FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Tao Bai,Luhao Wang,Zhentao Qiao,Zhiwei Wang
Diabetic patients are considered as the high risk population to develop critical limb ischemia (CLI), a peripheral vascular disease (PVD) resulted from atherosclerosis. Cuproptosis is a novel copper-dependent cell death that has shown the regulatory role in diabetes, while its effect on diabetic CLI has not been explored yet. In this study, Diabetic CLI mice was induced by femoral artery ligation (FAL) on diabetic mice. Endothelial injury in diabetic CLI was mimicked in human microvascular endothelial cells (HMEC-1) via the induction with high glucose (HG) and nutrient deprivation (ND). Besides, copper chelator Ammonium Tetrathiomolybdate (TM), which has shown the anti-cuproptosis property, was administrated to explore its potential effects on diabetic CLI mice and HG/ND-induced HMEC-1 cells. Strikingly, obvious cuproptosis was found in the gastrocnemius muscles of diabetic CLI mice and HG/ND-induced HMEC-1 cells, as evidenced by the copper overload and dysregulated cuproptosis-related proteins (such as Fe-S cluster proteins, copper exporter ATP7A, and copper importer SLC31A1). More importantly, TM protected against the hindlimb ischemic damages in diabetic CLI mice and alleviated cuproptosis-associated cell deaths in HG/ND-induced HMEC-1 cells. In summary, this study indicates the involvements of cuproptosis in diabetic CLI, and provides novel insights into copper chelator TM on diabetic CLI therapy.
研究领域:
医学
·
分子生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Junya Lu,Shuaipeng Feng,Zhu Liu,Yan Xiao,Hui Zhang,Siling Wang,Qinfu Zhao
The notably heightened copper levels found in cancer underscore the critical involvement of copper ions in tumor progression and metastasis. Consequently, disrupting tumor copper homeostasis is emerging as a novel strategy for cancer treatment. Here, LTMP was constructed using PEG-modified mesoporous polydopamine (MP) loaded with lonidamine (LND, a glycolysis inhibitor) and tetrathiomolybdate (TM, a copper chelator). The utilization of TM as a copper chelator led to a substantial reduction in copper content and inhibited the activity of copper-dependent enzymes, thereby suppressing the oxidative phosphorylation (OXPHOS) process in tumor cells. However, the inhibition of OXPHOS lead to compensatory upregulation of glycolysis, enhancing cellular drug resistance. Therefore, the combination of LND and TM could effectively achieve dual inhibition of glycolysis and OXPHOS, resulting in a substantial enhancement of tumor cell apoptosis. Furthermore, LTMP was found to inhibit the activities of matrix metalloproteinases and lysyl oxidase, thereby impeding the epithelial-mesenchymal transition process and significantly reducing lung tumor metastasis. Additionally, LTMP-based photothermal therapy combined with chemotherapy effectively regulated the tumor microenvironment by reducing immunosuppressive cells and enhancing T lymphocyte infiltration. This work provided new insights for the design of intricate anti-tumor strategies.
研究领域:
肿瘤学
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生物无机化学
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药物递送系统
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代谢调控
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转化医学
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DOI
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Zishan Zeng,Jingwen Jiang,Yue Sun,Wanzhen Li,Dong Zheng,Huanxin Lin,Chunshun Zhao
Helicobacter pylori ( H. pylori ) is considered as the major pathogenic factor related to multiple digestive diseases. However, the efficacy of first-line treatment containing antibiotics gradually declined. It is urgent to develop treatment with antibiotic reduction/abandonment to combat H. pylori . Based on our previous discovery that Cu(DTC) 2 exhibited stronger bactericidal effect than that of disulfiram or diethyldithiocarbamate (DTC), we constructed an antibiotic-free therapeutic strategy composed of DTC prodrug, Cu 2+ and shikonin (SK) to eliminate H. pylori . DTC was firstly modified with nitroaromatic moiety to acquire DTC prodrug (NTR-DTC), which was further encapsulated into Cu-SK@DOPA to construct nanoprodrug Cu-SK@NTR-DTC to achieve the triple masking of DTC, Cu 2+ and SK for the specificity therapeutics. Cu-SK@NTR-DTC could penetrate mucus layer and mainly detain in the bacteria infection area. In the presence of H. pylori , DTC was released from NTR-DTC to recover activity of copper chelation, and competitively bound Cu 2+ from Cu-SK to form Cu(DTC) 2 . The released SK possessed the bactericidal sensitization effect on Cu(DTC) 2 . The H. pylori -activable dissociation of Cu-SK@NTR-DTC, and the local release of Cu(DTC) 2 and SK seriously destructed the bacterial membranes integrity and induce H. pylori death, which provided a feasible strategy to address the clinical limitations of H. pylori clearance.
