Batteries-Basel
·
2025
·Vol. 11
·期 8
·289
·
IF 4.8
Shan-Diao Xu,Li-Cheng Wu,Muhammad Adil,Lin-Feng Sheng,Zi-Yue Zhao,Kui Xu,Xin Chen
To develop high-performance electrode materials for supercapacitors, in this paper, a heterostructured composite material of cerium sulfide and zinc sulfide quantum dots (CeS2/ZnS QD) was successfully prepared by hydrothermal method. Characterization through scanning electron microscopy (SEM), X-ray diffraction (XRD), and transmission electron microscopy (TEM) showed that ZnS QD nanoparticles were uniformly composited with CeS2, effectively increasing the active sites surface area and shortening the ion diffusion path. Electrochemical tests show that the specific capacitance of this composite material reaches 2054 F/g at a current density of 1 A/g (specific capacity of about 256 mAh/g), significantly outperforming the specific capacitance of pure CeS2787 F/g at 1 A/g (specific capacity 98 mAh/g). The asymmetric supercapacitor (ASC) assembled with CeS2/ZnS QD and activated carbon (AC) retained 84% capacitance after 10,000 charge–discharge cycles. Benefited from the synergistic effect between CeS2and ZnS QDs, the significantly improved electrochemical performance of the composite material suggests a promising strategy for designing rare-earth and QD-based advanced energy storage materials.
研究领域:
材料科学
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纳米技术
·
电化学
·
储能
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DOI
高影响因子
BIOPHARMACEUTICS & DRUG DISPOSITION
·
2022
·Vol. 43
·期 6
·247-254
·
IF 1.831
Ting Zhu,Yu Wu,Xue-Mei Li,Yu-Meng Jia,Huan Zhou,Li-Ping Jiang,Ting Tai,Qiong-Yu Mi,Jin-Zi Ji,Hong-Guang Xie
As an analog of clopidogrel and prasugrel, vicagrel is completely hydrolyzed to intermediate thiolactone metabolite 2-oxo-clopidogrel (also the precursor of active thiol metabolite H4) in human intestine, predominantly by AADAC and CES2; however, other unknown vicagrel hydrolases remain to be identified. In this study, recombinant human Raf kinase inhibitor protein (rhRKIP) and pooled human intestinal S9 (HIS9) fractions and microsome (HIM) preparations were used as the different enzyme sources; prasugrel as a probe drug for RKIP (a positive control), vicagrel as a substrate drug of interest, and the rate of the formation of thiolactone metabolites 2-oxo-clopidogrel and R95913 as metrics of hydrolase activity examined, respectively. In addition, an IC 50 value of inhibition of rhRKIP-catalyzed vicagrel hydrolysis by locostatin was measured, and five classical esterase inhibitors with distinct esterase selectivity were used to dissect the involvement of multiple hydrolases in vicagrel hydrolysis. The results showed that rhRKIP hydrolyzed vicagrel in vitro, with the values of K m , V max , and CL int measured as 20.04 ± 1.99 μM, 434.60 ± 12.46 nM/min/mg protein, and 21.69 ± 0.28 ml/min/mg protein, respectively, and that an IC 50 value of locostatin was estimated as 1.24 ± 0.04 mM for rhRKIP. In addition to locostatin, eserine and vinblastine strongly suppressed vicagrel hydrolysis in HIM. It is concluded that RKIP can catalyze the hydrolysis of vicagrel in the human intestine, and that vicagrel can be hydrolyzed by multiple hydrolases, such as RKIP, AADAC, and CES2, concomitantly.
