MOLECULAR PLANT PATHOLOGY
·
2024
·Vol. 25
·期 7
·e13489
·
IF 4.8
Qiao Liu,Ruhui Long,Chaoxiang Lin,Xinping Bi,Zhibin Liang,Yi Zhen Deng
A cell death pathway, ferroptosis, occurs in conidial cells and is critical for formation and function of the infection structure, the appressorium, in the rice blast fungus Magnaporthe oryzae . In this study, we identified an orthologous lysophosphatidic acid acyltransferase (Lpaat) acting at upstream of phosphatidylethanolamines (PEs) biosynthesis and which is required for such fungal ferroptosis and pathogenicity. Two PE species, DOPE and SLPE, that depend on Lpaat function for production were sufficient for induction of lipid peroxidation and the consequent ferroptosis, thus positively regulating fungal pathogenicity. On the other hand, both DOPE and SLPE positively regulated autophagy. Loss of the LPAAT gene led to a decrease in the lipidated form of the autophagy protein Atg8, which is probably responsible for the autophagy defect of the lpaat Δ mutant. GFP-Lpaat was mostly localized on the membrane of lipid droplets (LDs) that were stained by the fluorescent dye monodansylpentane (MDH), suggesting that LDs serve as a source of lipids for membrane PE biosynthesis and probably as a membrane source of autophagosome. Overall, our results reveal novel intracellular membrane-bound organelle dynamics based on Lpaat-mediated lipid metabolism, providing a temporal and spatial link of ferroptosis and autophagy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Bin Zhao,Mengying Wei,Xiaomeng Zhou,Wenfeng Liu,Qiang Li,Yumeng Xue,Li-Li Tan,Li Shang
Hypertrophic scar (HS) remains a major challenge for clinicians due to unsatisfactory therapeutic performance. Although inducing apoptosis of HS fibroblasts (HSFs) has proved to be an effective nonsurgical treatment strategy, potential chemotherapy resistance to apoptosis of HSFs makes the development of new and efficient strategies highly demanding. Herein, a ferroptosis-apoptosis combined therapeutic strategy for the treatment of HS is developed through supramolecular self-assembly between cucurbit[7]uril (CB[7]) and two bioactive agents, dihydroartemisinin (DHA) and gold nanoclusters (AuNCs). The resulting self-assembled supramolecular nanoparticles, named CAD NPs, showed high guest loading efficiency and prominent pH-responsive degradability in the acidic lysosomes of HSFs. Importantly, both DHA and AuNCs act synergistically to generate excessive reactive oxygen species and lipid peroxidation, leading to mitochondrial damage, and ultimately inducing concurrent ferroptosis and apoptosis on HSFs. Upon further loading into hydrogel microneedles to facilitate their transdermal delivery, these CAD NPs showed superior antiscar therapeutic effects in shortening the treatment span to 3 weeks and improving the HS appearance, as demonstrated at a rabbit ear model of HS. The present supramolecular assembly-based ferroptosis-apoptosis strategy provides an innovative guideline for efficiently treating HS as well as other diseases.
✓ 已验证
产品关联
DOI
高影响因子
RENAL FAILURE
·
2025
·
IF 3
Ningjun Shao,Kedan Cai,Yue Hong,Lingping Wu,Qun Luo
Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates many critical genes associated with iron storage and transportation, the activity of which is influenced by E3 ligase-mediated ubiquitination. We wondered whether there is a deubiquitinase that mediates the deubiquitination of Nrf2 to stabilize Nrf2 expression and further prevent diabetic kidney disease (DKD). High glucose (HG) was applied to induce an in vitro model of DKD. The effects of HG on HK-2 cell viability, apoptosis, Fe2+ level, Nrf2, and ubiquitin-specific protease 9X (USP9X) were assessed by cell counting kit-8 (CCK-8) assay, flow cytometry, iron assay, and Western blot. The direct interaction between Nrf2 and USP9X was analyzed using co-immunoprecipitation and ubiquitination assay. After transfection and ferrostatin-1 (Fer-1) intervention, Nrf2 and USP9X levels, cell viability, apoptosis, and Fe2+ level were tested again. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) contents, and ferroptosis-related markers were assessed by ROS assay kit, ELISA, and Western blot. HG reduced cell viability and levels of USP9X and Nrf2, while elevating apoptosis and Fe2+ level. An interaction between USP9X and Nrf2 has been verified and USP9X deubiquitinated Nrf2. Nrf2 up-regulation augmented the viability, GSH content, and ferroptosis-related protein expressions, while suppressing the apoptosis, Fe2+ level, MDA, and ROS content in HG-mediated HK-2 cells, which was reversed by USP9X silencing. Fer-1 offset the combined modulation of Nrf2 and siUSP9X on HG-induced HK-2 cells. USP9X mediates Nrf2 deubiquitinase to hamper the ferroptosis in DKD in vitro.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
