COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Hailun Zheng,Xiaoyan Mao,Zhiwei Chen,Linying Wang,Fuxiang Shangguan,Zihao Tao,Jinyao Ye,Weilan Cao,Qing Yao,Lili Yan,Ruijie Chen,Shihui Bao,Longfa Kou
Chemotherapy remains one of the main treatments for gastric cancer, but the efficacy of 5-fluorouracil (5-FU) is limited by drug resistance. Ferroptosis is a unique mode of regulated cell death characterized by iron accumulation and lipid peroxidation, and its induction by aberrant STAT3 signaling may contribute to chemotherapy resistance. Cryptotanshinone (Cpt) is a bioactive compound extracted from Salvia miltiorrhiza that acts as a STAT3 inhibitor and has shown efficacy against several malignancies, endowing its potential as an agent to overcome the chemotherapy of gastric cancer. Importantly, cancer cells—especially drug-resistant cells—often upregulate amino acid transporters to import indispensable nutrients that support rapid proliferation, and therefore these transporters could guide the target delivery of chemotherapeutics for enhanced delivery efficiency. Here, we developed an amino acid transporter-targeted nanoplatform (F/C@Trp-NPs) co-loaded with 5-FU and Cpt to target the SLC6A14 (ATB 0,+ ) transporter, which is abnormally upregulated in gastric cancer cells, and evaluated its anticancer effects. The F/C@Trp-NPs significantly inhibited gastric cancer cell proliferation in vitro, consistent with the in vivo results. This study provides a promising new therapeutic strategy for gastric cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2019
·
IF 2.705
Ning Wang,Guang-Zhi Zeng,Jun-Lin Yin,Zhao-Xiang Bian
Currently, there is no effective treatment for Burkitt's lymphoma in patients aged above 60 years, and thus research on effective treatment options for Burkitt's lymphoma has been gaining increasing attention. Artesunate has been identified as a novel effective growth suppressor in Burkitt's lymphoma. Here, we utilized molecular biology , transcriptome analysis , and other techniques to study artesunate-induced death of the Burkitt's lymphoma cells DAUDI and CA-46, the effect of artesunate on gene expression in DAUDI and CA-46 cells, and the effect of artesunate-induced ATF4-CHOP-CHAC1 pathway on ferroptosis . We also studied the inhibitory effects and ferroptosis induction of artesunate on CA-46 cells in mouse xenografts. Results showed that artesunate induced ferroptosis in DAUDI and CA-46 cells, as evidenced by the protective effect of liproxstatin-1, ferrostatin-1, and desferoxamine, resulting in an endoplasmic reticulum stress response, a ctivation of the ATF4-CHOP-CHAC1 pathway enhanced ferroptosis in DAUDI and CA-46 cells. A mouse-transplanted tumor model showed that artesunate can inhibit the proliferation and induce ferroptosis of CA-46 cells in vivo . This study provides a novel perspective for the development of drugs against different types of Burkitt's lymphomas.
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2025
·
IF 15.7
Jin Chengkang,Xu Xiaoling,Yao Ning,Zhang Hairui,Chen Changjiang,Zeng Lingyao,Liu Zhiyun,Lei Lanjie,Cui Shumao,Wen Chengping,Shi Liyun
Accumulation of senescent cells is associated with aging and age-related diseases. However, current clearance therapies targeting senescent cells are often limited by low efficiency, poor specificity, and insufficient penetration. Here we develop a nano-platform composed of a probe (GD) that can be specifically activated by senescent cells, a photosensitizer (Ce6), and a peptide (HK) for targeting ferritin, named HK-PCGC. We show that upon entering senescent cells, GD is activated by high levels of β-galactosidase, releasing fluorescence to excite Ce6. Ce6 then generates reactive oxygen species to eliminate these cells. Additionally, we find that under the guidance of the peptide HK, our system degrades ferritin to trigger ferroptosis, further eliminating senescent cells. Collectively, we demonstrate that HK-PCGC can effectively eliminate senescent cells, reduce the senescence-associated secretory phenotype, and safely improve the physical fitness of aged mice. This study integrates senescent cell responsiveness, laser-free photodynamic therapy, and induction of ferroptosis, offering a potential approach for delaying aging.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2025
