FOOD RESEARCH INTERNATIONAL
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2026
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IF 8.8
Yueqin Qiu,Shilong Liu,Xinmiao Liao,Wenjing Wang,Jiaxi Tang,Li Wang,Xuefen Yang,Zongyong Jiang
Geniposide alleviated intestinal barrier dysfunction. • Geniposide increased Prevotella copri abundance to alleviate intestinal injury. • Geniposide inhibited diquat-induced intestinal ferroptosis in vivo and in vitro . • Geniposide regulated TRPV4/GPX4-mediated ferroptosis to alleviated intestinal injury. Early weaning disrupts intestinal antioxidant capacity and barrier integrity in human infants and young animals. Geniposide, an iridoid glycoside, exhibits anti-inflammatory and antioxidant activities. However, the mechanism by which geniposide ameliorates weaning-associated intestinal oxidative injury remains to be elucidated. Therefore, this study aimed to investigate whether and how geniposide attenuates intestinal injury, using diquat (DQ)-challenged weaned piglets, mice, and IPEC-J2 cells as experimental models. The results showed that geniposide supplementation significantly alleviated DQ-induced growth inhibition by increasing ADG and ADFI in the piglets. Additionally, geniposide significantly alleviated DQ-induced intestinal barrier damage, as evidenced by increased gene and protein expression of occludin and claudin-1 and decreased intestinal permeability in the ileum. Moreover, geniposide significantly attenuated DQ-induced oxidative stress, as shown by reduced levels of MDA, ROS, and 4-HNE, along with increased activities of T-AOC, GSH-Px, and T-SOD, as well as upregulated protein abundance of NRF2 and GCLM. Microbiome analysis showed that geniposide significantly increased Prevotella copri abundance in the ileum of DQ-challenged piglets. Prevotella copri supplementation alleviated DQ-induced intestinal injury in mice. Transcriptomic and non-targeted metabolomic analyses revealed that geniposide inhibited the DQ-induced ferroptosis signaling pathway. Additionally, geniposide significantly alleviated the DQ-induced the increases in the levels of MDA and Fe 2+ , and restored expression of the anti-ferroptotic proteins GPX4, SLC7A11, and FTL. Mechanistically, geniposide inhibited DQ-induced intestinal ferroptosis through modulation of the TRPV4/GPX4 pathway and increasing Prevotella copri abundance. Collectively, this study revealed that geniposide alleviated DQ-induced intestinal injury by modulating the TRPV4/GPX4-mediated ferroptosis pathway and increasing Prevotella copri abundance, suggesting its potential as a therapeutic agent against weaning-associated intestinal oxidative damage. Download: Download high-res image (117KB) Download: Download full-size image
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DOI
高影响因子
Pharmaceuticals
·
2026
·Vol. 19
·期 9
·1386
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IF 5.7
Yajun Zhou,Bangjian Liu,Hui Wang,Li Cao
Introduction: Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder involving ROS and ferroptosis. MXene, a 2D material, functions as both a drug carrier and ROS scavenger. Butylphthalide (NBP), a neuroprotective agent, suffers from poor aqueous solubility and bioavailability. This study synthesized Ti2C@BSA-NBP, a novel MXene nanocomposite, to enhance NBP delivery and therapeutic efficacy for AD.Materials and Methods: Ti2C@BSA-NBP was synthesized via self-assembly and amidation reaction, and characterized by multiple techniques. In vitro, ROS-scavenging capacity, mitochondrial function, and ferroptosis markers were assessed in H2O2-injured cells. In vivo efficacy was evaluated in an AD mouse model via behavioral, histopathological, and biochemical analyses. Results: The nanocomposite exhibited robust ROS-scavenging activity in vitro, significantly attenuating ROS, restoring mitochondrial function, and reversing ferroptosis markers. In vivo, Ti2C@BSA-NBP ameliorated learning/memory deficits, partially repaired neuronal morphology, and suppressed neuroinflammation. Mechanistically, it downregulated ACSL4 and Aβ overexpression while restoring GPX4 inhibition.Discussion: Ti2C@BSA-NBP exerts synergistic neuroprotection through MXene-mediated ROS clearance and NBP-mediated multi-target regulation, counteracting oxidative stress, ferroptosis, and neuroinflammation.Conclusions: Ti2C@BSA-NBP is a promising multifunctional nanoplatform integrating antioxidant activity, enhanced drug delivery, and ferroptosis modulation for AD therapy.
