JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Lin Zhang,Wen-Yao Shi,Jia-Ying Xu,Yan Liu,Shi-Jia Wang,Jia-Yang Zheng,Yun-Hong Li,Lin-Xi Yuan,Li-Qiang Qin
Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys 2 ) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant ( Cardamine hupingshanensis )-derived SeCys 2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys 2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys 2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys 2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys 2 -enriched agricultural products.
研究领域:
毒理学
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药理学
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细胞生物学
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植物科学
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DOI
PubMed
高影响因子
Nano Today
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2025
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IF 10.9
Danfeng Jian,Kai Ye,Limo Wang,Lulu Jin,Huang Yang,Lie Ma,Chenggang Yi,Zhengwei Mao,Jindan Wu
Improving efferocytosis of dendritic cells (DCs) by inhibiting membrane transporter protein SLC7A11 has been explored for healing diabetes wounds. However, the administration of SLC7A11 inhibitors has been linked to the generation of reactive oxygen species (ROS), which may compromise the viability and functionality of DCs. To mitigate this adverse effect, a nanozyme-loaded nanofiber dressing, termed GIPH, was developed. This dressing encapsulates a specific SLC7A11 inhibitor (HG106) in the core layer and incorporates an efficient nanozyme, Ir NPs-PVP, in the shell layer. The Ir NPs-PVP nanozyme effectively neutralizes ROS produced by HG106, thereby enhancing the viability of DCs and further promoting their efferocytosis. Our in vitro experiment results demonstrated that GIPH-treated Bone Marrow-Derived Dendritic Cells (BMDCs) exhibited a 1.68-fold increase in survival and a 1.52-fold enhancement in efferocytosis rate compared to those treated with HG106 alone. Furthermore, in a diabetic mouse wound model, the GIPH group showed superior healing outcomes, with wound nearly achieving complete recovery by day 12 (97.5 %). This research highlights the therapeutic potential of nanozyme-loaded nanofiber dressings while providing valuable insights for future investigations into the DCs-mediated wound healing process.
研究领域:
生物医学工程
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免疫学
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糖尿病研究
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DOI
高影响因子
Journal of Radiation Research and Applied Sciences
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2025
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IF 2.5
Yu Zhang,Hongbo Lv,Chao Chen,Zixu Li,Zhaoyu Xie,Miaomiao Wu,Zhixu Zhu,Ying Fan,Jing Li,Qiang Gao,Jun Han,Hui Che,Lan Ma
Background Ischemic stroke (IS) is a major global cause of mortality and long-term disability, and effective therapies are urgently needed. Hydrogen sulfide (H 2 S) has shown neuroprotective effects in various neurological disorders, but its mechanisms in IS remain unclear. This study aims to explore the role and mechanism of H 2 S in IS treatment. Methods IS models were established in vivo using middle-cerebral-artery occlusion (MCAO) in rats and in vitro using oxygen-glucose deprivation/reoxygenation (OGD/R) in PC12 cells. These models were treated with H 2 S donors NaHS or GYY4137. Pathological features were evaluated using TTC, FJC, H&E, and Nissl staining. Cell viability was assessed with live/dead staining and CCK-8 assay. RNA sequencing identified gene expression changes after H 2 S treatment under OGD/R conditions. Ferroptosis-related markers, lipid peroxidation (GSH, SOD, MDA), ROS levels, and the expression of SLC7A11 and GPX4 were measured by flow cytometry, Western blot, and immunofluorescence. MiR-27a levels were quantified by qRT-PCR. Results NaHS administration in MCAO rats reduced infarct volume, increased Nissl body density, and decreased degenerating neurons. GYY4137 exhibited similar neuroprotective effects in vitro. RNA sequencing revealed that GYY4137 reversed ferroptosis-related gene changes, including SLC7A11. H 2 S supplementation inhibited neuronal ferroptosis, shown by increased SLC7A11 and GPX4 expression, elevated GSH and SOD levels, and reduced MDA content. Additionally, MCAO or OGD/R induced miR-27a expression, which negatively regulated SLC7A11. H 2 S reversed this induction, and miR-27a overexpression partially blocked the anti-ferroptotic effect of H 2 S. Conclusion H 2 S alleviated IS-induced brain injury by suppressing ferroptosis, partially through miR-27a-dependent regulation of SLC7A11. These findings suggest H 2 S as a promising therapeutic agent for IS, warranting further clinical exploration.