·Vol. 15
·期 1
·32
·
IF 6.6
Xiaoping Guo,Chao Wang,Xin Yu,Shanshan Zhang,Haoyu Zheng,Tianqi Liu,Zhili Chen,Guoqiang Wang,Fang Wang
Recently, extreme weather has been regarded as a risk factor for exacerbating allergic airway inflammation (AAI), but its underlying mechanism remains unclear. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been implicated in various lung diseases. This study investigated whether cold exposure aggravated OVA-induced AAI by promoting ferroptosis. A murine AA model was established using OVA sensitization and challenge. Mice were exposed to cold temperatures (10 °C or 4 °C) for 4 h daily. Ferroptosis was assessed by measuring ferroptosis-related markers (GPX4, ACSL4, FTL), iron deposition (Alcian Blue-Periodic Acid-Schiff Staining), lipid peroxidation (MDA), antioxidant levels (GSH), and mitochondrial ultrastructure (TEM). The ferroptosis inhibitor ferrostatin-1 (Fer-1) was administered to evaluate its protective effects. Airway inflammation, lung function, and histopathology were also analyzed. Cold exposure significantly worsened AA symptoms, including increased Th2 cytokine levels (IL-4, IL-5, IL-13, IL-33), impaired lung function, and enhanced airway remodeling and mucus production. These effects were more pronounced at 4 °C. Cold exposure also induced ferroptosis, as evidenced by decreased GPX4 and FTL, increased ACSL4, elevated iron and MDA levels, reduced GSH, and mitochondrial damage. Treatment with Fer-1 mitigated these changes, alleviating inflammation, improving lung function, and reducing histological damage. Cold exposure exacerbated AAI by inducing ferroptosis in lung tissues. Inhibition of ferroptosis with Fer-1 attenuated these aggravation effects, suggesting ferroptosis as a potential mechanistic link between cold exposure and AAI severity. Targeting ferroptosis might offer a novel therapeutic strategy for mitigating AAI under cold conditions.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
·
2025
·
IF 7.4
Yunhong Zhang,Zhen Zhang,Xinkui Liu,Chu Chu,Xiaoyan Yu,Qiaoqiao Han,Wei Li,Tingting Zhang,Huiyan Zu,Nannan Fan,Ran Wei,Feifei Shi,Fang Li,Fei Xu,Bin Wang,Xia Li
BACKGROUND:Deep vein thrombosis (DVT) is a prevalent peripheral vascular disorder associated with abnormal epigenetic processes and altered gene expression in endothelial cells. Accumulating evidence has demonstrated that NAT10 (N-acetyltransferase 10)–mediated N4-acetylcytidine modification exerts unique roles in ferroptosis, but its roles are still elusive in DVT.METHODS:To explore the potential mechanism of NAT10 and ferroptosis on thrombogenesis, we used NAT10 and GPX4 (glutathione peroxidase 4) knockout mice as an in vivo model, and utilized techniques, such as RNA immunoprecipitation, acRIP-qPCR, N4-acetylcytidine Dot Blotting assay, and Western blotting, for detailed molecular analysis.RESULTS:GPX4 is a pivotal gene that suppresses ferroptosis. Utilizing endothelial cell–specific GPX4 conditional knockout mice (GPX4fl/flCdh5-Cre+), we proved that ferroptosis in endothelial cells promotes the formation of thrombosis. Previous evidence indicates that NAT10 overexpression induces ferroptosis and downregulates GPX4 expression. Here, we found that NAT10 expression was elevated in DVT mice, and silencing of NAT10 markedly attenuated ferroptosis both in vitro and in vivo. Furthermore, endothelial cell–specific knockout of NAT10 (NAT10fl/flCdh5-Cre+) demonstrated a reduction in endothelial ferroptosis, thereby inhibiting both the formation and progression of DVT. Mechanistic studies indicated that NAT10 facilitated the N4-acetylcytidine modification of HMOX1 (heme oxygenase 1), which enhanced its mRNA stability, leading to the accumulation of ferrous ions, and exacerbating endothelial dysfunction in DVT.CONCLUSIONS:Collectively, our data elucidate that downregulation of NAT10 mitigates endothelial ferroptosis and prevents DVT formation and progression by modulating HMOX1 expression, which offers a potential novel strategy for the prevention and treatment of thrombosis in DVT.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·
IF 12.6
Hu Zhihao,Li Hongji,Gan Kai,Li Yu,Jiang Yao,Zhang Keying,Li Zhengxuan,Zhou Yike,Lu Tong,Xu Chao,Liu Shaojie,He Limin,Yang Fa,Jiang Jun,Song Hongtao,Wang Ying,Guo Li,Shi Changhong,Wen Weihong,Han Donghui,Qin Weijun
Radioresistance and off-target toxicity remain major challenges in prostate cancer (PCa) radiotherapy. Here, we report a biomimetic nanoplatform (Au/MOF-FIN@M-gy1) that synergistically enhances radiation deposition and ferroptosis for precision radiosensitization. By engineering macrophage membranes with prostate-specific membrane antigen (PSMA)-targeting nanobodies (gy1), we achieve tumor-selective delivery of Au/MOF nanoparticles preloaded with ferroptosis inducers (FINs). Upon lysosomal release, FINs disrupt redox homeostasis via GPX4 suppression, while Au/MOF amplifies radiation-induced reactive oxygen species (ROS), collectively triggering lethal lipid peroxidation cascades. This dual mechanism is further demonstrated to elicit radiosensitizing effects in both bone-metastatic and radio-refractory PCa models without requiring radiation dose escalation, thereby improving the therapeutic index. Our study demonstrates a nanoparticle-enabled strategy to enhance tumor-specific radiotherapy by dual-targeting metabolic vulnerabilities.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2025
·
IF 6.9
Jie Li,Qihui Zhu,Yang Li,Haiyu Zhao,Yi Bi,Chuanying Pan,Min Wang,Lin Han,Xianyong Lan
Phloretin, a plant-derived dihydrochalcone bioactive compound, potentially modulates preadipocyte differentiation, although this remains controversial and requires further clarification. To clarify this point, herein, phloretin gavage inhibited mice obesity, reduced adipocyte size, and ameliorated serum lipid parameters, including triglycerides. In vitro, phloretin suppressed the differentiation of 3T3-L1 and bovine preadipocytes, decreasing lipid droplet content and reducing CEBPα and PPARγ levels. Moreover, during differentiation, glutathione peroxidase (GSH-Px) ultimately decreased with elevations in malondialdehyde (MDA) and Fe 2+ levels, along with acyl-CoA synthetase long-chain family member 4 ( ACSL4 ), P53 , and SLC7A11 expression, indicating differentiation occurring under mild oxidation and slight ferroptosis activation. Similar to (1 S ,3 R )-RSL3, phloretin further stimulated the ferroptosis pathway by inhibiting glutathione reductase (GR) and GSH-Px, increasing the content of MDA and Fe 2+ . Simultaneously, the suppression of Fth1 , Slc7a11 , and Sod2 transcription, significantly elevated HMGB1 protein, and markedly downregulated glutathione peroxidase 4 (GPX4) and TFR protein collectively confirmed that phloretin activated the ferroptosis signaling pathway to inhibit differentiation. Further phosphoproteomic analysis identified dm-phosphorylation sites (p-eEF2K[S365], p-AMPKα1[S491], and p-CaMKK2[S495]) enriched in AMPK/MAPK signaling pathways and transferrin receptor binding. Further molecular docking simulations revealed that phloretin binds to PPARγ or transferrin to activate ferroptosis pathway, revealing the potential crosstalk between ferroptosis signaling pathway and adipogenic differentiation processes.