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Environment & Health
·
2026
·
IF 8.8
Yueyue Mu,Jiawei Wu,Xiaomeng Ding,Yanting Pang,Yuna Cao,Jing Qu,Haopeng Zhang,Qing Liu,Ting Zhang
Indium tin oxide (ITO) particles, widely utilized in electronics and energy technologies, pose significant pulmonary risks due to occupational exposure during manufacturing. While emerging evidence links ITO to severe lung pathologies, critical gaps persist in understanding size-dependent effects and molecular mechanisms. This study systematically investigates the size-dependent effects of nanoscale ITO (N-ITO) and submicron-scale ITO (U-ITO) on pulmonary toxicity, focusing on ferroptosis as a key mechanism. In vivo, repeated oropharyngeal exposure of mice to ITO (3.6 and 36 mg/kg) induced dose-dependent lung inflammation and ferroptosis, marked by lipid peroxidation, Fe2+ accumulation, and dysregulation of Gpx4 and Scl7a11 proteins, with pulmonary macrophages identified as primary targets. In vitro, THP-1 macrophages exposed to 6.25–25 μg/mL ITO exhibited size-dependent cytotoxicity, inflammation, and ferroptotic hallmarks. Mechanistically, ITO-triggered ferroptosis promoted HMGB1 secretion and nuclear translocation, which activated the RAGE/p38MAPK pathway, amplifying inflammatory responses. Notably, N-ITO induced stronger ferroptosis and inflammation than U-ITO, correlating with enhanced macrophage uptake due to its nanoscale dimensions. Integrating these findings, we propose an Adverse Outcome Pathway (AOP) framework for ITO-induced lung injury, which cellular uptake may serve as the molecular initiating event and link ferroptosis-driven high mobility group protein B1 (HMGB1) release, RAGE/p38MAPK activation, and chronic inflammation to adverse pulmonary outcomes. This study underscores the necessity of size-specific occupational exposure limits for ITO nanoparticles and provides a mechanistic foundation for risk assessment and management strategies in occupational settings.
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高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2026
·
IF 8
Daohui Gong,Zhihao Zhu,Heng Qin,Mingzhou Zhang,Wen Zhang,Qing Xiang,Hang Qian,Binfeng He,Rong Zhang,Guansong Wang
Macrophage ferroptosis contributes to sepsis-associated acute lung injury (ALI); however, its upstream regulatory mechanisms remain poorly understood. Here, using a cecal ligation and puncture (CLP) murine sepsis model, we observed that macrophages from septic mice and bone marrow-derived macrophages (BMDMs) exposed to septic bronchoalveolar lavage fluid (BALF) exhibited concurrent suppression of EPOR expression and induction of ferroptosis. EPOR deficiency selectively reduced basal GPX4 expression and amplified ferroptotic cell death upon challenge with RSL3 or septic BALF. EPOR M−/− mice showed exacerbated sepsis-induced lung injury and mortality, which were rescued by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Mechanistically, EPOR deficiency downregulated PPARγ, which promotes GPX4 expression. EPOR deficiency also impaired PINK1-mediated mitophagy by reducing PINK1 but not PARKIN levels, while mitophagy induction attenuated ferroptosis in EPOR-deficient cells. rhEPO stimulation enhanced the EPOR/PPARγ axis and suppressed lipid peroxidation, whereas PPARγ antagonism inhibited PINK1 expression. We further identified Rab26 as a critical stabilizer of EPOR. Specifically, Rab26 deficiency upregulated the expression of BTRC, an E3 ligase that interacts with EPOR to promote its degradation. Consequently, Rab26 deficiency decreased EPOR levels, subsequently suppressing PPARγ and PINK1, thereby reducing GPX4 expression and blunting rhEPO-induced PINK1 upregulation. Collectively, EPOR signaling protects macrophages from ferroptosis by activating PINK1-mediated mitophagy in a Rab26-dependent manner. The Rab26-EPOR-PPARγ axis represents a promising therapeutic target for sepsis-induced lung injury.
