ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Wendi Han,Chenfang Miao,Xintian Zhang,Yinning Lin,Xiaoli Hao,Zhengjun Huang,Shaohuang Weng,Xinhua Lin,Xianzhong Guo,Jianyong Huang
The content of deferasirox (DEF) in plasma is significant in β-thalassemia patient that needs long-term transfusion therapy, while the effective and simple strategy for DEF monitoring is still limited. The carbon dots (CDs) prepared from citric acid monohydrate and glutathione exhibit weakly modulated fluorescence intensity to several common metal ions containing Cu 2+ . Interestingly, the process of interaction of Cu 2+ and DEF forms the chelation of Cu 2+ and DEF (Cu-DEF) with the absorbance wavelength of DEF at 320 nm shifting to 332 nm for Cu-DEF. And the obtained Cu-DEF will effectively quench CDs through inner filter effect (IFE). Accordingly, a facile signal-off fluorescent method based on CDs as probe is developed for DEF detection using Cu 2+ as medium. And the proposed method exhibits linear range of 0.5–20 μg/mL with the detection limit of 0.33 μg/mL for DEF under the optimized conditions. Moreover, the developed assay is further expanded to test the content of DEF in dispersible tablet and plasma with accuracy and reproducibility. Such cost-effective and sensitive fluorescent assay just through simple mixing operation present a valuable strategy for drug monitoring.
研究领域:
医学
·
分析化学
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DOI
PubMed
高影响因子
XENOBIOTICA
·
2021
·
IF 1.908
Xiaojiao Zheng,Xu Wang,Zifang Ding,Wei Li,Ying Peng,Jiang Zheng
Deferiprone (DFP) is a metal chelating agent generally used to treat patients with thalassaemia, due to iron overload in clinical settings.Studies have revealed that long-term use of DFP can induce hepatotoxicity, however, mechanisms of its toxic action remain unclear. The present studies are aimed to characterize the reactive metabolite of DFP, to define the metabolic pathway, and to determine the P450 enzymes participating in the bioactivation.A demethylation metabolite (M1) was observed in rat liver microsomal incubations. Additionally, a glutathione (GSH) conjugate (M2) and an N-acetylcysteine (NAC) conjugate (M3) were detected in microsomal incubations fortified with DFP and GSH/NAC.Biliary M2 and urinary M3 were respectively found in animals administered DFP.CYP2A6 enzyme dominated the catalysis to bioactivate DFP.
研究领域:
药理学
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毒理学
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临床医学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2015
·
IF 1.602
Xiaoming Zhang,Yuyang Tian,Jiangtao Jia,Tingting Zhang,Guangshan Zhu
In this paper we present three new cocrystals based on deferiprone which is the first oral medicine as iron chelator . Solitary deferiprone possesses some known problems due to its good solubility and frequent dosing side effects. For these three novel co crystals, deferiprone is the active pharmaceutical ingredient (API), p -hydroxybenzoic acid (1, C 7 H 9 NO 2 ·C 7 H 6 O 3 ), 2, 5-dihydroxybenzoic acid (2, C 7 H 9 NO 2 ·C 7 H 6 O 4 ) and maleic acid (3, C 7 H 9 NO 2 ·C 4 H 4 O 4 ) are used as cocrystal formers (CCFs), respectively. Their structures were characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD) analysis, thermogravimetric analyses (TGA), differential thermal analysis (DTA), elemental analysis (EA) and infrared spectral analysis (IR). Single crystal X-ray diffraction demonstrates that all three cocrystals (1–3) possess strong hydrogen-bondings assembled through hydroxyl of API and carboxylic acids of CCFs. The PXRD results indicate their high purity of as-synthesized samples. TGA, DTA, EA, IR and dissolution study of API and cocrystals were also measured and discussed, respectively. The results suggest that the cocrystals exhibit low dissolution rates comparing with solitary deferiprone, which is very advantageous for the oral medicine with frequent dosing side effects.
研究领域:
药学
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材料科学
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DOI
高影响因子
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
·
2019
·Vol. 24
·期 3
·331-341
·
IF 3.632
Timoshnikov V. A.,Kobzeva T.,Selyutina O. Y.,Polyakov N. E.,Kontoghiorghes G. J.