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高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Mingyue Yan,Kehao Hou,Jinpeng Zhao,Shuangshan Li,Xiaolin Wu,Shichao Bi,Jing Yu,Tianrui Wang,Yingze Zhang
The characteristic pathological manifestations of rheumatoid arthritis (RA) include inflammatory cell infiltration, abnormal synoviocyte proliferation, and progressive bone and cartilage destruction. An excessive buildup of reactive oxygen species (ROS) within the joints is a critical factor promoting RA pathological progression. In this study, we innovatively employed a hard template-restricted controlled sintering carbonization strategy to fabricate ultra-small Fe 3 O 4 @C nanoparticles with hierarchical structures. The ultra-small Fe 3 O 4 @C nanoparticles exhibit multiple natural enzyme-mimic catalytic activity, effectively diminishing intracellular ROS levels in macrophages, while also facilitating the polarization toward the M2 phenotype, and significantly suppresses the production of pro-inflammatory cytokines. Mechanistic investigations reveal that Fe 3 O 4 @C significantly suppresses ferroptosis in synoviocytes and chondrocytes through regulation of the SLC7A11/GPX4 signalling pathway, thereby alleviating synovial tissue erosion and promoting type II collagen synthesis. In the collagen-induced arthritis mouse model, Fe 3 O 4 @C exhibited remarkable anti-inflammatory and chondroprotective effects, providing an innovative nanozyme therapeutic approach for RA treatment.
研究领域:
纳米医学
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风湿病学
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免疫学
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生物医学工程
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氧化还原生物学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
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IF 10.2
Linxue Zhang,Xing He,Hongyu Zhu,Qi Sun,Yu Liu,Lin Huang,Tianlong Wen,Jianfu Li,Zhongwen Lan,Zhong Yu,Zhenglin Yang,Kun Jia,Ke Sun,Ziyan Wang
Hepatocellular carcinoma (HCC) remains global health concern due to complex pathogenic mechanism and lack of effective therapeutic drugs. The magnetic hyperthermia therapy (MHT) appears as the promising and safe strategy during the recent exploration of new technology for cancer treatment. Herein, we reported an injectable and magnetic-hydrogel-construct-based thermal regression agent mPEG- b -PLV-Fe 3 O 4 Hybrids in MHT for the first time. Percutaneous thermotherapy was employed as a minimally invasive strategy for treating hepatic tumors in a rabbit model. Based on the evidence in vitro and in vivo studies, we demonstrated that mPEG- b -PLV-Fe 3 O 4 Hybrids under magnetic field, exhibited powerful antitumor effect by inducing massive ROS accumulation, severe lipid peroxidation and damaged mitochondria, which together triggered triple forms of cell death: ferroptosis, autophagy and apoptosis. Furthermore, we revealed that mPEG- b -PLV-Fe 3 O 4 Hybrids under magnetic field reprogramed the cysteine-glutathione metabolism by suppressing SLC7A11 expression, which aggravated redox imbalance and suppresses cell survival. The hybrids achieve outstanding therapeutic results in mouse and rabbit models. Our findings underscore that mPEG- b -PLV-Fe 3 O 4 Hybrids under magnetic field is a promising strategy for cancer therapy by targeting the SLC7A11-cysteine-glutathione axis.
