MOLECULAR HUMAN REPRODUCTION
·
2023
·
IF 4
Dong Xiaoyu,Xu Le,Wang Shuang,Jiao Xue,Yan Shumin,Huang Yufei,Yuan Ming,Wang Guoyun
Ferroptosis is an iron-dependent programmed cell death process characterised by the accumulation of lethal oxidative damage. Localised iron overload is a unique clinical phenomenon in ovarian endometriosis. However, the role and mechanism of ferroptosis in the course of ovarian endometriosis remain unclear. Traditionally, autophagy promotes cell survival. However, a growing body of research suggests that autophagy promotes ferroptosis under certain conditions. This study aimed to clarify the status of ferroptosis in ovarian endometriosis and explore the mechanism(s) by which iron overload causes ferroptosis and ectopic endometrial resistance to ferroptosis in human. The results showed increased levels of iron and reactive oxygen species in ectopic endometrial stromal cells. Some ferroptosis and autophagy proteins in the ectopic tissues differed from those in the eutopic endometrium. In vitro, iron overload caused decreased cellular activity, increased lipid peroxidation levels, and mitochondrial morphological changes, whereas ferroptosis inhibitors alleviated these phenomena, illustrating activated ferroptosis. Iron overload increased autophagy, and ferroptosis caused by iron overload was inhibited by autophagy inhibitors, indicating that ferroptosis caused by iron overload was autophagy-dependent. We also confirmed the effect of iron overload and autophagy on lesion growth in vivo by constructing a mouse endometriosis model; the results were consistent with those of the in vitro experiments of human tissue and endometrial stomal cells. However, ectopic lesions in patients can resist ferroptosis caused by iron overload, which can promote cystine/glutamate transporter hyperexpression by highly expressing activating transcription factor 4 (ATF4). In summary, local iron overload in ovarian endometriosis can activate autophagy-related ferroptosis in endometrial stromal cells, and ectopic lesions grow in a high-iron environment via ATF4-xCT while resisting ferroptosis. The effects of iron overload on other cells in the endometriosis environment require further study. This study deepens our understanding of the role of ferroptosis in ovarian endometriosis.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Zhijing He,He Zhou,Qixiang Feng,Yu Zhang,Shan Gao,Shangui Liu,Lei Ye,Jianbo Ji,Yanwei Xi,Xiaoye Yang,Guangxi Zhai
Restricted by the complex intracellular ferroptosis regulatory networks, single ferroptotic therapy against breast cancer (BC) yields limited therapeutic outcomes. Therefore, novel combination modes are being widely attempted; however, the interactions between different treatments are still less studied. Herein, we propose a combinational pattern by constructing a novel nanoplatform (T-FeCo/P) composed of Panobinostat (histone deacetylase inhibitor)-loaded iron (Fe)/cobalt (Co)-based metal–organic framework with surface modification of telmisartan for dual 4 T1 cell/cancer-associated fibroblast (CAF) targeting. T-FeCo/P exhibits good photothermal performance and forcefully triggers cellular ferroptosis, and the dopant of Fe realizes stronger ferroptosis activation than the corresponding single-metal system. Interestingly, for the first time, Panobinostat is elucidated to promote ferroptosis by inhibiting SLC7A11 transcription and regulating thioredoxin binding protein 2 (TBP2)/thioredoxin (Trx) axis. For tumor microenvironment (TME) remodeling, T-FeCo/P specifically kills CAFs, thus destroying extracellular matrix and retarding C-X-C motif chemokine ligand 12 (CXCL12) secretion, which are beneficial to intratumoral drug penetration and cytotoxic T lymphocyte infiltration. Also, this CAF elimination probably sensibilizes ferroptosis by regulating neurofibromatosis type 2 (NF2)-yes associated protein (YAP) pathway and reducing myeloid-derived suppressor cell infiltration. Our experimental data support T-FeCo/P’s tumoricidal activity thanks to the combined ferroptosis activation, epigenetic regulation, photothermal therapy and TME re-education, providing a mighty pattern for BC treatment and constituting a substantial addition to ferroptosis sensitization.