✓ 已验证
产品关联
DOI
高影响因子
Cell Reports Medicine
·
2025
·
IF 10.6
Jin Lei,Xinxin Sun,Jianbin Shi,Pengfei Wang,Qingyue Guan,Zhixiao Zhang,Zhonggui He,Jin Sun,Peng Huang,Jing Lin,Cong Luo,Shenwu Zhang
Ferroptosis is recognized as a form of regulated cell death characterized by iron-dependent lipid peroxidation and significant immunogenic properties. However, we observe that the hypoxic tumor microenvironment (TME) of solid tumors severely limits ferroptosis induction and antitumor immune responses, while simultaneously promoting programmed death-ligand 1 (PD-L1) expression, thereby further compromising tumor immunotherapy. Herein, we exploit a fluorinated prodrug-engineered nano-remodeler to reverse the hypoxic and immunosuppressive TME for enhancing ferroptosis/immunomodulation-driven antitumor therapy. The nano-remodeler is elaborately co-assembled by the disulfide-bonded fluorinated JQ1 prodrug (a PD-L1 inhibitor) and sorafenib (Sor, a ferroptosis inducer). As expected, the ferroptosis induction efficiency and antitumor immunogenicity of Sor are significantly improved due to oxygen supply in hypoxic solid tumors, resulting in a highly synergistic ferroptosis-immunotherapy with JQ1. As a result, this nano-remodeler exerts a potent tumor inhibitory effect in multiple tumor models. This study provides insights into the nanotherapeutic paradigm of tumor hypoxia intervention in multimodal ferroptosis-immunotherapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Xiaowei Yang,Guangduo Zhu,Ming Li,Haibo Zhan,Feng Wang
Ferroptosis is an important pathological factor in sepsis-induced cardiomyopathy (SIC). Zinc finger protein 36 (ZFP36) is an RNA-binding protein regulating cellular biological processes by degrading target genes. Studies have shown that ZFP36 is highly associated with ferroptosis. BALB/c mice were administered lipopolysaccharide (LPS) intraperitoneally to establish an SIC model. After LPS exposure for 24 h, mice showed myocardial damage and ferroptosis, and an elevated protein level of ZFP36 was detected in the myocardium. H9c2 cells were transfected with plasmid-carrying short hairpin RNA to knock down ZFP36. The mRNA-sequencing data suggested that ZFP36 may be involved in the ferroptosis process of SIC. After inhibiting ZFP36 expression, H9c2 cell viability was reduced, and we detected an increase in lipid peroxides by C11-BODIPY581/591. ZFP36 knockdown intensified LPS-induced ferroptosis and cell injury. ZFP36 expression was inhibited in mice by recombination adeno-associated virus 9-containing shRNA. SIC mice with ZFP36 knockdown showed left ventricular systolic dysfunction aggravatingly. In SIC mice with ZFP36 knockdown, disruption of myocardial structure and increased immunological infiltration. After ZFP36 downregulation, the SIC hearts displayed massive 4-HNE and malondialdehyde accumulation, decreased glutathione content and superoxide dismutase activity, and elevated iron-positive myocardium by Prussian blue staining. The alteration of ferroptosis markers evidenced the activation of ferroptosis in ZFP36-deficient SIC mice. In addition, we observed that the level of solute carrier family 7 member 11 was downregulated after the ZFP36 knockdown both in vivo and in vitro . In conclusion, deficiency of ZFP36 exacerbates SIC by activating ferroptosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Haijie Wang,Qian An,Wenxin Wang,Hao Zhou,Youping Deng,Yu-Qi Feng,Wei-Hai Chen,Zhenwei Wei,Xiangyu Wang
Emerging evidence has linked ferroptosis to major chronic diseases such as neurodegenerative and cardio-vascular disorders. Understanding the early stage metabolic network during ferroptosis is essential for uncovering disease mechanisms and developing therapeutic strategies. As oxidative stress occurs in the early phase of ferroptosis, me-tabolites bearing thiol, amino, and unsaturated carboxyl groups may undergo significant changes. However, their comprehensive profiling remains challenging. Here, we developed a boron beacon–based magnetic chemoselective probe for the targeted enrichment, labeling, and simultaneous mass spectrometric analysis of carboxyl-, amino-, and thiol-containing metabolites in complex biological environments. Compared to conventional probes, our design offers significantly faster reaction kinetics, higher labeling efficiency, and a streamlined workflow. Moreover, the boron-based probes generate distinct isotopic patterns in MS1 and diagnostic fragments in MS2 spectra, enabling precise submetabolome targeting and characterization. Using this strategy, we performed submetabolome profiling of HeLa cells undergoing ferroptosis and identified 303 dysregulated metabolites. The results revealed coordinated perturbations in key metabolic pathways, including transsulfuration, fatty acid biosynthesis, and glutathione metabolism. This work not only provides mechanistic insights into ferroptosis regulation but also establishes a high-throughput and functionally guided platform for metabolomic network analysis for future studies.
