Advanced Healthcare Materials
·
2026
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IF 11
Yanlin Li,Xiaotian Jiang,Jiale Li,Hanwen Gu,Qi Li,Jiaxin Li,Yunqing Ji,Xiang Min,Bin Chen,Qingjia Xu,Junhao Lin
Osteoarthritis (OA), a prevalent degenerative joint disorder characterized by articular cartilage deterioration, represents a major global health challenge. Recent studies highlight the pivotal role of reactive oxygen species (ROS)-mediated ferroptosis in OA pathogenesis. Here, we report a microenvironment-adaptive hydrogel system based on 2D vanadium nitride (V 2 N) MXene nanoenzyme (hereafter denoted as V 2 N MXenzyme@Gel). This system features a dual-crosslinked network that optimally balances between mechanical robustness and flexibility. Crucially, the V 2 N MXenzyme establishes a self-sustaining “capture-conversion-recycling” catalytic cycle, mimicking both superoxide dismutase (SOD) and catalase (CAT) activities. The cycle not only neutralizes detrimental ROS into water (H 2 O) and oxygen (O 2 ) but also generates nitric oxide (NO), collectively alleviating oxidative damage. Mechanistically, V 2 N MXenzyme@Gel effectively scavenges ROS, attenuates oxidative stress, and suppresses ferroptosis by regulating the Hspa5/GPX4 axis, while concurrently restoring the metabolic homeostasis of chondrocyte extracellular matrix (ECM). Meanwhile, intra-articular administration of V 2 N MXenzyme@Gel significantly attenuates cartilage degradation and inflammation levels in OA rats. Collectively, our work presents a V 2 N MXenzyme@Gel with dual capabilities for ROS elimination and ferroptosis blockade, demonstrating its efficacy in arresting OA progression and proposing a novel precision strategy for managing chronic joint diseases.
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高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Yingxia Hu,Haijie Wu,Chenying Lu,Hanqing Xu,Boyang Li,Wanchun Guan,Mingjiang Wu,Yitian Gao,Haibin Tong
Cadmium (Cd) is a widely distributed toxic heavy metal that enters the environment via anthropogenic mobilization and accumulates in plants and animals, causing metabolic abnormalities even mortality. Although the toxic effects and stress damage of cadmium have been investigated extensively over the past few decades, research on its ability to trigger ferroptosis, growth retardation, and behavioral abnormalities is insufficient. As a result, the effects of CdCl 2 exposure on growth and development, activity and sleep, and ferroptosis in this study were examined in fruit fly ( Drosophila melanogaster ). When exposed to 0.5 mM CdCl 2 , the entire growth period from larvae to adults was prolonged, and the rates of pupation and eclosion were decreased. Additionally, CdCl 2 exposure resulted in a decrease in body weight and individual size of fruit fly and high lethality rate. Moreover, CdCl 2 exposure altered fruit fly behavior, including decreased activity and increased sleep duration, particularly in females. Ferrostatin-1 (Fer-1) is a potent selective ferroptosis inhibitor that effectively slows lipid hydroperoxide accumulation to rescue body size reduction and restore activity and sleep in CdCl 2 -exposed female flies. CdCl 2 exposure could induce ferroptosis in fruit fly mechanistically, as evidenced by inhibition of Nrf2 signaling pathway, accumulation of lipid peroxidation, impairment of GPX4 antioxidant system, and upregulation of iron metabolism. Our findings suggest that Cd exposure triggers ferroptosis, which leads to growth retardation and behavioral disorders in fruit fly.
研究领域:
毒理学
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发育生物学
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神经科学
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·735
·
IF 12.6
Song Dake,Li Jianing,Zhu Yidan,Hui Qijun,Qi Hengkai,Yu Hanrui,Chen Lin,Qian Yue,Guo Yuanyuan,Wei Minjie,Guan Qiutong,Li Zhenhua
Despite the promise of ferroptosis in cancer therapy, its insufficient potency and off-target toxicity remain significant challenges. Few studies have explored the therapeutic potential of nanoparticle (NP)-mediated active targeting strategies to induce robust ferroptosis in colon cancer (COC) cells effectively. In this study, we developed sialic acid (SA)-targeted NPs by conjugating artesunate (ART) with alanine (Ala) and phenylboronic acid (PBA) to formulate ART-Ala-PBA NPs (AAP NPs). Compared with nontargeted ART-Ala NPs, AAP NPs accumulated significantly within cancer tissues, inhibited tumor growth, and improved the survival rates of mice with COC, while exhibiting minimal toxicity. Mechanistically, AAP NPs induce ferroptosis through the accumulation of reactive oxygen species and the downregulation of the SLC7A11-GPX4 axis. Deep data-independent acquisition (DIA) proteomics revealed a novel suppression of ribonucleotide reductase regulatory subunit M1 (RRM1), which synergizes with canonical ferroptosis pathways to amplify lipid peroxidation. RNA sequencing further indicated that AAP NPs uniquely modulate autophagy-related processes, suggesting a multimodal mechanism distinct from the alterations in amino acid metabolism induced by parental ART formulations. Collectively, AAP NPs represent the first carrier-free nanoassembly leveraging PBA-mediated SA targeting to co-activate ferroptosis via dual ROS/GPX4-RRM1 regulation, offering a translatable paradigm for precision nanotherapy of COC. Graphical abstract