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高影响因子
CELLULAR ONCOLOGY
·
2023
·
IF 6.6
Wei Wanhui,Lu Yuanyuan,Hu Qian,Yin Jinwen,Wang Youwei,Zhang Heng,Zhao Qiu,Liu Lan
Purpose The combination of cisplatin and gemcitabine-based chemotherapy has been recommended as a preferred regimen for pancreatic ductal adenocarcinoma (PDAC) patients with germline-based mutations. However, the underlying mechanism remains poorly elucidated. Therefore, our study aimed to explore the mechanistic basis of the cell-killing activity of gemcitabine plus cisplatin and identify potential therapeutic targets. Methods First, we explored the synergistic cytotoxic effects of gemcitabine and cisplatin on PDAC through in vitro and in vivo experiments. Then, we investigated ferroptosis-related biomarkers, to assess the impact of the combination therapy on ferroptosis. Using bioinformatics methods, we identified SAT1 as a potential key mediator of ferroptosis induced by gemcitabine and cisplatin. We tested the polyamine levels in PDAC cells by LC–MS after overexpressed or knocked down SAT1, and explored the role of polyamines in ferroptosis using exogenous supplementation. Finally, we explored the regulatory effect of Sp1 on SAT1 through ChIP-qPCR and dual-luciferase reporter assay. Results Gemcitabine plus cisplatin enhanced cell death and induced ferroptosis in PDAC. This combination upregulated SAT1 transcription by inhibiting Sp1. SAT1 activation promoted the catabolism of spermine and spermidine, leading to iron accumulation and lipid peroxide generation, ultimately resulting in ferroptosis. Conclusions In summary, our findings suggested the gemcitabine and cisplatin combination therapy induced ferroptosis in a GSH-independent manner in PDAC. The combined treatment inhibited Sp1 and upregulated SAT1 transcription, leading to the breakdown of spermine and spermidine. Therefore, targeting SAT1-induced polyamine metabolism may represent a promising therapeutic strategy for PDAC.
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高影响因子
FEBS Open Bio
·
2021
·Vol. 11
·期 8
·2118-2126
·
IF 2.693
Na Wei,Tan Lu,Libin Yang,Yonghan Dong,Xiaotan Liu
Ferroptosis is an iron-dependent programmed cell death, which participates in the pathogenesis of spinal cord injury (SCI). Our previous study has revealed that Lipoxin A4 (LXA4) exerts a protective role in SCI. Here, we investigated whether LXA4 can protect SCI through inhibiting neuronal ferroptosis. We treated primary spinal cord neurons with Erastin (ferroptosis activator) to induce ferroptosis. Erastin treatment reduced cell viability and enhanced cell death of primary spinal cord neurons, which was rescued by ferrostatin-1 (ferroptosis inhibitor). Moreover, Erastin repressed glutathione peroxidase 4 (GPX4) expression and the levels of glutathione and cysteine in primary spinal cord neurons. Erastin also enhanced the expression of ferroptosis biomarkers (PTGS2 and ACSL4) and the levels of reactive oxygen species (ROS) in primary spinal cord neurons. The influence conferred by Erastin was effectively abolished by LXA4 treatment. Furthermore, LXA4 enhanced the protein expression of p-AKT, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and haem-oxygenase-1 (HO-1) in primary spinal cord neurons. LXA4-mediated inhibition of ferroptosis of primary spinal cord neurons was prohibited by LY294002 (AKT inhibitor), brusatol (Nrf2 inhibitor) or zinc protoporphyrin (HO-1 inhibitor). In conclusion, this work demonstrated that LXA4 exerted a neuroprotective effect in Erastin-induced ferroptosis of primary spinal cord neurons by activating the Akt / Nrf2 / HO-1 signaling pathway. Thus, this work provides novel insights into the mechanisms of action of LXA4 in ferroptosis of primary spinal cord neurons and indicates that LXA4 may be a potential therapeutic agent for SCI.
