SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2023
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IF 4.4
Yiran Che,Jingying Yang,Zhenming Dong,Jianhua Wang,Xiaoqing Yan,Yu Wang,Shaomin Shuang
A novel Schiff-base fluorescent probe, 4-(N-(2- hydroxyl-1-naphthalymethylimino)-ethylamino) −7-nitro-1,2,3-benzoxadiazole (HENB) was synthesized and utilized for spectral sensing of Fe 3+ ions at neutral pH. The binding of Fe 3+ to HENB in C 2 H 5 OH-HEPES buffer (1:1 v/ v, 25 mM, pH 7.2) resulted in a pronounced emission enhancement at 530 nm, which is possibly due to the inhibition of photo-induced electron transfer (PET) process as well as the chelation enhanced fluorescence (CHEF) effect. HENB shows good selectivity and sensitivity toward Fe 3+ with the detection limit as low as 4.51 nM. Test strips made of HENB was used for rapid “naked-eye” detection of Fe 3+ ions in aqueous medium. Moreover, HENB was successfully applied in fluorescence imaging of exogenous and endogenous Fe 3+ in live Hela cells as well as zebrafish. Importantly, HENB is capable of effectively monitoring the variations of Fe 3+ in living cells during ferroptosis process.
研究领域:
分析化学
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生物医学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
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2023
·Vol. 18
·期 1
·1-15
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IF 2.6
Xue Xiang,Dai Tianming,Chen Junyan,Xu Yangyang,Yang Zhenyu,Huang Jian,Xu Wuyan,Li Siming,Meng Qingqi
Background Osteoarthritis (OA) is a prevalent disease plaguing the elderly. Recently, chondrocyte ferroptosis has been demonstrated to promote the progression of OA. Peroxisome proliferator-activated receptor-γ (PPARγ) is an important factor in maintaining cartilage health. However, the relationship between PPARγ and chondrocyte ferroptosis in OA and its mechanism is completely unclear.Methods We established a surgically induced knee OA rat model to investigate PPARγ and chondrocyte ferroptosis in OA. Rat knee specimens were collected for Safranin O/Fast Green staining and immunohistochemical staining after administered orally placebo or pioglitazone (PPARγ agonist) for 4 weeks. We used RSL3 to establish a chondrocyte ferroptosis model cultured in vitro to study the role of PPARγ activation toward ferroptosis, mitochondrial function, and PTEN-induced putative kinase 1 (Pink1)/Parkin-dependent mitophagy. GW9662 (PPARγ antagonist), Mdivi-1 (mitophagy inhibitor), and chloroquine (mitophagy inhibitor) were employed to investigate the mechanism of PPARγ-Pink1/Parkin-dependent mitophagy in the inhibition of ferroptosis.Results We found that PPARγ activation by pioglitazone attenuated not only OA but also inhibited the expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 (ACSL4) at the same time in rats. Furthermore, in vivo and in vitro data indicated that PPARγ activation restored Pink1/Parkin-dependent mitophagy, improved mitochondrial function, inhibited chondrocyte ferroptosis, and delayed the progression of OA.Conclusion sThe present study demonstrated that PPARγ activation attenuates OA by inhibiting chondrocyte ferroptosis, and this chondroprotective effect was achieved by promoting the Pink1/Parkin-dependent mitophagy pathway.
研究领域:
骨科
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Redox Biology
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2024
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IF 10.7
Yue-Yue Guo,Nan-Nan Liang,Xiao-Yi Zhang,Ya-Hui Ren,Wen-Zheng Wu,Zhi-Bing Liu,Yi-Zhang He,Yi-Hao Zhang,Yi-Chao Huang,Tao Zhang,De-Xiang Xu,Shen Xu
Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD + -dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3 −/− mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.
研究领域:
毒理学
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肾脏生理学
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细胞生物化学
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2025
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IF 5.5
Xiaoli Bao,Xiuqing Liao,Zhongqiang Zhu,Ling Jiang,Daoxin Wang
Acute lung injury (ALI) represents a life-threatening condition with limited therapeutic options. Emerging evidence suggests that ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation, is a key pathological mechanism underlying ALI. Therefore, we systematically investigated the key role of ferroptosis in ALI pathogenesis using a lipopolysaccharide (LPS)-induced mouse model of sepsis-related ALI. Based on this finding, we engineered polyvinylpyrrolidone-assembled cobalt hexacyanoferrate nanocatalysts (CoHCF NCs) as a ferroptosis inhibitor. These nanocatalysts exhibited dual functions: efficient chelation of free iron ions and strong antioxidant activity. In vivo experiments showed the promising therapeutic efficacy of CoHCF NCs, while in vitro studies using erastin-induced ferroptosis in alveolar epithelial cells confirmed their strong ability to reverse ferroptotic processes. To explore the underlying mechanisms, we employed RNA sequencing, which revealed that CoHCF NCs exert their antiferroptotic effects through a transcriptional network involving antioxidant response enhancement, and iron ion homeostasis regulation. Due to their high ferroptosis-inhibitory capacity and biocompatibility, CoHCF NCs represent a promising therapeutic candidate for ALI.