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PubMed
高影响因子
Biomaterials Research
·
2026
·
IF 9.8
Jinzhuo Ning,Kun Jiang,Haoyong Li,Fan Cheng
Prostate cancer therapy is hindered by treatment resistance and an immunosuppressive microenvironment. To address this, we developed an innovative bimetallic nanozyme, Fe/Zn-CNZ@LOx@PEG, that integrates catalytic activity with metabolic and immune modulation. This nanoplatform executes a novel “metabolic-immuno” co-regulation strategy. Its Fe–Zn catalytic sites drive a lactate-fueled cascade reaction within the acidic tumor milieu, generating a burst of cytotoxic hydroxyl radicals. Simultaneously, released zinc ions rectify tumor zinc deficiency, disrupting cellular metabolism and promoting ferroptosis—an iron-dependent cell death—through glutathione depletion and lipid peroxidation. This ferroptotic cell death, in turn, acts as a potent trigger for immunogenic cell death (ICD), stimulating dendritic cell maturation and cytotoxic T cell infiltration to reverse immunosuppression. Consequently, Fe/Zn-CNZ@LOx@PEG demonstrates potent tumor suppression and effectively enhances the efficacy of anti-PD-1 therapy in a prostate cancer mouse model. This work presents a catalytic nanoreactor that co-regulates metabolism and immunity, offering a robust and synergistic strategy for the ferroptosis-immunotherapy of advanced cancers.
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PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Liang Feng,Huan Wang,Zuodi Liang,Ying Tian,Yang Guo,Zhuo Li
This study focused on developing a novel nanodelivery system, BP-PEG-S2P@H, with hesperetin-loaded black phosphorus nanosheets to target tumor-associated macrophages (TAMs) in triple-negative breast cancer (TNBC). Through RNA sequencing and proteomic analyses, CEBPG upregulation was observed in TAMs, potentially controlling the SLC7A11-mediated ferroptosis pathway. In vitro and in vivo experiments, including FerroOrange and malondialdehyde assays, demonstrated the induction of ferroptosis by BP-PEG-S2P@H. The nanoplatform facilitated the transition of TAMs from the M2 to the M1 subtype, enhancing IL-12 secretion while reducing IL-10 levels. Functional analyses confirmed the reversal of the pro-migratory TAM phenotype and inhibition of tumor cell invasion. In vivo imaging validated efficient tumor targeting, with immunohistochemical staining revealing decreased CEBPG/SLC7A11 expression in tumors, reduced macrophage infiltration, and enhanced CD8 + T cell activation, promoting the efficacy of PD-L1 immunotherapy. Biosafety assessments indicated no apparent toxicity, supporting the potential of the BP-PEG-S2P@H nanoplatform for TAM-targeted nano-immunotherapy in TNBC.
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PubMed
高影响因子
AQUACULTURE
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2026
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IF 4.4
Dianyang Zhou,Longdi Wang,Ping Han,Yadong Xue,Xiumei Liu,Jianming Chen,Daoquan Ren,Shengjie Ren,Xubo Wang
Alkaline stress is an important environmental factor in saline-alkaline aquaculture, yet its effects on marine euryhaline fish remain poorly understood. In this study, a multi-timepoint acute alkaline stress model was established to investigate hepatic responses in black sea bream ( Acanthopagrus schlegelii ). Fish in both control and treatment groups were maintained at a consistent salinity of 18‰, while the treatment group was exposed to 30 mmol/L NaHCO₃. Liver samples were collected at 0, 6, 12, 24, and 48 h post-exposure for histological, biochemical, and transcriptomic analyses. Alkaline stress induced progressive liver injury, characterized by hepatocellular ballooning, steatosis, and significant increases in ALT and AST activities. Oxidative stress and inflammatory responses were markedly activated, as indicated by altered redox balance, increased lipid peroxidation, and upregulation of pro-inflammatory cytokines. Transcriptomic analysis revealed dynamic changes in gene expression, with significant enrichment of pathways related to metabolism, immune response, and ferroptosis. Notably, ferroptosis-related pathways were consistently enriched, with marked alterations in ACSL4 and GPX4 protein abundance suggesting that ferroptosis-related pathways may be involved inalkaline-induced liver injury. These findings provide new insights into the molecular mechanisms linking oxidative stress, inflammation, and ferroptosis-related responses during alkaline stress adaptation in marine euryhaline fish.