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ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Mangmang Sang,Renjie Luo,Yidan Bai,Jun Dou,Zhongtao Zhang,Fulei Liu,Feng Feng,Wenyuan Liu
Ferroptosis is an iron-dependent cell death caused by accumulation of lipid peroxidation (LPO), which is a new strategy for cancer treatment. Th current ferroptosis therapy nanodevices have low efficiency and side effects generally. Hence, we developed a Black Hole Quencher (BHQ)-based fluorescence “off–on” nanophotosensitizer complex assembly (CSO-BHQ-IR780-Hex/MIONPs/Sor). CSO-connected BHQ-IR780-Hex and -loaded magnetic iron oxide nanoparticles (MIONPs) and sorafenib (Sor) formed a very concise functionalized delivery system. CSO-BHQ-IR780-Hex disassembled by GSH attack and released IR780-Hex, MIONPs, and sorafenib. IR780-Hex anchored to the mitochondrial membrane, which would contribute to amplifying the efficiency of the photosensitizer. When NIR irradiation was given to CSO-BHQ-IR780-Hex/MIONPs/Sor-treated cells, iron supply increased, the xCT/GSH/GPX-4 system was triggered, and a lot of LPO burst. A malondialdehyde test showed that LPO in complex assembly-treated cells was explosive and increased about 18-fold compared to the control. The accumulation process of particles was monitored by an IR780-Hex photosensitizer, which showed an excellent tumor target ability by magnetic of nanodevice in vivo. Interestingly, the half-life of sorafenib in a nanodevice was increased about 26-fold compared to the control group. Importantly, the complex assembly effectively inhibits tumor growth in the breast tumor mouse model. This work would provide ideas in designing nanomedicines for the ferroptosis treatment of cancer.
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CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Shuyun Zhang,Baihua Peng,Yong Qi,Changpeng Xu,Yan Wang,Tinghui Xian,Jie Huang,Lin Liang,Zhen Lin,Hao Wu,Lihua Li
Impaired mitochondrial autophagy and ferroptosis in Human Immortalized Epidermal Cells (HaCats), caused by oxidative stress, are significant obstacles to diabetic wound healing. However, research on the mechanistic level of skin repair through the improvement of mitochondrial function and inhibition of iron-induced cell death by natural-based hydrogel materials is still lacking. In this study, we engineered pH and glucose-responsive Hst1@CBTC hydrogels leveraging dynamic borate bonding, exhibiting an impressive peptide release rate of up to 90 ± 4.2 %. In both in vitro and in vivo settings, the administered peptide demonstrated remarkable efficacy in counteracting cellular mitochondrial autophagy dysfunction and iron-induced cellular demise within oxidative stress environments. Consequently, the hydrogel facilitated expedited healing of recalcitrant diabetic wounds, showcasing a commendable wound closure rate of 94.7 ± 5.1 % within a span of 14 days. Of significant note, our findings elucidate the potential of Hst1@CBTC in ameliorating the cellular ferroptotic milieu by activating the Nrf/HO-1 pathway, thereby fostering mitochondrial autophagy restoration. This study proposes a theoretical solution to address mitochondrial dysfunction and ferroptosis in an oxidative stress environment. Additionally, it presents a safe hydrogel made from natural biosafety materials.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Rongying Ma,Yufei Zhang,Hongting Ji,Huiling Fu,Shuzhen Gu,Qianhong Su,Yumian Lin,Qingchun Deng,Wei Xue,Yong Yang
Nanocarriers responding to tumor microenvironment have been extensively exploited to improve the antitumor outcome of chemotherapeutic drugs. However, selectively and completely releasing drugs within the tumor remains a challenge, thereby limiting the therapeutic effect of drug delivery nanosystem. To tackle this challenge, a metal-phenolic networks (MPNs)-based nanosystem (F-MGD) showing the capability of self-accelerating drug release was originally fabricated in this study. Glucose oxidase (GOx) encapsulated in F-MGD could conduct the glucose transformation in tumor to cause the oxygen consumption and the production of gluconic acid and H 2 O 2 . Therefore, F-MGD with acid and hypoxia sensitivities thoroughly disintegrated under the aggravated acidity and hypoxia to achieve a more complete drug release. Besides, the product of H 2 O 2 was readily decomposed into hydroxyl radicals via the iron ion-mediated Fenton reaction, which markedly augmented the oxidative stress in tumor cells and promoted ferroptosis. The results of both in vitro and in vivo assays demonstrated the significant antitumor efficacy of F-MGD. Collectively, this study proposes a strategy to expedite drug release in tumor and improve the tumor treatment effect by combining ferroptosis-based therapy and chemotherapy.