研究领域:
呼吸病学
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纳米医学
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分子病理学
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氧化应激
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重症医学
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药理学
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细胞生物学
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产品关联
DOI
高影响因子
Advanced Science
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2024
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IF 14.3
Zhizhao Deng,Weiqi Zeng,Yingxin Gao,Zhenyu Yang,Xinling Luo,Xianlong Li,Guoliang Sun,Erfeng Xiong,Fei Huang,Gangjian Luo,Ziqing Hei,Dongdong Yuan
Ischemia-reperfusion injury (IRI) is the leading cause of hepatic graft dysfunction, resulting from hepatocyte damage. Nevertheless, given the few specialized therapeutics available in hepatic IRI, additional mechanistic insights into hepatocyte damage are required. Here, the protein solute carrier family 39 member 14 (SLC39A14) is identified as a pro-ferroptosis target in hepatocytes of human liver allografts through single-cell RNA sequencing analysis. SLC39A14 knockdown significantly mitigated hepatic IRI by preventing hepatocyte ferroptosis in vivo and in vitro. Mechanistically, the inhibition of SLC39A14 suppressed non-transferrin-bound iron (NTBI) uptake by hepatocytes, thereby reducing iron overload and cell ferroptosis. Moreover, human bone marrow-derived mesenchymal stem cells (hBMSCs) are found to exhibit a notable therapeutic effect on hepatic IRI by downregulating SLC39A14 expression. Exosomes derived from hBMSCs delivered abundant miR-16-5p into hepatocytes, which post-transcriptionally suppressed the expression of SLC39A14 and reduced cell ferroptosis induced by hepatic IRI. In conclusion, SLC39A14 triggers hepatic IRI by mediating NTBI uptake into hepatocytes and inducing hepatocyte ferroptosis. Moreover, hBMSC-based therapy is promising to reverse this progression of hepatic IRI.
研究领域:
干细胞治疗
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分子生物学
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肝病学
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器官移植
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DOI
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Yueqi Ni,Yuanyuan Hu,Lijia Zhu,Xulin Jiang,Hong Zhang,Jia Liu,Yin Zhao
Retinal ischemia‒reperfusion (IR) is a major contributor to vision impairment and irreversible vision loss due to retinal ganglion cell (RGC) injury or loss. Contemporary therapeutic approaches predominantly focus on the amelioration of symptoms rather than addressing the fundamental etiological factors. Oxidative stress is a notable feature and an important mediator of IR damage. Lycium barbarum polysaccharide (LBP), the main active ingredient of Lycium barbarum, has various pharmacological effects, including antioxidation, immunoregulation, and neuroprotective effects. In this study, the ROS-consumable moiety phenylboronic acid pinacol ester (PBA) is introduced to LBP molecules, which can self-assemble into nanoparticles in aqueous solution. This nanoparticle (termed PLBP) can reduce the cellular ROS levels and enhance the antioxidant capability of RGCs by activating the NRF2 pathway, thus protecting RGCs from ferroptosis and preserving visual function in response to IR injury. PLBP also reduces neuroinflammation by inhibiting the ability of microglia to phagocytose, migrate, secrete inflammatory cytokines, and activate the NF-κB pathway. In conclusion, this approach can be used as an inspiration for the future development of neuroprotective drugs.
研究领域:
眼科学
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神经科学
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药理学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2023
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IF 15.1
Xinyu Miao,Yinyan Yin,Yulian Chen,Wenhui Bi,Yuncong Yin,Sujuan Chen,Daxin Peng,Lizeng Gao,Tao Qin,Xiufan Liu
Influenza virus with numerous subtypes and frequent variation limits the development of high-efficacy and broad-spectrum antiviral strategy. Here, a novel multi-antiviral metastable iron sulfides (mFeS) against various influenza A/B subtype viruses is developed. This work finds that mFeS induces high levels of lipid peroxidation and •OH free radicals in the conservative viral envelope, which depends on Fe 2+ . This phenomenon, termed as a viral ferroptosis, results in the loss of viral infectibility and pathogenicity in vitro and in vivo, respectively. Furthermore, the decoction of mFeS (Dc(mFeS)) inhibits cellular ferroptosis-dependent intracellular viral replication by correcting the virus-induced reprogrammed sulfur metabolism, a conserved cellular metabolism. Notably, personal protective equipment (PPE) that is loaded with mFeS provides good antiviral protection. Aerosol administration of mFeS combined with the decoction (mFeS&Dc) has a potential therapeutic effect against H1N1 lethal infection in mice. Collectively, mFeS represents an antiviral alternative with broad-spectrum activity against intracellular and extracellular influenza virus.