研究领域:
纳米医学
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癌症治疗
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分子靶向治疗
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氧化还原生物学
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药剂纳米技术
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DOI
PubMed
高影响因子
Redox Biology
·
2025
·
IF 11.9
Lu Li,Yu Cao,Xiangsheng Zhang,Jiayi Guo,Ziqiang Lin,Pengyu Zhou,Chuyin Chen,Jiahao Chen,Yike Liu,Danzhi Luo,Jiurong Chen,Yingdong Deng,Peng Sun,Zhiwen Zeng,Jun Zhou
Spinal cord injury (SCI) induced neuropathic pain (NP) remains a major clinical challenge due to persistent neuroinflammation and oxidative stress. We developed an injectable methacrylated and thiolated gelatin hydrogel loaded with quercetin (MSQ) to synergistically scavenge reactive oxygen species (ROS) and inhibit microglial ferroptosis for NP alleviation and neural repair. The MSQ hydrogel exhibited rapid photocrosslinking, sustained quercetin release, and robust ROS scavenging via thiol groups and quercetin, maintaining intracellular redox homeostasis. MSQ attenuated LPS-induced ferroptosis in BV2 microglia by upregulating Nrf2 expression, promoting its nuclear translocation, and activating the Slc7a11/Gpx4 pathway, thereby reducing lipid peroxidation and inflammatory cytokine release. Network pharmacology and molecular dynamics simulations confirmed quercetin's high-affinity binding to Nrf2. In a murine SCI model, MSQ implantation significantly reduced lesion area, suppressed microglial ferroptosis, and decreased pro-inflammatory mediators (TNFα, IL-1β, IL-6), while enhancing neuronal survival (Nissl/NeuN + cells) and axonal regeneration (MAP2/5-HT + expression). Motor functional recovery assays revealed improved BMS scores, gait regularity, and mechanical/thermal pain thresholds in MSQ-treated mice. This study highlights MSQ hydrogel as a multifunctional therapeutic platform that targets ROS homeostasis and microglial ferroptosis via the Nrf2/Slc7a11/Gpx4 axis, offering a promising strategy for post-SCI NP management and neural regeneration.
研究领域:
生物材料
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神经科学
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药理学
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再生医学
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生物化学
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炎症研究
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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
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肾病学
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细胞生物学
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分子生物学
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PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6.8
Lie-Feng Ma,Li−Li Xu,Ling-Jie Yuan,Xi Yang,Rui Wu,Shu-Min Bao,Yi-Li Chen,Hong-Liang Duan,Luo Fang,Hua-Jun Zhao,Zha-Jun Zhan
Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure−activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
Discover Oncology
·
2024
·Vol. 15
·期 1
·1-11
·
IF 2.8
Jiang Xinru,Li Hongdan,Liu Yang
Objective Hepatocellular carcinoma (HCC) is one cancer with high death rates. Nowadays, there are no effective drugs to treat it. Cyclovirobuxine D (CVB-D) is the primary ingredient of the traditional Chinese medicine (TCM) Buxus microphylla . Here, we try to explore the impacts of CVB-D on human HCC cells and explain the potential mechanisms. Methods HepG2 and Huh-7 cells were used for our experiments. The cell viability and half inhibitory concentration (IC50) were detected by MTT assays. The apoptosis ratio was examined by Annexin V-FITC/7AAD staining and flow cytometry (FCM). The Fe 2+ content was examined by ferrous ion content assays. The malondialdehyde (MDA) content was evaluated by lipid peroxidation MDA assays. The reactive oxygen species (ROS) level was examined by the DCFH-DA probe. The expression of apoptotic markers (Bax and Bcl-2) and ferroptosis-related proteins (GPX4 and FSP1) was detected by western blotting. The in vivo curative effect of CVB was explored using xenograft models established in C-NKG mice. Results The cell viability could be inhibited by CVB-D in HepG2 and Huh-7 cells. The IC50 value of CVB-D on HepG2 and Huh-7 cells are 91.19 and 96.29 µM at 48 h, and 65.60 and 72.80 µM at 72 h. FCM showed that the apoptosis rate was increased by CVB-D in HepG2 and Huh-7 cells. Next, ferrous ion content assays showed that the level of Fe 2+ was increased by CVB-D in HepG2 and Huh-7 cells. Then, we found the level of MDA and ROS was increased by CVB-D. And the Fe 2+ promotion by CVB-D could be reversed by Fer-1. Additionally, western blotting assays showed that the expression of GPX4 and FSP1 was inhibited by CVB-D in HepG2 and Huh-7 cells. Moreover, in vivo, CVB-D displayed excellent anticancer effects in HCC tumor-bearing C-NKG mice. Conclusion CVB-D suppresses the growth in HCC cells through ferroptosis.