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高影响因子
Biomaterials Advances
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2026
·
IF 6.7
Yong Zheng,Yong Tao,Fuqiang Tan,Keyi Feng,Fei Xie,Shasha Shi,Yunsheng Ou
In vitro : CPP reduced 143B cell viability by ~50% at 30 µg/mL with low toxicity to normal osteoblasts. • In vivo : CPP reduced xenograft tumor volume by ~80% and showed good biosafety in histology and serum tests. • Mechanism: CPP induced ROS accumulation, GSH depletion, SLC7A11/GPX4 downregulation, and ferroptotic mitochondrial damage. Ferroptosis induction represents a promising antitumor strategy, yet osteosarcoma cells frequently resist ferroptosis through the PSMD14-mediated stabilization of SLC7A11. Here, we report an acid-responsive cobalt-doped ZIF-8 nanoplatform loaded with 1, 10-phenanthroline and coated with PEG (denoted as CPP) that simultaneously amplifies oxidative stress and dismantles the PSMD14/SLC7A11 antioxidant axis. Upon exposure to the acidic tumor microenvironment, the ZIF-8 framework degrades, releasing Co 2+ ions that catalyze Fenton-like reactions to generate hydroxyl radicals (•OH) and initiate lipid peroxidation. Concurrently, 1, 10-phenanthroline chelates the catalytic Zn 2+ of PSMD14, abolishing its deubiquitinase activity and thereby promoting ubiquitin-dependent degradation of SLC7A11, which depletes intracellular glutathione (GSH). Physicochemical characterization confirmed the successful construction of CPP nanoparticles (~100 nm) with a drug loading efficiency of 14.76% and pH-triggered Co 2+ release. In vitro , CPP was efficiently internalized by 143B osteosarcoma cells and exhibited dose-dependent cytotoxicity with markedly elevated reactive oxygen species (ROS), malondialdehyde (MDA) accumulation, lipid peroxidation, mitochondrial depolarization, and downregulation of SLC7A11 and GPX4, collectively supporting ferroptosis. CPP also significantly suppressed osteosarcoma cell invasion. In a subcutaneous 143B xenograft model, intravenous CPP administration reduced tumor volume by approximately 80% relative to controls, with pronounced tumor necrosis, proliferation inhibition, and decreased SLC7A11/GPX4 expression in tumor tissues, while maintaining favorable biosafety. These findings establish CPP as a dual-action nanoplatform for ferroptosis-based osteosarcoma therapy.
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PubMed
高影响因子
TISSUE & CELL
·
2026
·
IF 3.1
Mingyue Zhang,Huichong Xu,Kaiwen Sun,Shuai Zhang,Shengnan Wang,Liqi Lin,Hongyu Li,Ying Hu
Ano5 loss alleviates osteoporosis by inhibiting osteoclastogenesis in OVX mice. • Ano5 deficiency triggers osteoclast ferroptosis by upregulating ACSL4 protein. • The Ano5 -ACSL4-ferroptosis axis is a therapeutic target for osteoporosis. Osteoporosis is driven by a pathological imbalance in bone remodeling, with osteoclast hyperactivation being a primary driver of bone loss. However, the intrinsic signaling nodes that govern osteoclast survival and function remain poorly understood. While loss-of-function mutations in Anoctamin 5 ( Ano5 ) are associated with genetic skeletal disorders, its precise involvement in metabolic osteoporosis remains elusive. In this study, we utilized an Ano5 -deficient ovariectomized (OVX) mouse model to investigate the role of Ano5 in bone homeostasis. We found that genetic depletion of Ano5 significantly attenuated the osteoporotic phenotype in OVX mice, evidenced by preserved bone microarchitecture, enhanced biomechanical properties, and suppressed bone resorptive activity. Mechanistically, Ano5 -deficient osteoclasts exhibited classical hallmarks of ferroptosis, including the accumulation of the lipid peroxidation end-product malondialdehyde (MDA), elevated reactive oxygen species (ROS), and a notable upregulation of the key lipid metabolic enzyme ACSL4 at the protein level. Importantly, the impaired osteoclastogenesis observed in Ano5 -deficient cells was effectively rescued by pharmacological inhibition of either ferroptosis (via Ferrostatin-1) or ACSL4 activity (via Rosiglitazone), which restored TRAP-positive osteoclast numbers, F-actin ring formation, and the expression of resorptive markers such as CTSK. Our findings identify Ano5 as a critical regulator of bone remodeling that modulates osteoclastogenesis through the ACSL4-dependent ferroptosis pathway. This study not only uncovers a previously unrecognized molecular axis in bone cell biology but also highlights the Ano5 -ACSL4-ferroptosis axis as a potential therapeutic target for the treatment of osteoporosis.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 6
Shiting Xu,Wenhao Gao,Shuang Lin,Shifan Xu,Xiaoting Shi,Da Zheng,Zhihong Liu,Lingjun Zeng,Aiwen Huang,Hongtao Song,Linlin Liu
Ferroptosis, a newly identified form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a promising therapeutic strategy for triple-negative breast cancer (TNBC) due to the heightened susceptibility of TNBC cells to this form of cell death. Nonetheless, the unique hypoxic and acidic tumor microenvironment confers resistance to ferroptosis, which limits the clinical efficacy of single-agent ferroptosis inducers. To overcome this, we developed a synergistically enhancing ferroptosis nanomedicine named sorafenib (SOR)-quercetin (QUE) nanoparticles (SQ NPs) by co-assembling SOR, QUE, and polyvinylpyrrolidone K30 (PVP K30). In this system, SOR facilitates ferroptosis by downregulating the expression of glutathione peroxidase 4 (GPX4). Simultaneously, QUE mitigates the hypoxic tumor microenvironment by suppressing the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and hexokinase Ⅱ (HK-Ⅱ), thereby inhibiting glycolysis, reducing LA production, and impeding GSH synthesis. This multifaceted approach culminates in enhanced ferroptosis in TNBC cells. In vivo studies on antitumor and antimetastatic effects have demonstrated the superior therapeutic efficacy and metastasis-inhibiting capabilities of SQ NPs in the context of TNBC. This report highlights the therapeutic potential of QUE in synergy with SOR under hypoxic conditions, offering a novel strategic approach for the treatment of TNBC.