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ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Wenhui Xie,Yilin Lu,Yilin Yuan,Lulu Xiao,Jiaqi Liu,Haofeng Song,Rongcheng Niu,Yanli Liu,Juntang Lin
Metal peroxide nanomaterials as efficient hydrogen peroxide (H2O2) self-supplying agents have attracted the attention of researchers for antitumor treatment. However, relying solely on metal peroxides to provide H2O2 is undoubtedly insufficient to achieve optimal antitumor effects. Herein, we construct novel hyaluronic acid (HA)-modified nanocomposites (MgO2/Pd@HA NCs) formed by decorating palladium nanoparticles (Pd NPs) onto the surfaces of a magnesium peroxide (MgO2) nanoflower as a highly effective nanoplatform for the tumor microenvironment (TME)-responsive induction of ferroptosis in tumor cells and tumor photothermal therapy (PTT). MgO2/Pd@HA NC could be well endocytosed into tumor cells with CD44 expression depending on the specific recognition of HA with CD44, and then, the nanocomposites can be rapidly decomposed in mild acid and hyaluronidase overexpressed TME, and plenty of H2O2 was released. Simultaneously, Pd NPs catalyze self-supplied H2O2 to generate abundant hydroxyl radicals (•OH) and catalyze glutathione (GSH) into glutathione disulfide owing to its peroxidase and glutathione oxidase mimic enzyme activities, while the abundant •OH could also consume GSH in tumor cells and disturb the defense pathways of ferroptosis leading to the accumulation of lipid peroxidation and resulting in the occurrence of ferroptosis. Additionally, the superior photothermal conversion performance of Pd NPs in near-infrared II could also be used for PTT, synergistically cooperating with nanocomposite-induced ferroptosis for tumor inhibition. Consequently, the successfully prepared TME-responsive MgO2/Pd@HA NCs exhibited marked antitumor effect without obvious biotoxicity, contributing to thoroughly explore the nanocomposites as a novel and promising treatment for tumor therapy.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Guanhua Qiu,Duo Wang,Peihan Xie,Zelun Li,Niqiang Zhou,Xiaoqian Zhang,Xiaobo Wang,Jiali Tang,Jun Cao,Junjie Liu,Danke Su
Microwave ablation (MWA) holds promise as a tumor treatment modality, yet incomplete ablation with low-frequency MWA (iMWA) remains a significant obstacle to survival, while the high-frequency MWA poses safety concerns. To address these challenges, we introduce a novel bimetallic iMWA nanosensitizer, CFT-NPs, constructed via metal-coordination interactions between tannic acid (TA) and iron/calcium dual metal ions (Fe 3+ /Ca 2+ ). The Fe 3+ /Ca 2+ in CFT-NPs work in harmony to convert electromagnetic energy into heat, thereby bolstering the effectiveness of iMWA while maintaining good biosafety. Furthermore, the pH-triggered rupture of CFT-NPs release TA, Fe 3+ , and Ca 2+ . The liberated Fe 3+ undergoes reduction by TA, and when combined with Ca 2+ , they trigger ferroptosis and Ca 2+ overload respectively, significantly amplifying the therapeutic effects of iMWA. Utilization iMWA with CFT-NPs results in lipid oxidation, mitochondrial dysfunction, and disruption of redox balance, both in vitro and in vivo . Notably, this nanosensitizer exerts a robust antitumor effect, effectively inhibiting tumor growth and downregulating the expression of matrix metalloproteinases, which is associated with tumor metastasis. Collectively, this innovative study offers a promising approach to overcome the challenges of incomplete ablation and biological safety, enhancing the antitumor efficacy of iMWA..