Copper ions can catalyze the production of free oxygen radicals (•OH and •OOH) similar to iron ions. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced toxicity in copper-related diseases where there is an increase in copper levels and also when Cu homeostasis and regulation are disrupted. An antioxidant/chelator inhibiting Cu-induced oxidative damage could play a significant role in the treatment of such Cu-related diseases. Deferiprone has high affinity for copper binding and can be considered for the potential treatment of copper toxicity and overloading conditions, such as Wilson’s disease. In the present study, the ability of deferiprone to inhibit the production of hydroxyl radicals catalyzed by copper ions was elucidated using an Electron Paramagnetic Resonance (EPR) spin trapping technique. The values of g-factors and hyperfine splitting constants were calculated for Cu(II)-deferiprone 1:1 complex: ( a = 58.5 G, g = 2.1667) and 1:2 complex: ( a = 73.0 G, g = 2.1378). The TMIO spin trap (2,2,4-trimethyl-2 H -imidazole-1-oxide) was used for the detection of free radicals formed in Fenton-like copper-catalyzed reactions. It was demonstrated that the interaction of deferiprone with Cu 2+ ions completely inhibited hydroxyl radical (•OH) production in the presence of hydrogen peroxide. It was found also that deferiprone inhibits Cu-induced oxidation of linoleic acid in micellar solution. In addition to existing data for water solutions, the affinity of deferiprone for copper binding in non-aqueous environment has been elucidated.
研究领域:
生物化学
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医学
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DOI
PubMed
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 55
·34525-34532
·
IF 3.361
Chen-Fang Miao,Xian-Zhong Guo,Xin-Tian Zhang,Yin-Ning Lin,Wen-Di Han,Zheng-Jun Huang,Shao-Huang Weng
The monitoring of deferasirox (DEF) has important clinical roles in patients who need iron excretion. However, analytical methods with practicability and simplicity are limited. Moreover, ratiometric fluorescence strategies based on Förster resonance energy transfer (FRET) from carbon dots (CDs) as a donor are rarely reported as a drug monitor. In this work, CDs with an appropriate emitting wavelength at 480 nm and excitation around 370 nm were prepared by hydrothermal approach and HCl post-treatment. O-Phenylenediamine (OPD) can be oxidized by Cu2+ to produce yellow fluorescent 2,3-diaminophenazine (oxOPD) in the system of Cu2+ and OPD (Cu–OPD). Correspondingly, a remarkable FRET from CDs to oxOPD in the system of CDs, Cu2+ and OPD (CDs–Cu–OPD) was fabricated with the quenching illustration of CDs, but emitting property of oxOPD. Attributed to the chelation ability of DEF on Cu2+, the inhibitory effects of DEF on the Cu2+-triggered oxidative capability reduced the FRET system by the decreased oxOPD. Thus, the recovered CDs at F480 and decreased oxOPD at F560 were found through a ratiometric mode by the addition of DEF in CDs–Cu–OPD for the DEF assay. The FRET behavior of CDs and oxOPD in CDs–Cu–OPD was proved clearly through the calculation of the association constant, binding constant, number of binding sites, and the distance between the donor and acceptor. Furthermore, this ratiometric method exhibited promising analytical performance for DEF with the application in real samples. The implementation of this work expands the application field of CDs and OPD oxidation in drug monitoring, and even other biological analyses through ratiometric strategy.
研究领域:
分析化学
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药物分析
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生物医学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2025
·
IF 7.9
Ruping Li,Yanxin Wu,Lvchen He,Ruotong Yang,Kaipei Luo,Fei Gao,Haipo Yuan,Yu Zheng,Yao He
The wound of diabetes is closely related to inflammation, reactive oxygen species production, impaired angiogenesis and bacterial infection. It is urgent to develop a hydrogel dressing with antibacterial and anti-inflammatory properties and promoting angiogenesis to achieve efficient wound healing. Carboxymethyl chitosan (CMCS) is obtained by chemical modification of chitosan, which has excellent biocompatibility and rapid gel properties. Deferiptyline (DFO) has the ability to increase the expression of HIF-1α, which promotes the release of endogenous growth factors related to angiogenesis. Luteolin (LUT), the active ingredient of traditional Chinese medicine, shows unique advantages in treating diabetes wounds. In this study, polysaccharide hydrogel prepared by combining DFO and LUT has excellent antibacterial and antioxidant properties, promotes cell migration, releases LUT and DFO at the wound site, and enhances angiogenesis through HIF-1α and VEGFA pathways. The hydrogel synergistically promotes cell migration, angiogenesis and effectively eliminates drug-resistant bacteria, which is beneficial to wound healing of diabetes. This study has created a multifunctional hydrogel loaded with DFO and crosslinked polysaccharide, an active ingredient of traditional Chinese medicine, with sustained release, enhanced permeability and great biocompatibility, which can be used as an excellent antibacterial dressing for diabetes wounds.