You Zhou,You Wu,Rui Zhu
Background Septic acute kidney injury (S-AKI) is a major cause of acute kidney injury (AKI), but no effective therapies exist to prevent or treat it. Although KLF6 is linked to various pathophysiological processes, its exact role in S-AKI is not yet fully understood. Methods The role of KLF was investigated using both the mouse CLP model and in vitro systems. To identify the transcriptional targets regulated by KLF6, ChIP-qPCR and luciferase reporter assays were carried out. Biochemical and cellular techniques were employed to assess cellular injury and lipid peroxidation levels. The extent of ferroptosis was evaluated through transmission electron microscopy (TEM). Results KLF6 levels were significantly increased in a renal IRI model. Knockdown of KLF6 using AAV9 reduced kidney injury in both in vitro and in vivo models, while KLF6 overexpression aggravated injury. Overexpression of KLF6 promoted ferroptosis, whereas its knockdown reduced lipid peroxidation and ferroptosis. KLF6 regulates NCOA4 expression by binding to its promoter, controlling ferroptosis. Knockdown of NCOA4 in vitro alleviated ferroptosis and cellular damage caused by KLF6 overexpression. Pharmacological inhibition of KLF6 reduced kidney injury and ferroptosis in S-AKI mice. Conclusion Our study uncovered a previously unrecognized role for KLF6 in S-AKI. By facilitating NCOA4 transcription, KLF6 intensified ferroptosis, which, in turn, aggravated septic AKI.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 17
·9159
·
IF 13.3
Tianyi Wu,Yun Teng,Dawei Song,Yuqi Yang,Huaishuang Shen,Xiao Sun,Rui Chen,Leyu Zhao,Xianggu Zhong,Qi Yan,Junjie Niu,Jun Ge,Liang Cheng,Jun Zou
Background: Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, yet current therapies fail to reverse the degenerative process or restore disc function. Ferroptosis, a form of iron-dependent cell death characterized by lipid peroxidation, has been implicated in IVDD progression. Methods: We synthesized Deferoxamine mesylate (DFOM)-loaded cerium oxide nanoparticles (DFOM@CeO 2 ) as a novel ferroptosis-targeting therapeutic. Results: DFOM@CeO 2 exhibited dual functionality by scavenging reactive oxygen species (ROS) and chelating excess iron, thereby protecting nucleus pulposus (NP) cells from ferroptosis and extracellular matrix (ECM) degradation. DFOM@CeO 2 demonstrated strong antioxidant capacity, effectively reducing iron accumulation and lipid peroxidation, and restoring glutathione peroxidase 4 (GPX4) expression in NP cells. Furthermore, DFOM@CeO 2 improved mitochondrial respiratory chain function, reduce mitochondrial ROS production and prevent mitochondrial dysfunction. In a rat model of IVDD, DFOM@CeO 2 significantly preserved disc height, reduced ECM degradation, and demonstrated superior therapeutic efficacy compared with DFOM or CeO 2 alone. Transcriptome analysis revealed that DFOM@CeO 2 modulates key ferroptosis-related genes and promotes mitochondrial reprogramming. Conclusions: These findings highlight DFOM@CeO 2 as a promising therapeutic strategy for IVDD, targeting both ferroptosis and mitochondrial dysfunction.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Jing Li,Hongbo Wu,Hanyue Li,Yue Zhang,Hanjie Zhang,Ling Wang,Weilang Zhang,Tingxuan Li,Weiwei Zeng,Daquan Chen,Lin Mei
The clinical translation of catalytic therapy has been hindered in recent decades due to immunological risks, delayed degradation, and poorly understood metabolism associated with catalysts, despite promising results in antitumor therapy. Developing catalysts with nonmetallic active centers may provide an alternative to those with metallic active centers. In this study, a natural protein nanocatalyst, Hb@PtPP, is developed through the moderate polymerization of pyrrole and hemoglobin for tumor catalytic therapy. In comparison with BSA@PtPP prepared from bovine serum albumin, Hb@PtPP exhibits distinctive autoxidation activity in tumor cells in response to elevated hydrogen peroxide levels while maintaining relatively low activity in normal cells. This feature enables Hb@PtPP to effectively combat tumors by initiating a cascade of catalytic reactions, including the production of reactive oxygen species, the release of heme and iron ions, and the accumulation of lipid peroxidation, all of which contribute to apoptosis and ferroptosis in tumor cells. RNA-sequencing results further demonstrate that tumor cells undergo ferroptosis. Additionally, these catalytic processes are augmented by the photothermal effect, resulting in efficient tumor killing and growth inhibition both in vitro and in vivo . This study underscores the crucial role of hemoglobin in advancing catalytic therapy for tumors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2025
·
IF 4.1