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高影响因子
EXPERIMENTAL NEUROLOGY
·
2026
·
IF 4.8
Zhenyu Wu,Xufang Huo,Yubing Huang,Taowu Gong,Pengcheng Zhao,Yuhang Zhu,Qingfan Zeng
Although hypertension (HYP) consistently predicts cognitive decline, the precise pathogenic cascade within the brain remains elusive. Here we interrogated whether the PPARγ/ACSL3 axis governs HYP-elicited hippocampal ferroptosis and consequent cognitive dysfunction. This study aimed to explore the role of the PPARγ/ACSL3 axis in HYP-induced neuronal ferroptosis and cognitive impairment. In the HYP rat model, behavioral tests (Morris water maze and Y-maze tests) demonstrated that rats in the hypertensive group had a significant decline in learning and memory. Mechanistically, the AngII-AT1R axis was found to be activated in the hippocampus, accompanied by typical ultrastructural features of ferroptosis, increased iron accumulation, elevated oxidative stress, and downregulation of PPARγ, ACSL3, and key ferroptosis defense proteins (GPX4, XCT, and FPN1). In vitro, ACSL3 overexpression alleviated AngII-induced neuronal ferroptosis. Furthermore, the PPARγ agonist rosiglitazone attenuated lipid peroxidation and iron overload by transcriptionally upregulating ACSL3, a direct regulatory relationship confirmed by dual-luciferase reporter assay. In conclusion, under hypertensive conditions, BRAS activation inhibits the PPARγ/ACSL3 axis via the AngII-AT1R pathway, aggravates lipid peroxidation and ferroptosis in hippocampal neurons, and ultimately contributes to cognitive decline. This study provides new experimental evidence for the mechanism research and therapeutic target exploration of HYP-related cognitive impairment.
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产品关联
DOI
PubMed
高影响因子
Redox Biology
·
2026
·
IF 16.2
Yan Chen,Bo Zhang,Yufan Wei,Yanfa Dai,Baoyue Zhang,Jing Li,Ke-Jia Wu,Ning Sun,Chenwen Shao
Doxorubicin (DOX)-induced cardiotoxicity remains a major limitation of cancer chemotherapy, largely due to the lack of sensitive approaches for early detection and effective cardioprotective interventions. This study investigated whether cysteine depletion represents an early redox event during DOX cardiotoxicity and evaluated a cysteine-activatable fluorescent probe, termed the cardiotoxicity-responsive cysteine probe (CCP), for in vivo redox imaging and therapeutic discovery. Cardiac imaging revealed a significant reduction in intracellular cysteine levels three weeks after DOX administration, preceding systolic dysfunction detected by echocardiography at four weeks. Mechanistically, cysteine depletion was accompanied by impaired glutathione-dependent antioxidant defense, iron accumulation, lipid peroxidation, and ferroptosis. Through probe-guided screening, gnetol (a naturally occurring polyphenolic stilbene) was identified as a potent regulator of intracellular cysteine homeostasis. Gnetol restored cysteine and glutathione levels, reduced lipid peroxidation, and suppressed ferroptosis by modulating the SMAD–hepcidin–FPN1 axis and preserving glutathione peroxidase 4 activity. In the mouse model of DOX-induced cardiomyopathy, gnetol significantly improved cardiac function, attenuated myocardial injury and fibrosis, and reduced oxidative stress without evident systemic toxicity. Collectively, these findings establish cysteine depletion as an early redox feature of DOX cardiotoxicity and demonstrate that cysteine-targeted redox imaging enables mechanism-guided discovery of cardioprotective agents. This study highlights gnetol as a promising ferroptosis-suppressing candidate and provides a mechanistic framework for early detection and intervention in redox-driven cardiac injury.
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高影响因子
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