研究领域:
生物材料学
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医学
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药理学
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DOI
高影响因子
WATER RESEARCH
·
2024
·
IF 11.4
Juanlong Li,Yezi Hu,Zewen Shen,Huihui Jin,Rong He,Wenkun Zhu,Guixia Zhao,Zhuoyu Ji,Bin Ma,Xiangke Wang
ABSTRACT Extracting uranium (U(VI)) from fluoride-rich radioactive wastewater is of great significance for the development of nuclear energy and environmental remediation. The presence of thermodynamically stable [UO 2 F n ] 2−n (n= 0, 1, 2, 3, 4) aqueous complexes in fluoride-rich U(VI)-containing wastewater significantly hinders the efficiency of uranyl extraction and recovery using conventional methods. In this study, we report a direct precipitation method using deferiprone ligands for efficient uranyl extraction from fluoride-rich wastewater that offsets the preparation of solid materials. The deferiprone ligands exhibited exceptional chelating ability competing toward F − . In simulated 2.1 × 10 -4 mol/L U(VI) wastewater with F − concentrations ranging from 1 to 10 g/L, adjusting the amount of deferiprone ligands enabled a high U(Ⅵ) precipitation rate of 97.60% to 86.90%, correspondingly. A remarkable 99.71% recovery of U(Ⅵ) from real fluoride-rich alkaline wastewater was achieved within 2 hours. Detailed investigations revealed that the competitive chelating by deferiprone ligands results in the formation of insoluble U(VI)-deferiprone complexes ([(UO 2 )(H 2 O)(C 7 NO 2 H 8 ) 2 ]·4H 2 O), driven by π-π stacking interactions, electrostatic attractions, and intermolecular hydrogen bonds. Given the cost-efficiency and excellent radiation resistance of deferiprone ligands, this efficient and straightforward precipitation approach holds great promise for practical applications in U(VI) remediation and resource recovery from fluoride-rich wastewater.
研究领域:
环境科学
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核化学
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废水处理
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材料科学
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DOI
PubMed
高影响因子
Neural Regeneration Research
·
2024
·Vol. 19
·期 12
·2708
·
IF 5.9
Fang He,Li Mengjie,Yang Jingchen,Ma Shunping,Zhang Li,Yang Hongqi,Tang Qiongyan,Cao Jing,Yang Weimin
Thalamic hemorrhage can lead to the development of central post-stroke pain. Changes in histone acetylation levels, which are regulated by histone deacetylases, affect the excitability of neurons surrounding the hemorrhagic area. However, the regulatory mechanism of histone deacetylases in central post-stroke pain remains unclear. Here, we show that iron overload leads to an increase in histone deacetylase 2 expression in damaged ventral posterolateral nucleus neurons. Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium (Kv) channel subunit gene in a rat model of central post-stroke pain, thereby increasing Kcna2 expression and relieving central pain. However, in the absence of nerve injury, increasing histone deacetylase 2 expression decreased Kcna2 expression, decreased Kv current, increased the excitability of neurons in the ventral posterolateral nucleus area, and led to neuropathic pain symptoms. Moreover, treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage, reversed histone deacetylase 2 upregulation and Kv1.2 downregulation, and alleviated mechanical hypersensitivity in central post-stroke pain rats. These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation, mediated by iron overload, are important factors in central post-stroke pain pathogenesis and could serve as new targets for central post-stroke pain treatment.
研究领域:
神经科学
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药理学
·
分子生物学
·
神经病学
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DOI
PubMed
高影响因子
MEDICAL MICROBIOLOGY AND IMMUNOLOGY
·
2025
·Vol. 214
·期 1
·1-13
·
IF 3
Ding Zhi-Wen,Xu Kai-Zhong,Dar Owias Iqbal,Yin Lu-Jun,Wang Ying-Jie,Liao Yun-tong,Wang Peng,Jia Ai-Qun
Burkholderia cenocepacia , an opportunistic pathogen, poses a significant threat to human health, necessitating the discovery of effective quorum sensing inhibitors (QSIs). In this study, the quorum sensing inhibitory effects of deferiprone (DFP) on the B. cenocepacia 162,638 were validated. Notably, DFP demonstrated an ability to inhibit and disrupt bacterial biofilms, reducing biofilm formation by 44.59% at 1/4 MIC (minimum inhibitory concentration) and 24.32% at 1/8 MIC concentrations. The study also investigated DFP’s impact on motility, virulence, and QS signal levels. LC-MS/MS analysis showed a gradual reduction in the QS molecule C6-HSL as DFP concentrations increased. Additionally, DFP’s non-hemolytic properties and safety profile, as verified in Galleria mellonella infection models, highlighted its biocompatibility. RT-qPCR results further indicated that DFP downregulated QS-related gene expression, particularly those involved in ferric uptake regulation protein (Fur). Molecular docking studies identified Fur as a key target for DFP’s inhibitory action. Collectively, DFP was shown as a potential QSI with practical applications for controlling B. cenocepacia infections.
