Science Advances
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2025
·Vol. 11
·期 11
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IF 12.5
Fuyuan Zheng,Xufeng Wan,Yangming Zhang,Yan Yue,Qiaochu Li,Zhuang Zhang,Shuoyuan Li,Hong Xu,Qiang Su,Xiaoting Chen,Le Tong,Long Zhao,Jian Cao,Xin Tang,Xiao Yang,Jiagang Wu,Jian Li,Xiang Lv,Zongke Zhou,Duan Wang
Tracking and eradicating drug-resistant bacteria are critical for combating implant-associated infections, yet effective antibacterial therapies remain elusive. Herein, we propose an oxygen vacancy–rich (BiFe)0.9(BaTi)0.1O3−x nanoreactor as a piezoelectric sonosensitizer by spatiotemporal ultrasound–driven sono- and chemodynamic tandem catalysis to amplify antibacterial efficacy. The piezoelectric charge carriers under a built-in electric field synchronize the reaction of O2 and H2O, efficiently generating H2O2. The electron-rich oxygen vacancies modulate the local electronic structure of an Fe site. It facilitates reactive oxygen species generation by piezoelectric electrons and accelerates valence state cycles of Fe(III)/Fe(II) to achieve the sustained maintenance of hydroxyl radicals via H2O2/Fe(II)–catalyzed chemodynamic reactions, which lead to bacterial membrane damage. Transcriptomics analysis revealed that intracellular Fe overload induced by excessive Fe(II)-mediated dysregulation of the two-component system disrupts bacterial metabolism, triggering bacterial ferroptosis-like death. Thus, the porous titanium scaffold, engineered with a piezoelectric nanoreactor, demonstrates superior antibacterial efficacy under ultrasound and facilitates osteogenesis via piezoelectric immunomodulation–activated therapy.
研究领域:
生物医学工程
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微生物学
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材料科学
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DOI
PubMed
高影响因子
RSC Chemical Biology
·
2023
·Vol. 4
·期 10
·774-784
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IF 4.1
Xiaojun He,Bingjie Han,Runming Wang,Yu Guo,Richard Y T Kao,Hongyan Li,Hongzhe Sun,Wei Xia
The opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa) causes infections that are difficult to treat, which is due to the bacterial natural resistance to antibiotics. The bacterium is also able to form a biofilm that protects the bacterium from clearance by the human immune system and leads to chronic infection. Herein, we synthesized and characterized a novel gallium compound that interferes with both the iron metabolism and quorum sensing system of P. aeruginosa to achieve a significant bactericidal activity. The compound could substantially reduce the secretion of bacterial virulence factors as well as eliminate biofilm formation. Integrative omics analysis indicates that this compound can significantly disturb the gene transcription and metabolism of P. aeruginosa. The effectiveness of the gallium compound was further validated in mammalian cell and murine skin infection models. Our study offers a new strategy to design new gallium-based antimicrobials to combat P. aeruginosa infection.
研究领域:
微生物学
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药理学
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感染病学
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PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Wenlong Xiao,Fang Wang,Xuchen Wang,Nani Wang
An imbalance in iron homeostasis contributes to mitochondrial dysfunction, which is closely linked to the pathogenesis of various diseases. Herein, we developed a nanosensor for detecting mitochondrial ferrous ions in vitro and in vivo . A poly( N -isopropylacrylamine)-coacrylic acid nanohydrogel was synthesized, and ferrous ions were detected using the fluorescent probe FeRhonox-1 embedded within it. (3-Carboxypropyl)-triphenylphosphonium bromide was chemically conjugated to the hydrogel matrix to enable mitochondrial targeting. The developed nanosensor showed a narrow particle size distribution, high sensitivity and selectivity for ferrous ions, and low cytotoxicity, enabling the nanosensor to sense and image ferrous ions in mitochondria with high spatial resolution. Changes in ferrous ion concentrations in human umbilical vein endothelial cells were measured and imaged after lipopolysaccharide (LPS) or iron dextran treatment. Moreover, the nanosensor was successfully used for ferrous ion imaging in live mice. The in vivo results showed that LPS injection induced the accumulation of mitochondrial ferrous ions. The proposed nanosensor could serve as a powerful tool for monitoring ferrous ions in mitochondria, providing strong support for studying disorders of iron metabolism.