研究领域:
医学
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药学
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DOI
PubMed
高影响因子
MACROMOLECULAR RAPID COMMUNICATIONS
·
2016
·Vol. 37
·期 15
·1275-1281
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IF 4.638
Jie Han,Kaiyi Zhou,Xuechao Zhu,Qiuping Yu,Yi Ding,Xinhua Lu,Yuanli Cai
Understanding nanoscale structural hierarchy/complexity of hydrophilic flexible polymers is imperative because it can be viewed as an analogue to protein-alike superstructures. However, current understanding is still in infancy. Herein the first demonstration of nanoscale structural hierarchy/complexity via copper chelation–induced self-assembly (CCISA) is presented. Hierarchically-ordered colloidal networks and disks can be achieved by deliberate control of spacer length and solution pH. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy demonstrate that CCISA underwent supramolecular-to-supracolloidal stepwise-growth mechanism, and underline amazing prospects to the hierarchically-ordered superstructures of hydrophilic flexible polymers in water.
研究领域:
材料科学
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生物物理学
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纳米技术
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2012
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IF 4.555
Tao Li,Haoyue Xie,Zhifeng Fu
A facile, sensitive and universal method was established for analysis of biogenic amines using micellar electrokinetic chromatography coupled with chemiluminescent (CL) detection. It was found that diperiodatocuprate (III) (K 5 [Cu(HIO 6 ) 2 ], DPC), a transition metal chelate at unstable high oxidation state, could effectively enhance the reaction between luminol-type compound and hydrogen peroxide, to produce very strong CL signal. In addition, triethylamine was found to be able to effectively improve the yield of the derivatization reaction between biogenic amines and a luminol-type derivatization reagent, N -(4-aminobutyl)- N -ethylisoluminol (ABEI). Based on these facts, three biogenic amines were pre-column derivatized with ABEI, and post-column detected using high sensitive luminol-hydrogen peroxide-DPC CL system. Since the background was quite low, and the signal was quite strong, a considerable improved sensitivity was obtained. The presented method had been successfully applied to simultaneously analyze glycine, proline and phenylalanine with the detection limits (S/N = 3) of 0.030 μmol L −1 , 0.23 μmol L −1 and 0.21 μmol L −1 , respectively. To evaluate its potential application value, glycine in saliva and urine samples was detected using this method, and satisfied results were obtained. This approach can be further extended to detection of many other compounds such as peptides and drugs by using luminol-type derivatization reagent.
研究领域:
分析化学
·
生物化学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Xing Ge,Shuyue Deng,Lilin Chen,Feng Feng,Tianye Fang,Yu Ding,Hui Jiang,Jun Yang,Xinmei Liu,Jianjun Dai,Lei Yang,Yanmin Ju
Fungal infections pose a significant global public health threat, particularly candidemia and biofilm formation. Current antifungal drugs have limitations due to their toxicity and drug resistance. Ion interference therapy, particularly cuproptosis, shows significant potential for disease treatment. Herein, nano copper-chelate Cu(DDC) 2 @BSA (CDB) is synthesized for antifungal research and the mechanism of cuproptosis-like death is investigated. Initially, CDB demonstrates a strong inhibitory effect on multiple fungi and exhibits strong antifungal activity against two fluconazole-resistant clinical isolates. The decrease in ATPase activity and mitochondrial membrane potential indicates that the antifungal mechanism may involve mitochondrial dysfunction. Subsequently, transcriptome analysis reveals significant alterations in genes related to copper ions transport and regulation, oxidative phosphorylation, and mitochondrial function. Additionally, copper ions overload is observed, along with an increase in heat shock protein 70 levels and a decrease in lipoic acid synthetase protein expression. Given that biofilms hinder drug penetration, quaternary ammonium chitosan microneedles are employed in combination with CDB to penetrate the biofilm barrier and enhance the antifungal effect. Overall, this study provides new insight into the cuproptosis-like death mechanism in fungi and presents a promising strategy for fungal infection treatment through the combination of nano copper–chelate and microneedle delivery system.
研究领域:
微生物学
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药理学
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分子生物学
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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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