研究领域:
微生物学
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传染病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Yang Li,Chen Yang,Shilin Wang,Dong Yang,Yu Zhang,Li Xu,Liang Ma,Jiaojiao Zheng,Robert B. Petersen,Ling Zheng,Hong Chen,Kun Huang
Protein fibrils drive the onset and progression of many diseases in a prion-like manner, i.e. they transcellular propagate through the extracellular space to health cells to initiate toxic aggregation as seeds. The conversion of native α-synuclein into filamentous aggregates in Lewy bodies is a hallmark of Parkinson's disease (PD). Copper and iron ions accumulate in PD brains, however, whether they influence the prion-like propagation of α-synuclein remain unclear. Here, we reported that copper/iron ions accelerate prion-like propagation of α-synuclein fibrils by promoting cellular internalization of α-synuclein fibrils, intracellular α-synuclein aggregation and the subsequent release of mature fibrils to the extracellular space to induce further propagation. Mechanistically, copper/iron ions enhanced α-synuclein fibrils internalization was mediated by negatively charged membrane heparan sulfate proteoglycans (HSPGs). α-Synuclein fibrils formed in the presence of copper/iron ions were more cytotoxic, causing increased ROS production, cell apoptosis, and shortened the lifespan of a C. elegans PD model overexpressing human α-synuclein. Notably, these deleterious effects were ameliorated by two clinically used chelators, triethylenetetramine and deferiprone. Together, our results suggest a new role for heavy metal ions, e.g. copper and iron, in the pathogenesis of PD through accelerating prion-like propagation of α-synuclein fibrils.
研究领域:
神经科学
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分子生物学
·
病理学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Kaiyuan Chen,Yahui Tang,Linhua Lan,Mengxuan Li,Zhongqiu Lu
Acute kidney injury (AKI) induced by diquat (DQ) progresses rapidly, leading to high mortality, and there is no specific antidote for this chemical. Our limited knowledge of the pathogenic toxicological mechanisms of DQ has hindered the development of treatments against DQ poisoning. Pyroptosis is a form of programmed cell death and was recently identified as a novel molecular mechanism of drug-induced AKI. To explore the role of pyroptosis in HK-2 cells exposed to DQ, the plasma membrane damage of the cells was detected by LDH release assay. Western blot was performed to detect the cleavage of GSDME. Proteomics analysis was performed to explore the mechanism of DQ induced nephrotoxicity . FerroOrange probe was used to measure the intracellular Fe 2+ levels. Herein, we show that DQ induces pyroptosis in HK-2 cells. Mechanistically, DQ induces the accumulation of mitochondrial ROS and initiates the cleavage of gasdermin E (GSDME) in an intrinsic mitochondrial pathway. Knockout of GSDME attenuated DQ-induced cell death. Further analysis revealed that loss of FTH1 induces Fe 2+ accumulation, contributing to DQ-induced pyroptosis. Knockdown LC3B could help restore the expression of FTH1 and improve cell viability . Moreover, we found DFO , an iron chelator , could reduce cellular Fe 2+ levels and inhibit pyroptosis. Collectively, these findings suggest an unrecognized mechanism for GSDME-dependent pyroptosis in DQ-induced AKI.
研究领域:
毒理学
·
细胞生物学
·
肾脏病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Yaru Li,Qian Yang,Lanlan Fan,Fang Liu,Yaqi Shang,Baoxin Zhang,Zheng Wang,Yanjun Zhao
Ovarian cancers (OC) often resist current standard chemotherapy because of the cancer heterogeneity and over-expression of an anti-apoptotic protein, myeloid cell leukemia-1 (MCL-1). The heterogeneous OC shows impaired redox homeostasis and relies heavily on glutathione peroxidase 4 to eliminate toxic lipid peroxides. Therefore, integrated apoptosis and ferroptosis therapy is promising for OC management. The current work reports a liposomal nanosystem for apoptotic and ferroptotic OC therapy. Simvastatin (Sim) and vorinostat (Saha) were selected as the pleiotropic model drugs. The successive release of Saha and Sim from liposomes enabled the sequential amplification of MCL-1 by Saha, and then MCL-1 inhibition by Sim. Such a strategy could potently induce apoptosis in a human OC cell line (SKOV3), as indicated by increased intracellular cytochrome c concentration, caspase 3/9 activity, and the extent of apoptosis. Besides, Saha played multiple roles in cell death. It could induce cell cycle arrest at the G 2 /M phase and apoptosis. Saha also inhibited the glutamate-cystine transporter (SLC7A11) and provoked ferroptosis, which was corroborated by the depletion of glutathione, reduced nicotinamide adenine dinucleotide phosphate, and boost of lipid peroxides and malondialdehyde in SKOV3 cells. The current work integrated the “sequential amplification and inhibition of MCL-1 target” concept with combinational apoptosis and ferroptosis OC therapy, which might offer a new approach for managing resistant OC and other malignant diseases.
研究领域:
肿瘤学
·
药学
·
细胞生物学
·
纳米技术
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产品关联
DOI
高影响因子
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