研究领域:
生物化学
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医学影像
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分子生物学
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PubMed
高影响因子
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2023
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IF 3.5
Peng-Cheng Xu,Chang-Chun Song,Xiao-Ying Tan,Tao Zhao,Chong-Chao Zhong,Jie-Jie Xu,Yu-Feng Song,Zhi Luo
Background Iron is an essential metal element for organisms, whose metabolism is regulated by many genes and also dietary iron sources. However, the characterization, distribution and the responses of iron metabolism-related genes to different iron sources were not clear in fish. Methods The full-length cDNA sequences of fifteen iron metabolism-relevant genes ( tf , tfr1 , hp , fpn1 , ho1 , ho2 , tfr2 , hjv , hepcidin , fth , ftl , ftm , irp1 , irp2 and hif2α .) were obtained via 3′ and 5′ RACE PCR from yellow catfish, a widely distributed freshwater teleost in China and other Asian countries. Their molecular characterizations were analyzed via the bioinformatic methods. Real-time quantitative PCR was used to explore their mRNA distribution in nine tissues. Their mRNA expression responses in four tissues (heart, brain, kidney and gill) were explored in yellow catfish fed diets with five iron sources, including ferrous sulfate (FeSO 4 ), ferrous bisglycinate (Fe-Gly), ferrous chloride (FeCl 2 ), ferric citrate (Fe-CA) and ferric oxide nanoparticles (Fe 2 O 3 NPs). Results Compared with mammals and other teleost, these members shared similar domains. Their mRNAs were expressed in nine tested tissues, but mRNA levels varied. Yellow catfish fed the diets containing Fe-Gly and Fe 2 O 3 NPs had higher iron contents in heart, brain, kidney and gill. Meantime, different dietary iron sources addition affected their mRNA expression differentially in brain, heart, kidney and gill. It should be pointed out that only three biological replicate tanks were used in the present feeding treatment , and more biological replicate tanks (more than five) should be emphasized in further researches. Conclusion Taken together, our study identified fifteen iron metabolism-relevant genes, explored their mRNA expression in nine tissues, and their mRNA expression in the responses to different dietary iron sources in four tissues, indicating their important regulatory function in iron metabolism and homeostasis.
研究领域:
水产养殖
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分子生物学
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营养学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Jingjing Xie,Nansheng Wu,Dongming Li,Shiyi Xiong,Jinjiao Dong,Ruiling Wang,Guodong Zheng,Jingen Li
Iron deficiency anemia (IDA) is a prevalent nutritional deficiency problem. This study aimed to investigate the characteristics of Choerospondias axillaris polysaccharide-Fe (III) complex and its effect on IDA mice. CAP-Fe (III) complex was synthesized by co-thermal synthesis method with an iron content of 27.31 ± 0.97 %. The chelation of Fe 3+ reduced the crystallinity, increased the thermal stability and changed the morphological features of CAP, which was evidenced by XRD, TG, and SEM analysis. The probable existence of the β -FeOOH structure was supported by the characteristic absorption peaks in the FT-IR, XRD, and Mössbauer spectra. The CAP-Fe (III) complex showed a therapeutic effect on IDA mice, confirmed by improved erythroid parameters, iron levels, and oxidative stress. The results of gene expression levels determined by RT-qPCR demonstrated that the CAP-Fe (III) complex could regulate iron metabolism homeostasis, alleviate liver inflammation, and enhance intestinal barrier function. Furthermore, the dysbiosis of intestinal microbiota induced by IDA was effectively restored by CAP-Fe (III) complex, through enriching beneficial bacteria ( Firmicutes , Blautia , Oscillibacter , Colidextribacter ) and depleting harmful bacteria ( Actinobacteria , Proteobacteria , Parasutterella , Faecalibaculum , Escherichia-Shigella ). These findings suggested that CAP-Fe (III) may serve as a novel iron supplement for treating IDA.