研究领域:
肿瘤学
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纳米医学
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分子生物学
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转化医学
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生物材料
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肝病学
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细胞死亡机制
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Jingjing Chen,Lu Zhou,Mengxin Li,Jun Wang,Yaru Chen,Jing Xia,Yue Lin,Huizhen Chen,Zibo Dong
Chronic Intermittent Hypoxia (CIH) is a central pathological feature of diseases such as obstructive sleep apnea hypopnea syndrome (OSAHS), which induces oxidative stress in lung tissues and leads to lung injury. Atraric acid (AA), a lichen-derived compound, has been reported to possess anti-inflammatory and antioxidant activities. In this study, we investigated the functions and mechanisms of AA in CIH-induced lung injury by constructing a CIH mouse model and an in vitro hypoxia/reoxygenation model in MLE-12 cells. Various methods were employed, including hematoxylin and eosin (H&E) staining, biochemical assay kits, quantitative polymerase chain reaction (qPCR) analysis, protein blotting, immunofluorescence, and flow cytometry. The results showed that AA pretreatment significantly attenuated pathological injury of mouse lung tissue, reduced pulmonary edema, reactive oxygen species (ROS) and malondialdehyde production, as well as the depletion of total antioxidant capacity, catalase and glutathione, and lowered the expression levels of inflammatory factors. Mechanistic studies showed that AA up-regulated solute transport family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression and down-regulated prostaglandin-endoperoxide synthase 2 (PTGS2) through activation of the Nrf2 signaling pathway, whereas the Nrf2 inhibitor ML385 completely blocked this protective effect. In conclusion, the present study demonstrates that AA targets the Nrf2 axis, attenuated CIH-induced inflammation, alleviates ROS accumulation, and blocks the vicious cycle of oxidative stress, ferroptosis, and inflammation, making it a promising therapeutic strategy for the treatment of CIH-induced lung injury.
研究领域:
药理学
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分子生物学
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呼吸病学
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生物化学
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细胞生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
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IF 6.8
Yan Wang,Yue Zhang,Jinglong Xue,Leqiang Gao,Xiangyang Li,Moxuan Zhao,Dong Zhao,Xianqing Zhou
Decabromodiphenyl ether (BDE-209) is an environmental toxin. Increasing evidence showed that BDE-209 exposure induced liver injury, but the mechanism still remains unknown. The present study explored the effect and mechanism of ferroptosis on hepatotoxicity triggered by BDE-209 in vivo and in vitro . In vivo experiment, ICR mice were exposed to BDE-209 for 50 days, and then recovered for 50 days; HepG2 and L02 cells were treated with BDE-209 or/and ferrostatin-1 (Fer-1) for establishing in vitro model. In vivo , the results showed that BDE-209 accumulated in liver and induced liver damage, increased Fe 2+ and MDA contents, and blocked the activation of SLC7A11/GSH/GPX4 pathway in liver; BDE-209 also activated IKK/IκB/NF-κB pathway and elevated inflammatory cytokines levels in liver after exposure for 50 days. After BDE-209 stopping exposure 50 days, the severity of liver damage, ferroptosis and inflammatory response were still higher than the corresponding control group. In vitro , ferroptosis inhibitor Fer-1 rescued ferroptotic damage and attenuated cell death in BDE-209-treated HepG2 and L02 cells. In addition, Fer-1 reversed the activation of IKK/IκB/NF-κB pathway and the increase of pro-inflammatory cytokines levels in BDE-209-treated HepG2 and L02 cells. Together, the above results suggested that BDE-209 induced tissue damage and inflammatory response by activating ferroptosis through increasing iron-dependent lipid peroxidation and blocking the activation of SLC7A11/GSH/GPX4 pathway in liver, indicating that ferroptosis is a potential mechanism for BDE-209-induced hepatotoxicity.
