IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.
研究领域:
牙科学
·
肾病学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2026
·
IF 10.2
Pengyu Wang,Xia Zhang,Ning Ding,Aimei Liu,Shuo Zhang,Yan Song,Leiming Yang,Huiting He,Mi Chen,Xiying Guo,Youzhi Zhang
Trimethyltin chloride (TMT), a poison from water and soil, has been linked to bradycardia. Ferroptosis, an iron-driven type of regulated cell death, is critically involved in cardiovascular diseases. However, the mechanism of TMT-induced myocardial injury remains unclear. This study aims to investigate the toxicological mechanism of TMT-induced myocardial injury and evaluate the protective effect of Lut. In this study , RNA sequencing identified Gpx4 as the key ferroptosis-related gene of TMT-induced cardiomyopathy. In vitro , TMT induced ferroptosis, which was reversed by Ferrostatin-1. Notably, TMT also suppressed mitophagy, co-treatment with chloroquine (CQ) aggravated TMT-induced ferroptosis, whereas Urothione A reversed this effect. In vivo and in vitro , TMT caused bradycardia and myocardial ferroptosis, while Luteolin (Lut) exerted anti-ferroptosis effects. Furthermore, TMT increased DRP1 phosphorylation and reduced the expression of mitochondrial fusion and mitophagy proteins, which were restored by Lut. And the anti-ferroptosis effect of Luteolin was abolished by CQ. Collectively, it revealed that TMT induced ferroptosis in vitro and vivo, while Lut alleviated TMT-induced myocardial injury by activating mitophagy, inhibiting ferroptosis, then restoring mitochondrial function.
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Tiantian Chen,Yan Qin,Yao Li,Yaru Li,Jiajia Luo,Lanlan Fan,Meiyu Feng,Zheng Wang,Yanjun Zhao
The dose-dependent cardiomyopathy of adriamycin (doxorubicin) limits its long-term clinical use, which is revealed as a consequence of cardiomyocyte ferroptosis. As a ferrous iron (Fe 2 + )-dependent regulated cell death pathway, ferroptosis is induced by the tailored lipid peroxides in the cell membranes. Herein, iron-chelating polymer micelles are reported for concurrent doxorubicin delivery and cardiotoxicity reduction. The amphiphilic polymer consists of methoxy poly (ethylene glycol)- co -poly (glutamic acid) copolymer as the backbone and deferiprone analog as the side chain. The chiral polymer adopted the α-helix conformation to enable prolonged retention in the cell membranes, resulting in efficient iron chelation, ferroptosis inhibition, and cardiotoxicity reduction. The co-encapsulation of doxorubicin and coenzyme Q 10 (CoQ 10 ) in micelles further alleviates the cardiotoxicity because the reduced CoQ 10 can act as a radical trapping agent to constrain lipid peroxidation and cardiomyocyte ferroptosis. The reduction of cardiotoxicity is accompanied by enhanced anticancer efficacy in an in vivo murine breast cancer model. The chiral iron-chelating polymer micelles can be a promising platform for enhanced doxorubicin delivery and reduced cardiac adverse effects.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2023
·
IF 3.3
Xiuli Liu,Guilan Li,Shaoxiong Chen,Huiyun Jin,Xiaodong Liu,Linfang Zhang,Zhaohui Zhang
Beryllium sulfate (BeSO 4 ) can result to lung injuries, such as leading to lipid peroxidation and autophagy, and the treatment of beryllium disease has not been well improved. Ferroptosis is a regulated cell death process driven by iron-dependent and lipid peroxidation, while ferritinophagy is a process mediated by nuclear receptor coactivator 4 (NCOA4), combined with ferritin heavy chain 1 (FTH1) degradation and release Fe 2+ , which regulated intracellular iron metabolism and ferroptosis. Hydrogen sulfide (H 2 S) has the effects of antioxidant, antiautophagy, and antiferroptosis. This study aimed to investigate the effect of H 2 S on BeSO 4 -induced ferroptosis and ferritinophagy in 16HBE cells and the underlying mechanism. In this study, BeSO 4 -induced 16HBE cell injury model was established based on cellular level and pretreated with deferoxamine (DFO, a ferroptosis inhibitor), sodium hydrosulfide (NaHS, a H 2 S donor), or NCOA4 siRNA and, subsequently, performed to detect the levels of lipid peroxidation and Fe 2+ and the biomarkers of ferroptosis and ferritinophagy. More importantly, our research found that DFO, NaHS, or NCOA4 siRNA alleviated BeSO 4 -induced ferroptosis and ferritinophagy by decreasing the accumulation of Fe 2+ and lipid peroxides. Furthermore, the relationship between ferroptosis, ferritinophagy, H 2 S, and beryllium disease is not well defined; therefore, our research is innovative. Overall, our results provided a new theoretical basis for the prevention and treatment of beryllium disease and suggested that the application of H 2 S, blocking ferroptosis, and ferritinophagy may be a potential therapeutic direction for the prevention and treatment of beryllium disease.
✓ 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）