研究领域:
营养学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Redox Biology
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2025
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IF 11.9
Chuanlin Feng,Lei Zhang,Xiaoyuan Zhou,Shiyu Lu,Ruowen Guo,Chao Song,Xin Zhang
The magnetic properties of substances directly determine their response to an externally applied magnetic field, which are closely associated with magnetoreception, magnetic resonance imaging (MRI), and magnetic bioeffects. However, people understanding of the magnetic properties of living organisms remains limited. In this study, we utilized NRF2 (nuclear factor erythroid 2-related factor 2) deficiency mice to investigate the contribution of redox (oxidation–reduction) homeostasis, in which the key process is the transfer of electron, a direct target of magnetic field and origin of paramagnetism. Our results show that the NRF2 -/- mice exhibit significantly altered systemic redox state, accompanied by increased magnetic susceptibility, particularly in the liver and spleen. Further analyses reveal that the levels of paramagnetic reactive oxygen species (ROS) in these tissues are markedly elevated compared to wild-type mice. Moreover, the concentrations of Fe 2+ and Fe 3+ are significantly elevated in NRF2 -/- mice, which are directly correlated with the increased magnetic susceptibility. The disrupted redox balance in NRF2 -/- mice not only exacerbates oxidative stress and iron deposition, but also induces impairs to the liver and spleen. The findings highlight the combined effects of ROS and iron metabolism in driving magnetic susceptibility changes, providing valuable theoretical insights for further research into magnetic bioeffects effects and organ-specific sensitivity to magnetic fields.
研究领域:
生物物理学
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分子生物学
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医学
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PubMed
高影响因子
ACS Pharmacology & Translational Science
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2025
·
IF 3.7
Qi-Xin Guan,Long-Bo Yu,Peng Wang,Qing-yuan Hu,Cai-Ping Tan
Triple-negative breast cancer (TNBC) is an aggressive malignancy, with limited targeted treatment options. In this study, we developed a novel triphenylphosphine (TPP)-modified deferasirox (DFX) titanium complex (Ti-DFX-TPP) to disrupt iron homeostasis in TNBC cells through transmetalation. Ti-DFX-TPP depletes the labile iron pool, triggering a compensatory upregulation of transferrin receptor 1 (TfR1) in response to an intracellular iron deficiency. The disruption of iron metabolism by Ti-DFX-TPP increases reactive oxygen species (ROS) levels, which in turn lead to mitochondrial dysfunction and DNA damage, ultimately inhibiting cancer cell growth. In vivo studies further demonstrated that Ti-DFX-TPP inhibits tumor growth without significant toxicity to major organs. These findings suggest that Ti-DFX-TPP is a promising therapeutic candidate for TNBC, as it exploits the disruption of iron metabolism and ROS pathways to enhance its anticancer efficacy.
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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DOI
PubMed
高影响因子
Autophagy
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2025
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IF 14.3
Chenyu Luo,Haisheng Liang,Mintao Ji,Caiyong Ye,Yiping Lin,Yuhan Guo,Zhisen Zhang,Yinyin Shu,Xiaoni Jin,Shuangshuang Lu,Wanling Lu,Yazheng Dang,Hong Zhang,Bingyan Li,Guangming Zhou,Zengli Zhang,Lei Chang
Ferroptosis is an iron-dependent regulated form of cell death implicated in various diseases, including cancers, with its progression influenced by iron-dependent peroxidation of phospholipids and dysregulation of the redox system. Whereas the extracellular matrix of tumors provides mechanical cues influencing tumor initiation and progression, its impact on ferroptosis and its mechanisms remains largely unexplored. In this study, we reveal that heightened mechanical tension sensitizes cells to ferroptosis, whereas decreased mechanics confers resistance. Mechanistically, reduced mechanical tension reduces intracellular free iron levels by enhancing FTH1 protein expression. Additionally, low mechanics significantly diminishes NCOA4, pivotal in mediating FTH1 phase separation-induced ferritinophagy. Targeting NCOA4 effectively rescues ferroptosis susceptibility under low mechanical tension through modulation of FTH1 phase separation-driven autophagy. In conclusion, our findings demonstrate that mechanics regulates iron metabolism via NCOA4-FTH1 phase separation-mediated autophagy, thereby influencing ferroptosis sensitivity and offering promising therapeutic avenues for future exploration.