Haipeng He,Lei Chen,Jiaxin Peng,Jinyan Guo,Xue Xiao,Chaoxun Dou,Huining Chen,Songbiao Zhan,Xue Han,Weifeng Yao
Oxidative stress, particularly ROS accumulation, plays a key role in the development of abdominal aortic aneurysm (AAA). Surgical treatments and current drugs for AAA have limitations, including lack of specificity and significant side effects. This study constructed ROS-responsive nanoparticles using phenylthio-modified dendritic polylysine (PDP) loaded with selenomethionine (PDPs-Se) for AAA treatment, and elucidated its mechanism of action. In-vitro studies revealed that PDPs-Se enhanced the clearance of ROS by increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) while reducing malondialdehyde (MDA) levels. Furthermore, PDPs-Se upregulated the expression levels of GPX4, SLC7A11, and FTH1 to suppress ferroptosis and modulate the differentiation of vascular smooth muscle cells (VSMCs) from a synthetic to a contractile phenotype. In-vivo experiments revealed that PDPs-Se attenuated the progression of AAA by inhibiting oxidative stress responses and improving the aortic wall thickness, indicating its potential as an approach for AAA therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2024
·Vol. 17
·期 1
·1-16
·
IF 3.8
Wang Shiwei,Wu Xuan,Yang Juan,Peng Yuwan,Miao Fulu,Li Min,Zeng Juan
Background Sterigmatocystin (STE) is a mycotoxin widely found in contaminated food and foodstuffs, and excessive long-term exposure to STE is associated with several health issues, including infertility. However, there is little information available regarding the effects of STE toxin on the female reproductive system, particularly concerning oocyte maturation.Methods In the present study, we investigated the toxic effects of STE on mouse oocyte maturation. We also used Western blot, immunofluorescence, and image quantification analyses to assess the impact of STE exposure on the oocyte maturation progression, mitochondrial distribution, oxidative stress, DNA damages, oocyte ferroptosis and asymmetric division defects.Results Our results revealed that STE exposure disrupted mouse oocyte maturation progression. When we examined the cellular changes following 100 µM STE treatment, we found that STE adversely affected polar body extrusion and induced asymmetric division defects in oocytes. RNA-sequencing data showed that STE exposure affects the expression of several pathway-correlated genes during oocyte meiosis in mice, suggesting its toxicity to oocytes. Based on the RNA-seq data, we showed that STE exposure induced oxidative stress and caused DNA damage in oocytes. Besides, ferroptosis and α-tubulin acetylation were also found in STE-exposed oocytes. Moreover, we determined that STE exposure resulted in reduced RAF1 protein expression in mouse oocytes, and inhibition of RAF1 activity also causes defects in asymmetric division of mouse oocytes.Conclusion sCollectively, our research provides novel insights into the molecular mechanisms whereby STE contributes to abnormal meiosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Chao Zhao,Xiaoyan Huang,Zhuoyang Wu,Wanlu Sun,Yi Pan,Yi Liu
The activatable upconversion photosensitizer is a type of photosensitizer that can be activated in the tumor microenvironment (TEM) to achieve precise photodynamic therapy. As an inducer of ferroptosis, it is difficult for RSL3 to target tumor cells accurately and may be toxic to normal tissues. Thus, we developed a pH-responsive self-assembled near-infrared upconversion photosensitizer (Re-NPs) and encapsulated RSL3 drugs (RSL3@Re-NPs) to induce ferroptosis synergistically. The RSL3@Re-NPs can effectively release RSL3 under acidic conditions in TEM, and they can generate singlet oxygen under 808 nm. Through the combination of RSL3 and a photosensitizer, the specific release of the drug and the accumulation of lipid peroxide were realized. In vitro and in vivo results showed that RSL3@Re-NPs had good biocompatibility and significantly inhibited tumor cell proliferation by inducing cell ferroptosis. This combination strategy provides new ideas and methods for tumor treatment, which is expected to improve the efficacy of tumor treatment and reduce side effects.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Hui Zhi,Weimin Yin,Shiyu Chen,Xiaoyou Zhang,Zichen Yang,Fulong Man,Rongjie Li,Yanni Cai,Yang Li,Caoyi You,Yan Li,Yongyong Li,Haiqing Dong