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Advanced Science
·
2024
·
IF 14.3
Yu Li,Hongji Li,Keying Zhang,Chao Xu,Jingwei Wang,Zeyu Li,Yike Zhou,Shaojie Liu,Xiaolong Zhao,Zhengxuan Li,Fa Yang,Wei Hu,Yuming Jing,Peng Wu,Jingliang Zhang,Changhong Shi,Rui Zhang,Wenkai Jiang,Nianzeng Xing,Weihong Wen,Donghui Han,Weijun Qin
Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration-resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron-dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate-specific membrane antigen (PSMA)-targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane-coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M-gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA-specific, CRPC-targeting platform for ferroptosis induction with increased efficacy and safety.
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高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Wang Haoyue,Sun Kexiang,Tan Wei Shan,Gao Jiamin,Yuan Luyun,Wen Junkai,Deng Wanli
Background A controlled type of cell death called ferroptosis is linked to increased reactive oxygen species (ROS), lipid peroxidation, and iron buildup. Furthermore, evidence indicates that ferroptosis may act as an immunogenic form of cell death with potential physiological functions in tumors and immunosuppression. Inducing ferroptosis in tumor cells may have the potential to complement cancer immunotherapy strategies. The development of colorectal cancer (CRC) and the poor efficacy of immunotherapy are associated with the crosstalk of cellular ferroptosis. Currently, Icariin (ICA), the main bioactive component extracted from Epimedium , has been shown to inhibit a variety of cancers. However, the specific role and potential mechanism of ICA in regulating ferroptosis in CRC remains unclear. Purpose The aim of this investigation was to clarify the mechanism underlying the anti-CRC cancer properties of ICA and how it induces ferroptosis to enhance immunotherapy. Methods To evaluate cell viability, the Cell Counting Kit-8 (CCK-8) test was utilized. The transwell test and the wound healing assay were used to assess cell migration. A subcutaneous graft tumor model was constructed with C57BL/6 mice using MC38 colorectal cancer cell lines. The inhibitory effect of ICA on CRC, ferroptosis level and immunomodulatory effects were detected by serum biochemical assay, cytokine assay, hematoxylin-eosin (H&E) staining, immunofluorescence staining, CyTOF mass spectrometry flow screening and Western blotting. Western blotting, proteomics, molecular docking and microscale thermophoresis (MST) were used to forecast and confirm ICA's binding and interaction with HMGA2, STAT3, and HIF-1α. Moreover, the levels of lipid peroxidation and ferroptosis were assessed through the use of the C11-BODIPY fluorescent probe, the FerroOrange fluorescent probe, the iron level, the malondialdehyde (MDA) and reduced glutathione (GSH) assay kit, and Western blotting analysis. To assess alterations in mitochondrial structure and membrane potential, transmission electron microscopy (TEM) and JC-1 immunofluorescence were employed. Results It was demonstrated in the current study that ICA treatment inhibits CRC and enhances anti-PD-1 therapy efficacy by inciting ferroptosis. As shown in vitro, ICA inhibits CRC cell proliferation, migration, and apoptosis. As demonstrated in vivo, ICA has a dose-dependent tumor suppressor effect when combined with anti-PD-1, it can significantly inhibit tumor growth, increase the expression of serum TNF-α, IFN-γ, and granzyme B, and promote CD69 + CD8 + T, CD69 + CD8 + Tem, CD69 + CD8 + Teff, TCRβ + CD8 + T, TCRβ + CD8 + T, TCRβ + CD8 + Tem, TCRβ + CD8 + Teff. The inhibitory effect of ICA on CRC was associated with the binding of HMGA2, STAT3, and HIF-1α proteins, which inhibited CRC