研究领域:
癌症生物学
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细胞代谢
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力学生物学
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分子生物学
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PubMed
高影响因子
Frontiers in Immunology
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2023
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IF 7.3
Liu Xun,Hu Ya-Zhen,Pan Yi-Ru,Liu Jia,Jiang You-Bo,Zhang Yong-An,Zhang Xu-Jie
Antimicrobial peptides are important components of the host innate immune system, forming the first line of defense against infectious microorganisms. Among them, liver-expressed antimicrobial peptides (LEAPs) are a family of antimicrobial peptides that widely exist in vertebrates. LEAPs include two types, named LEAP-1 and LEAP-2, and many teleost fish have two or more LEAP-2s. In this study, LEAP-2C from rainbow trout and grass carp were discovered, both of which are composed of 3 exons and 2 introns. The antibacterial functions of the multiple LEAPs were systematically compared in rainbow trout and grass carp. The gene expression pattern revealed that rainbow trout and grass carp LEAP-1, LEAP-2A, LEAP-2B and/or LEAP-2C were differentially expressed in various tissues/organs, mainly in liver. After bacterial infection, the expression levels of LEAP-1, LEAP-2A, LEAP-2B and/or LEAP-2C in the liver and gut of rainbow trout and grass carp increased to varying degrees. Moreover, the antibacterial assay and bacterial membrane permeability assay showed that rainbow trout and grass carp LEAP-1, LEAP-2A, LEAP-2B and LEAP-2C all have antibacterial activities against a variety of Gram-positive and Gram-negative bacteria with varying levels through membrane rupture. Furthermore, cell transfection assay showed that only rainbow trout LEAP-1, but not LEAP-2, can lead to the internalization of ferroportin, the only iron exporter on cell surface, indicating that only LEAP-1 possess iron metabolism regulation activity in teleost fish. Taken together, this study systematically compared the antibacterial function of LEAPs in teleost fish and the results suggest that multiple LEAPs can enhance the immunity of teleost fish through different expression patterns and different antibacterial activities to various bacteria.
研究领域:
免疫学
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分子生物学
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微生物学
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鱼类生理学
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DOI
PubMed
高影响因子
BIOMETALS
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2019
·Vol. 32
·期 2
·251-264
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IF 2.455
Liu Xiao-Li,Ye Sen,Li Hua-Wei,Lu Bo,Yu Yan-Qin,Fan Yu-Peng,Yang Wei-Jun,Yang Jin-Shu
Rimicaris exoculata (Decapoda: Bresiliidae) is one of the dominant species among hydrothermal vent communities along the Mid-Atlantic Ridge. This shrimp can tolerate high concentrations of heavy metals such as iron, but the mechanisms used for detoxification and utilization of excess metals remain largely unknown. Ferritin is a major iron storage protein in most living organisms. The central heavy subunit of ferritin (H-ferritin) possesses ferroxidase activity and converts iron from Fe 2+ to Fe 3+ , the non-toxic form used for storage. In the present study, the H-ferritin RexFrtH was identified in the hydrothermal vent shrimp R. exoculata , and found to be highly expressed in the gill, the main organ involved in bioaccumulation of metals, at both RNA and protein levels. Accumulation of RexFrtH decreased from efferent to afferent vessels, coinciding with the direction of water flow through the gills. Fe 3+ was localized with RexFrtH, and in vitro iron-binding and ferroxidase assays using recombinant RexFrtH confirmed the high affinity for iron. Based on these results, we propose a model of iron metabolism in R. exoculata gills; ferrous iron from ambient hydrothermal water accumulates and is converted and stored in ferric form by RexFrtH as an iron reservoir when needed for metabolism, or excreted as an intermediate to prevent iron overload. The findings expand our understanding of the adaptation strategies used by shrimps inhabiting extreme hydrothermal vents to cope with extremely high heavy metal concentrations.