研究领域:
毒理学
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肝病学
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细胞生物学
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环境科学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Jingyu Weng,Lang Liu,Shuming Li,Yuangui Yang,Rui Zhou,Zhen Zhang,Yanru Liu,Lin Chen,Zeyu Feng,Zhishu Tang,Hongbo Xu
Background Lipid peroxide accumulation plays significant roles in cerebral ischemia-reperfusion injury (CIRI) through various mechanisms, including ferroptosis. Preserving the neuronal metabolic equilibrium and averting cell death during cerebral Ischemia-reperfusion are pivotal for protecting brain function. Yinaoxin granule (YNX) is a widely used Chinese herbal preparations for treating cerebrovascular diseases, but pharmacological mechanism remains ambiguous.. Purpose The aim in this study was to assess the effectiveness of YNX in treating CIRI and to investigate the underlying mechanisms. Methods The active ingredients of YNX were quantified using high-performance liquid chromatography. To explore the effects of YNX on CIRI and ferroptosis, both an in vitro oxygen-glucose deprivation and reperfusion model and a middle cerebral artery occlusion and reperfusion rat model were used. To assess the neuroprotective effects of YNX in the latter, neurological scores and cerebral blood flow were evaluated. Neuronal damage was determined through 2,3,5-triphenyltetrazolium chloride, Nissl, and H&E staining. Ferroptosis-related markers, including ferrous ion, glutathione, 4-hydroxynonenal, and malondialdehyde were also investigated. Furthermore, the gene expression and protein levels of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4) and glutamate-cysteine ligase modulator (GCLM) were determined. Results YNX enhanced neurological scores and cerebral blood flow, reduced infarct volume, and rescued necrotic neurons in rats. Additionally, YNX mitigated lipid peroxidation and upregulated the SLC7A11, GCLM, and GPX4 levels. The absence of Nrf2 rendered neurons more susceptible to ischemia-reperfusion damage and abrogated the anti-ferroptotic neuroprotective effects of YNX. Conclusion YNX activates the Nrf2 pathway, resulting in the transcription of genes associated with antioxidants, including SLC7A11, GCLM, and GPX4. This suggests that YNX reduces lipid peroxidation and alleviates ferroptosis-induced CIRI.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Cell Death & Disease
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2022
·Vol. 13
·期 11
·1-12
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IF 9.685
Hu Xiaomeng,He Yuchao,Han Zhiqiang,Liu Wei,Liu Dongming,Zhang Xihao,Chen Lu,Qi Lisha,Chen Liwei,Luo Yi,Li Qiang,Chen Peng,Wu Qiang,Zhu Xiaolin,Guo Hua
Effective strategies for hepatocellular carcinoma, which is the second leading cause of death worldwide, remain limited. A growing body of emerging evidence suggests that ferroptosis activation is a novel promising approach for the treatment of this malignancy. Nevertheless, the potential therapeutic targets and molecular mechanisms of ferroptosis remain elusive. In this study, we found that PNO1 is a bona fide inhibitor of ferroptosis and that autophagy induced by PNO1 promotes cystine/glutamate antiporter SLC7A11 while increasing the synthesis and accumulation of intracellular glutamate. This increase is followed by an equally proportional addition in cystine uptake, which consequently enhances system Xc - activity that leads to the inhibition of ferroptosis. In the maintenance of redox homeostasis, system Xc - activated via PNO1-autophagy metabolism is responsible for maintaining cysteine for glutathione (GSH) synthesis, and the final GSH metabolic reprogramming protects HCC cells from ferroptosis. The combination of PNO1 inhibition with drugs causing ferroptosis induction, particularly sorafenib, the first-line drug associated with ferroptosis in liver cancer shows therapeutic promise in vitro and in vivo. Together, our findings indicated that PNO1 protects HCC cells from ferroptotic death through autophagy-mediated GSH metabolic remodeling, and we identified a candidate therapeutic target that may potentiate the effect of ferroptosis-based antitumor therapy.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2026
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IF 7.8
Zijia Jiang,Yifan Zhao,Zequn Li,Huimei Jiang,Bai Lv,Jie Cao
Photodynamic therapy (PDT) faces significant challenges in clinical applications, including tumor hypoxia, the poor water solubility of photosensitizers, and insufficient targeting specificity. To address these limitations, we developed a biomimetic nanoagonist, 4T1@MFCB, by coloading a near-infrared photosensitizer (CyI) and a GLUT1 inhibitor (BAY-876) into a manganese/iron bimetallic metal–organic framework (MOF), followed by coating with the homologous 4T1 cell membrane. The manganese component catalyzes the decomposition of endogenous H2O2 to generate oxygen, alleviating tumor hypoxia and enhancing PDT efficacy, while the iron component promotes ferroptosis via the Fenton reaction. Meanwhile, BAY-876 inhibits glucose uptake, disrupting NADPH production and the cystine-to-cysteine reduction process, which leads to cystine accumulation and glutathione (GSH) depletion. These effects collectively suppress the Solute Carrier Family 7 Member 11(SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) antioxidant axis, thereby triggering disulfidptosis. Under near-infrared irradiation, CyI mediates effective photodynamic and photothermal therapy (PTT). Both in vitro and in vivo studies demonstrate that 4T1@MFCB enables synergistic PDT/ferroptosis/disulfidptosis therapy, significantly inhibiting tumor growth without obvious systemic toxicity. This work highlights a multimodal treatment strategy that integrates metabolic intervention with nanocatalytic therapy, providing a promising approach for the precision treatment of hypoxic and therapy-resistant tumors.