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 3
·674
·
IF 3.267
Jie Liu,Xican Li,Rongxin Cai,Ziwei Ren,Aizhen Zhang,Fangdan Deng,Dongfeng Chen
To elucidate the mechanism of anti-ferroptosis and examine structural optimization in natural phenolics, cellular and chemical assays were performed with 2′-hydroxy chalcone butein and dihydroflavone (S)-butin. C11-BODIPY staining and flow cytometric assays suggest that butein more effectively inhibits ferroptosis in erastin-treated bone marrow-derived mesenchymal stem cells than (S)-butin. Butein also exhibited higher antioxidant percentages than (S)-butin in five antioxidant assays: linoleic acid emulsion assay, Fe3+-reducing antioxidant power assay, Cu2+-reducing antioxidant power assay, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-trapping assay, and α,α-diphenyl-β-picrylhydrazyl radical (DPPH•)-trapping assay. Their reaction products with DPPH•were further analyzed using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Butein and (S)-butin produced a butein 5,5-dimer (m/z542, 271, 253, 225, 135, and 91) and a (S)-butin 5′,5′-dimer (m/z542, 389, 269, 253, and 151), respectively. Interestingly, butein forms a cross dimer with (S)-butin (m/z542, 523, 433, 419, 415, 406, and 375). Therefore, we conclude that butein and (S)-butin exert anti-ferroptotic action via an antioxidant pathway (especially the hydrogen atom transfer pathway). Following this pathway, butein and (S)-butin yield both self-dimers and cross dimers. Butein displays superior antioxidant or anti-ferroptosis action to (S)-butin. This can be attributed the decrease in π-π conjugation in butein due to saturation of its α,β-double bond and loss of its 2′-hydroxy group upon biocatalytical isomerization.Keywords:butein;(S)-butin;anti-ferroptosis;antioxidant;2′-hydroxy chalcone;isomerization
✓ 已验证
DOI
PubMed
高影响因子
Nanotoxicology
·
2023
·
IF 5
Xue Zhang,Fei Kong,Tian Wang,Xin Huang,Wanqing Li,Meichen Zhang,Tao Wen,Jian Liu,Yu Zhang,Jie Meng,Haiyan Xu
Iron oxide nanoparticles (IONPs) are mostly intended to be administrated intravenously, understanding the interaction of IONPs with vascular endothelial cells is extremely crucial for developing safe application regimes of IONPs. In this work, interactions of three kinds of IONPs to endothelial cells were investigated both in human umbilical vein endothelial cells (HUVECs) and in healthy mice. Both meso-2,3-dimercaptosuccinic acid (DMSA) coated Fe3O4 NPs (DMSA-Fe3O4 NPs) and DMSA-Fe2O3 NPs induced cell growth inhibition, while polyglucose sorbitol carboxymethyether coated Fe2O3 NPs(PSC-Fe2O3 NPs) did not. The PSC coating inhibited the cellular uptake of the IONPs. Both DMSA-Fe3O4 and DMSA-Fe2O3 NPs induced ferroptosis of HUVEC through upregulating phospholipid peroxides, which could be inhibited by typical ferroptosis inhibitors ferrostatin-1, Trolox and deferoxamine. Moreover, transforming growth factor beta 1 (TGFβ1) was upregulated by DMSA-Fe3O4 NPs at protein and gene level. The inhibitor of TGFβ1 receptor LY210 could reduce the effect. When being intravenously injected in mice, DMSA-Fe3O4 NPs were observed locating in the liver, increased the levels of lipid peroxidation (4-hydroxynonenal), acyl-CoA synthetase long-chain family member 4(ACSL4) and TGFβ1, indicating ferroptosis occurrence in vivo. The ferroptosis of vascular endothelial cells in exposure with IONPs depended on the surface coating and core chemistry of the NPs. Both DMSA-Fe3O4 NPs and DMSA-Fe2O3 NPs could induce the ferroptosis of endothelial cells, while PSC-Fe2O3 NPs did not induce ferroptosis and apoptosis possibly due to the very low cellular uptake. DMSA-Fe3O4 NPs and TGFβ1 formed feedforward loop to induce ferroptosis.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）