研究领域:
海洋生物学
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分子生物学
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生物化学
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PubMed
高影响因子
ACS Nano
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2018
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IF 13.709
Tao Liu,Wenlong Liu,Mingkang Zhang,Wuyang Yu,Fan Gao,Chuxin Li,Shi-Bo Wang,Jun Feng,Xian-Zheng Zhang
Non-apoptotic ferroptosis is of clinical importance because it offers a solution to the inevitable biocarriers of traditional apoptotic therapeutic means. Inspired by industrial electro-Fenton technology featured with electrochemical iron cycling, we construct ferrous-supply-regeneration nanoengineering to intervene tumorous iron metabolism for enhanced ferroptosis. Fe3+ ion and naturally derived tannic acid (TA) spontaneously form a network-like corona onto sorafenib (SRF) nanocores. The formed SRF@FeIIITA nanoparticles can respond to a lysosomal acid environment with corona dissociation, permitting SRF release to inhibit GPX4 enzyme for ferroptosis initiation. TA is arranged to chemically reduce the liberated and the ferroptosis-generated Fe3+ to Fe2+, offering iron redox cycling to, thus, effectively produce lipid peroxide required in ferroptosis. Sustained Fe2+ supply leads to long-term cytotoxicity, which is identified to be specific to H2O2-overloaded cancer cells but minimal in normal cells. SRF@FeIIITA-mediated cell death proves to follow the ferroptosis pathway and strongly inhibits tumor proliferation. Moreover, SRF@FeIIITA provides a powerful platform capable of versatile integration between apoptosis and non-apoptosis means. Typically, photosensitizer-adsorbed SRF@FeIIITA demonstrates rapid tumor imaging owing to the acid-responsive fluorescence recovery. Together with ferroptosis, imaging-guided photodynamic therapy induces complete tumor elimination. This study offers ideas about how to advance anticancer ferroptosis through rational material design.
研究领域:
纳米医学
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肿瘤学
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诊疗学
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材料科学
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DOI
PubMed
高影响因子
Human Cell
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2025
·Vol. 39
·期 1
·27
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IF 3.1
Xu Jianfeng,Lei Deng,Xu Peng,Wang Yuqi,Li Zhupeng,Wu Jiacheng,Feng Weizhong,Zhou Junqing
Esophageal cancer (EC) remains a highly aggressive malignancy with limited therapeutic success, partly due to heterogeneous responses to neoadjuvant chemotherapy (NAC). Tumor-derived exosomes and tumor-associated macrophages play critical roles in shaping the immunosuppressive tumor microenvironment, but their crosstalk in EC chemoresistance remains unclear. In this study, we identified tumor-derived exosomal miR-145-5p as a potential predictor of poor NAC response. Elevated exosomal miR-145-5p levels were associated with increased M2 macrophage infiltration and enhanced expression of M2 markers in EC tissues. Mechanistically, miR-145-5p promoted M2 macrophage polarization through the suppression of transferrin receptor (TFRC) and subsequent disruption of iron uptake. Consequently, these tumor-promoting M2-polarized macrophages enhanced EC cell proliferation, migration, invasion, and cisplatin resistance. In vivo, macrophages overexpressing miR-145-5p facilitated tumor growth and markedly weakened the therapeutic effects of cisplatin. Overall, our findings reveal that EC cells utilize exosomal miR-145-5p to remodel macrophages into a pro-tumorigenic phenotype through TFRC-dependent iron metabolic reprogramming, contributing to malignant progression and chemoresistance. Exosomal miR-145-5p may represent a promising biomarker for NAC response and a therapeutic target to improve treatment outcomes in EC.
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高影响因子
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