研究领域:
肿瘤学
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药理学
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细胞生物学
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中医药
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高影响因子
EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Sihan Shen,Ran Xie,Yiqun Wang,Lingyu Jia,Zhangran Zhu,Hai Ma,Lifang Wang,Feng Sui,Yu Zhao,Qinghe Zhao,Yanjun Chen
Ferroptosis represents a novel procedure of programmed cell death driven by iron-dependent lipid peroxidation, and may offer a promising strategy for cancer therapy. In this study, we developed poly (2-ethyl-2-oxazoline)-poly (lactic acid)-SS-poly (β-amino ester) (PEOz-PLA-SS-PBAE) loaded with β-elemene. The disulfide bond mediated depletion of glutathione (GSH) and inactivation of glutathione peroxidase 4 (GPX4) will lead to inactivation of the antioxidant system of the tumor cell, and β-elemene has the capacity to generate reactive oxygen species (ROS), and the above changes would induce a disruption of the redox balance within the tumor cell, resulting in ferroptosis of the tumor cell. In conclusion, in this study, water insoluble β-elemene was solubilized by the triblock copolymer to construct a pH/GSH dual-responsive nano-delivery system, and combined with iron death and chemotherapy to exert combinatory inhibition effect on breast cancer cells, which provides a new idea for the potential clinical application of β-elemene
研究领域:
肿瘤学
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药学
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纳米技术
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DOI
高影响因子
Scientific Reports
·
2024
·
IF 3.8
Si-Chun Gu,Zhi-Guo Xie,Min-Jue Gu,Chang-De Wang,Li-Min Xu,Chen Gao,Xiao-Lei Yuan,You Wu,Yu-Qing Hu,Yang Cao,Qing Ye
Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson’s disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP + ), respectively. Ferroptosis was identified by assessing the levels of Fe 2+ , ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe 2+ , ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP + -induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP + -treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.
研究领域:
神经科学
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药理学
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细胞生物学
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神经退行性疾病
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Ting Zhou,Bao Yang
Prenylated resveratrols are drug candidates presented in many natural sources. They possess multiple pharmacological activities. Due to the limited abundance in nature and disadvantage of chemical synthesis, it is required to produce prenylated resveratrols by biological strategy. In this work, a prenyltransferase iacE from Pestalotiopsis fici was prepared by heterologous overexpression. It could catalyze 2- C -prenylation of resveratrol efficiently. Dimethylallyl diphosphate (DMAPP) and geranyl diphosphate (GPP) could serve as prenyl donor. Glu97, Thr114 and Tyr413 were proved to be important residues in the active site by site-directed mutagenesis. The product was purified and identified to be 2- C -prenyl resveratrol by NMR . 2- C -prenyl resveratrol exerted neuroprotective activity through inhibiting ROS overproduction and improving the activities of antioxidant enzymes in HT22 cell. The genes involved in antioxidant defense were regulated, including upregulated CAT , SOD2 , NFE2L2 , GPx4 , and downregulated PTGS2 and ACSL4 . These results supplied a novel technique for prenylated resveratrols production.
研究领域:
生物技术
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药理学
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神经科学
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PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 4
·1884-1896
·
IF 6.1
Huiyi Li,Qiqing Weng,Shuai Gong,Weixian Zhang,Jiaqi Wang,Yuqiao Huang,Yuanjun Li,Jiao Guo,Tian Lan
Acetaminophen (APAP)-induced liver injury (AILI) has become a growing public health problem. Ferroptosis, an iron-dependent form of cell death associated with lipid peroxide accumulation, has been recently implicated in AILI. The activation of the Nrf2 signaling pathway is a potential therapy for AILI. Kaempferol (KA), a flavonoid widely existing in edible plants, has been reported to exert profound anti-inflammatory and antioxidant activities. This study aimed to investigate whether KA exerts anti-AILI effects via the Nrf2 signaling pathway. Mice were fasted for 22 h and injected intraperitoneally with APAP (250 mg kg−1) to induce AILI. Mice were pre-injected intragastrically with KA for 2 h followed by APAP injection. The hepatic injury was observed by H&E staining. Biochemical parameters of the serum and liver were measured using kits. KA alleviated hepatic injury and inflammatory response in AILI mice and ameliorated APAP-induced hepatic iron overload and oxidative stress in mice. In addition, the protective effects of KA against APAP-induced hepatotoxicity were examined in L02 cells in vitro. Cell viability was assayed by the CCK8 assay. Mitochondrial reactive oxygen species (ROS) in L02 cells were detected by MitoSox fluorescence. KA reversed the APAP-induced decrease in cell viability and GSH levels and inhibited the accumulation of intracellular ROS. Furthermore, KA activated the Nrf2 pathway and upregulated Gpx4 in mouse livers and L02 cells to inhibit ferroptosis induced by APAP. Finally, molecular docking indicated the potential interaction of KA with Keap1. Taken together, KA ameliorated oxidative stress and ferroptosis-mediated AILI by activating Nrf2 signaling.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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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.
研究领域:
肿瘤学
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药理学
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代谢组学
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中医药
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DOI
PubMed
高影响因子
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