研究领域:
病毒学
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药理学
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材料科学
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治疗学
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产品关联
DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
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2024
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IF 1.9
Lin Shuai,Cai Hui,Song Xuemei
The objective of this study was to explore the effects and mechanisms of the combination of isobavachalcone (IBC) and doxorubicin (DOX) on the progression of anaplastic thyroid cancer (ATC). Cell viability of 8505C and CAL62 cells was observed by CCK-8 assay. Kits were used to detect the presence of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and cellular iron. Protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was detected using western blot, and CD31 was detected through immunofluorescence. Tumor xenograft models of 8505C cells were constructed to observe the effect of IBC and DOX on ATC growth in vivo. The co-administration of IBC and DOX exhibited a synergistic effect of suppressing the growth of 8505C and CAL62 cells. The concurrent use of IBC and DOX resulted in elevated iron, ROS, and MDA levels, while reducing GSH levels and protein expression of SLC7A11 and GPX4. However, the Fer-1 ferroptosis inhibitor effectively counteracted this effect. In vitro and in vivo, the inhibitory effect on ATC cell proliferation and tumor growth was significantly enhanced by the combination of IBC and DOX. The combination of IBC and DOX can inhibit the growth of ATC by activating ferroptosis, and might prove to be a potent chemotherapy protocol for addressing ATC.
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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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Peipei Cheng,Xinting Wang,Qian Liu,Tianshu Yang,Enrui Dai,Wanjing Sha,Huiyan Qu,Hua Zhou
ABSTRACT Background The terminal stage of all cardiovascular diseases typically culminates in heart failure (HF), with no effective intervention available to halt its progression. LuQi formula (LQF) has been employed in clinical for numerous years to significantly ameliorate cardiac function in HF patients. Nevertheless, the underlying mechanism of LQF's efficacy remains inadequately comprehended. Cardiomyocyte ferroptosis has served as a pathogenic mechanism in HF. The goal of the current experiment was to ascertain whether LQF ameliorates HF by preventing cardiomyocyte ferroptosis and to elucidate the intrinsic mechanism involved. Purpose This research objective is to investigate the impact and underlying mechanism of LQF attenuating cardiomyocyte ferroptosis in heart failure. Methods Transverse aortic constriction (TAC) was performed to construct the HF mouse model. Neonatal rat cardiomyocytes (NRCMs) were subjected to in vitro experiments. High-performance liquid chromatography (HPLC) identified the bioactive compounds in LQF. Transcriptomic and quantitative proteomic analyses revealed the potential targets of LQF anti-HF. Specifically, histological staining evaluated cardiac hypertrophy and fibrosis. Transmission electron microscopy (TEM) observed mitochondrial morphology. The content of Fe 2+ , ROS, MDA, GSH, and GSSH was detected using kits. Molecular docking evaluated the binding activities between essential active ingredients of LQF and critical proteins of cardiomyocyte ferroptosis. Mechanistically, the expression levels of Nrf2, Keap1, HO-1, SLC7A11, and GPX4 were evaluated using qPCR, Western blot (WB), or immunohistochemical staining. Results The primary nine active ingredients in LQF were detected. Transcriptomic and proteomic analyses demonstrated that LQF may ameliorate HF by preventing cardiomyocyte ferroptosis. Histomorphometric analyses revealed that LQF attenuates myocardial hypertrophy and fibrosis. TEM revealed that LQF diminished mitochondrial shrinkage and increased membrane density in myocardial tissue. Additionally, LQF diminished reactive oxygen species (ROS) generation in cardiomyocytes and suppressed cardiomyocyte ferroptosis. Furthermore, the molecular docking technique revealed that the primary active ingredients of LQF had suitable binding activities with Nrf2, GPX4, and SLC7A11. Western analysis further verified that LQF activated the Nrf2/GPX4 signaling axis. decreased SLC7A11 and HO-1 expression. Conclusions These results demonstrated that LQF prevents cardiomyocyte ferroptosis via activating Nrf2/GPX4 signaling axis and suppressing SLC7A11 and HO-1 expression. Concurrently, it contributed to elucidating the intrinsic mechanism of LQF and provided a scientific rationale for its development as a novel cardiovascular therapeutic drug.
研究领域:
心血管疾病
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药理学
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分子生物学
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细胞生物学
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信号转导
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产品关联
DOI
PubMed
高影响因子
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