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PubMed
高影响因子
DRUG RESISTANCE UPDATES
·
2026
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IF 21.7
Lianli Ni,Hailong Li,Peipei Chen,Yun Yu,Chenjun Xie,Wenfeng Hong,Gaowei Fang,Baohong Wan,Yiwei Shen,Peng Zou,Wangyu Zhu,Zhiguo Liu,Xiaokun Li,Ri Cui
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and the leading cause of cancer-related deaths globally. The RNA binding protein Quaking-5 (QKI-5) has been established as a tumor suppressor in NSCLC. Inducing ferroptosis is regarded as an effective therapeutic strategy for cancer treatment, and long non-coding RNA (lncRNA) plays a critical role in the regulation of ferroptosis. However, the relationship between QKI-5-regulated lncRNA and ferroptosis remains uncharacterized in NSCLC. In this study, we discovered that QKI-5 downregulates the oncogenic lncRNA linc01833, which inhibits ferroptosis and promotes NSCLC progression by activating SLC7A11/GPX4 signaling pathway. Mechanistically, QKI-5 negatively regulates the stability of linc01833, leading to increased linc01833 expression in NSCLC. Silencing linc01833 enhanced WW domain-containing E3 ubiquitin protein ligase 1 (WWP1)-mediated ubiquitination of SLC7A11, resulting in decreased SLC7A11 expression, while overexpression of linc01833 produced the opposite effect. Further analyses demonstrated that linc01833 diminished the anti-tumor effect of gemcitabine (GEM) in NSCLC both in vivo and in vitro . Additionally, knocking down linc01833 or SLC7A11 is able to inhibit GEM resistant NSCLC growth. Our findings suggest that targeting linc01833 to induce ferroptosis could enhance the cytotoxic effects of chemotherapeutic agents and may serve as an effective therapeutic strategy for some NSCLC patients.
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PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Ziting Zhang,You Ji,Nan Hu,Qinqi Yu,Xinrui Zhang,Jie Li,Fenglei Wu,Huae Xu,Qiyun Tang,Xiaolin Li
Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation, which may be a potential strategy for cancer therapy. Here we demonstrated for the first time that Resveratrol (RSV), a traditional Chinese medicine (TCM) chemical monomer, could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway. Mechanistically, RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells, and eventually lead to ferroptosis. Furthermore, RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). To improve the delivery efficiency of RSV, a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)–poly(ethylene glycol) (PCL-PEG) nanoparticles with erythrocyte membrane ( [email protected] ). The [email protected] provide the possibility to escape macrophage phagocytosis and have a long circulation effect. In addition, when coupled with a tumor-penetrating peptide iRGD, which could trigger enhanced tissue penetration tumor-specifically, the delivery of [email protected] into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC. Altogether, our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform, it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.
研究领域:
肿瘤学
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药理学
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
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