Cuproptosis and ferroptosis exhibit superior synergistic advantages in antitumor therapy. While glutathione (GSH) has been identified as a key molecule in enhancing the synergistic effects of these two processes, inherent cellular redox homeostasis mechanisms limit its therapeutic efficacy. This inspired us to explore other new regulators to potentiate the synergistic effect. Through bioinformatics analysis and preliminary experimental validation, we discovered that lactate metabolism is closely associated with both ferroptosis and cuproptosis. Therefore, this work strategically targets lactate metabolism to synergistically activate cuproptosis and ferroptosis, and elucidate its immunotherapeutic mechanisms. For this purpose, we constructed a Syr-loaded nanodelivery system (Syr@mPDA@CP) using biocompatible mesoporous polydopamine (mPDA) as the carrier. Upon targeted to tumor tissues, the released Syr significantly inhibits lactate efflux, leading to intracellular lactate accumulation. This lactate buildup further induces intracellular acidification, exerting dual effects: (1) promoting ferritin (FTH1) dissociation to release endogenous iron stores, thereby elevating intracellular iron levels; and (2) suppressing glycolysis and reducing ATP levels, which inactivates the copper export protein ATP7B. Combined with copper peroxide (CP)-derived Cu 2+ , these effects synergistically amplify intracellular copper accumulation. The elevated intracellular Cu and Fe concentrations subsequently induce dual cell death pathways of cuproptosis and ferroptosis, effectively enhancing cancer immunotherapy. This study pioneers a lactate metabolism-regulating strategy to synergistically amplify both ferroptosis and cuproptosis, offering novel perspectives for antitumor therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-19
·
IF 12.6
Du Chunhong,Wang Shuai,Cheng Yijie,Li Jie,Zhang Yufei,Li Zhuohao,Zhu Baolin,Wu Zhongming,Zhang Xinge,Zhou Lingyi
Pneumonia caused by Pseudomonas aeruginosa ( P. aeruginosa ) infection remains a formidable clinical challenge due to persistent biofilm formation and intrinsic antibiotic resistance, exacerbated by bacterial iron homeostasis that stabilizes biofilm architecture and neutralizes oxidative stress. Herein, we present Fe/TNT@NM, a biomimetic nanosonosensitizer activated by ultrasound (US) to dismantle biofilms through dual extracellular-intracellular mechanisms. The nanosonosensitizer features an iron-doped titanate nanotube (Fe/TNT) core encapsulated within a neutrophil membrane (NM). Under US irradiation, Fe/TNT@NM generates sonodynamic reactive oxygen species (ROS) extracellularly and enhances Fe 3+ release. These ions catalyze the Fenton reaction extracellularly to amplify chemodynamic effects and disrupt intracellular iron homeostasis, triggering bacterial ferroptosis. The NM coating enables immune evasion and biofilm-targeted delivery. This ultrasound-reinforced ferroptosis strategy synchronizes extracellular ROS storms with intracellular iron dyshomeostasis, achieving dual-action biofilm dismantling and eradication of drug-resistant P. aeruginosa . In a murine pneumonia model, Fe/TNT@NM suppresses biofilms and mitigates pulmonary injury. By converging biomimetic targeting, sonodynamic-chemodynamic cascades, and ultrasound-augmented ferroptosis, this nanosonosensitizer presents a paradigm-shifting approach to combat refractory biofilm infections and antibiotic resistance. Graphical
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xinghua Yu,Yujun Zhang,Lingan Zeng,Haiyan Chen,Xuemei Dong,Tianfu Zhang,Ben Zhong Tang,Fei Sun
Asthenozoospermia, a major cause of male infertility characterized by impaired sperm motility, is critically driven by oxidative stress and dysregulated iron metabolism, which directly induce ferroptosis in sperm cells. To address this, a novel nanotheranostic platform utilizing ferritin nanocages to encapsulate vitexin, a natural flavonoid with potent antioxidant properties and unique aggregation-induced emission (AIE) characteristics, is introduced. This ferritin nanocage-loaded vitexin (HFn@VI) system combines the iron-chelating capability of ferritin with vitexin's ability to mitigate oxidative stress, enabling precise dual-targeting of the ferroptotic pathways in spermatogenic cells. In the asthenozoospermia model mice, HFn@VI significantly improves sperm count and kinematic parameters (motility, velocity) without observable systemic toxicity, demonstrating superior therapeutic efficacy. Mechanistic studies reveal that the ferritin component elevates ferritin heavy chain 1(FTH1) levels, sequestering free iron ions and reducing cellular iron overload. Concurrently, vitexin activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, enhancing glutathione peroxidase 4 (GPX4) expression to inhibit lipid peroxidation and ferroptosis. This study pioneers the application of vitexin, a natural product exhibiting AIE characteristics, as a therapeutic agent in reproductive medicine and underscores the potential of dual-target nanomedicines for precise ferroptosis intervention, establishing a new paradigm for treating male infertility through advances in material science.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）