by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), promoting the accumulation of iron (Fe 2+ ), depletion of reduced glutathione (GSH), inhibiting SLC7A11 and GPX4 expressions, thereby inducing ferroptosis in CRC. As a consequence of ICA-induced ferroptosis, mitochondria are dysfunctional, with increased ROS production, membrane potential depolarization (MMP), and ATP production reduced. This process can be efficiently reversed by the mitochondria-targeted antioxidant Mito-Q. It is noteworthy that the ferroptosis inhibitor liproxstatin-1 (lip-1), anti-CD8, and anti-IFN-γ exhibited a significant inhibitory effect on the level of ferroptosis and antitumor capacity of ICA combined with anti-PD-1. This finding suggests that the antitumor immunopotentiating effect of ICA on anti-PD-1 is dependent on the secretion of IFN-γ-induced ferroptosis of CRC cells by the CD8 + T cell. Conclusion Our study represents the inaugural demonstration of the mechanism whereby ICA exerts anti-CRC effects and synergistically enhances the efficacy of anti-PD-1, inducing mitochondrial damage and leading to ferroptosis. ICA promotes ferroptosis of CRC cells by inducing mitochondrial dysfunction, and ICA combined with anti-PD-1 significantly promotes CD69, TCRβ signalling, activates effector CD8 + T cells to secrete IFN-γ, and achieves immunopotentiation by promoting ferroptosis of CRC cells, thus inhibiting CRC development. This study is built upon existing research into the pharmacodynamic mechanisms of ICA in the context of CRC, and offers a novel therapeutic approach in addressing the issue of CRC immunotherapy potentiation.
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高影响因子
NEUROCHEMICAL RESEARCH
·
2025
·Vol. 50
·期 1
·1-17
·
IF 3.8
Min Xiao-li,Shi Ying,Xu Ying,Li Yu-ye,Dong You-kang,Chen Fei-xiong,Chen Quan-ming,Sun Yu-long,Liao Rui,Wang Jia-ping
Objective: Post-resuscitation brain injury is a common sequela after cardiac arrest (CA). Increasing sirtuin1 (SIRT1) has been involved in neuroprotection in oxygen-glucose deprivation (OGD) neurons, and we investigated its mechanism in post-cardiopulmonary resuscitation (CPR) rat brain injury by mediating p65 deacetylation modification to mediate hippocampal neuronal ferroptosis. Methods: Sprague-Dawley rat CA/CPR model was established and treated with Ad-SIRT1 and Ad-GFP adenovirus vectors, or Erastin. Rat postoperative neurological function, and cognitive and learning abilities were assessed by neurological deficit score and Morris water maze test. Hippocampal neuronal pathological changes and injury were evaluated by H&E and TUNEL staining. Serum brain injury biomarkers and hippocampal inflammatory factors and SIRT1 mRNA levels were determined by ELISA and RT-qPCR. OGD/reoxygenation (OGD/R) rat hippocampal neuron (H19-7) model was established. Cell viability and injury, nuclear factor-kappa B (NF-κB) p65 localization, iron content, and levels of glutathione, malondialdehyde, reactive oxygen species, SIRT1, Ac NF-κB p65 (Lys310), NF-κB p65, ACSL4, glutathione peroxidase 4 and SLC7A11 were measured. Results: In CA/CPR rats, SIRT1 was down-regulated, and SIRT1 overexpression alleviated cerebral injury. SIRT1 overexpression inhibited OGD/R-induced H19-7 cell ferroptosis to ameliorate cell injury, and inactivated the NF-κB pathway by reducing p65 acetylation to hinder its entry into the nucleus. Inactivating the NF-κB pathway reduced OGD/R-induced ferroptosis and alleviated cell injury. SIRT1 alleviated cerebral injury by mediating p65 deacetylation to inhibit hippocampal neuronal ferroptosis mediated by the NF-κB pathway. Conclusions: SIRT1 inhibited the NF-κB signaling pathway-mediated hippocampal neuronal ferroptosis by mediating p65 deacetylation modification, thereby alleviating brain injury in CA/CPR rats.
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