研究领域:
药理学
·
生物化学
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DOI
高影响因子
ANALYTICAL LETTERS
·
2023
·
IF 2
Jia Song,Jiaying Yu,Kai Sun,Zhixin Chen,Xiaoxiao Xing,Yumeng Yang,Chunyu Sun,Zhifei Wang
Given the important role of carboxylesterase 2 (CES2) in the metabolism of various esters, it is of significance to develop a tool to determine endogenous CES2 activity in a rapid and highly selective manner. In this work, an "off-on" rhodamine-based fluorescent probe is reported as an effective tool for CES2 activity. Based on the substrate recognition preference of CES2 (large alcohol and small acyl groups), the probe with dimethyl carbamate as the recognition group performs well in terms of selectivity and sensitivity to CES2. The fluorescence switching control of the probe for CES2 was achieved by using the spirolactone structure of rhodamine. The probe shows the fast generation of a fluorescence signal at 634 nm upon hydrolysis of CES2 with excitation at 578 nm. The results showed a linear relationship between the fluorescence intensity at 634 nm and the CES2 activity from 0 to 4 μg/mL. The probe reacts rapidly with CES2, and the reaction is stable within 40 minutes. The probe is highly selective for CES2, with a detection limit as low as 0.303 μg/mL. In addition, the probe has currently been successfully utilized to evaluate CES2 activity in living cells. Hence, this probe is anticipated to be significant in identifying endogenous CES2 activity in intricate biological settings.
研究领域:
生物化学
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分析化学
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分子生物学
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细胞生物学
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DOI
高影响因子
MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 6
·1-10
·
IF 6.232
Liu Xingyu,Li Xiangqian,Dong Pei,Wu Zhiming,Gao Jinwei,Wang Qianming
A low-molecular-weight molecule (4-(2-(3-(dicyanomethyl)-5,5-dimethylcyclohex-1-en-1-yl)vinyl)phenyl-benzoate, DDPB) has been developed. The organic framework possesses very weak fluorescence . The feasibility of the signal transduction has been performed via fluorometric titrations in solution. DDPB gives rise to responses to carboxylesterase 2 (CES2) based on “off-on” responses. The red emission at 670 nm has been derived from the enzyme-induced hydrolysis of ester linkages, thus suppressing the intramolecular charge transfer (ICT) effect and thereby generating the fluorescent segment. The optical excitation window for this probe is extended to the visible light range ( λ ex = 516 nm), and it will induce less harmful influence on biological substances. The detection limit for the measurement of CES2 concentration is as low as 2.33 mU/mL. The conventional studies concerning the activation process are generally performed within only a single liveing cell system. In this study, it is the first time that expression of carboxylesterase 2 in five kinds of cell lines (HeLa > C1498 > active T cell > Jurkat > unactive T cell) has been clarified by flow cytometry, Western blotting, and confocal microscopy analysis. The elucidation of CES2 and its variability in a variety of cells will open new ways for drug metabolism and disease prevention.
We reported a new “substrate-mediated light-on” strategy based on an ester bond cleavage reaction. Most of prepared nanomaterials and organic fluorophores possessed short wavelength emissions in the blue or green region which will not be difficult for cellular imaging. In this study, a novel functional molecule (DDPB) was considered as the substrate for CES2 and the optical “off-on” response was realized. DDPB was cell permeable and possessed very low cytotoxicity. Moreover, the identification of CES2 and their subtle changes in five different cells afforded the sequence for carboxylesterase-2 as Hela > C1498 > Active T cell > Jurkat > Unactive T cell. Inhibition studies showed that the hydrolysis of DDPB was effectively suppressed by bis-p-nitrophenyl phosphate and the cellular tracking results firmly supported this point. To our knowledge, the inter-individual variability for the CES2 expressions in five different cell lines has never been reported via the substrate induced optical changes.
研究领域:
生物技术
·
药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2022
·Vol. 148
·期 4
·876-887
·
IF 5.227
Zhixin Chen,Jiaying Yu,Kai Sun,Jia Song,Lucheng Chen,Yong Jiang,Zhifei Wang
In vivo selective fluorescence imaging of carboxylesterase 2 (CES2) remains a great challenge because existing fluorescence probes can potentially suffer from interference by other hydrolases. In addition, some fluorescent probes that have been separately reported for measuring CES2 activity in vitro are affected by autofluorescence and absorption of the biological matrix due to their limited emission wavelength or short Stokes shift. Herein, based on the substrate preference and catalytic performance of CES2, a novel and NIR fluorescent probe was developed, in which a hemi-cyanine dye ester derivative was used as the basic fluorescent group. In the presence of CES2, the probe was hydrolyzed to expose the fluorophore CZX-OH (λabs ∼ 675 nm, λem ∼ 850 nm), which led to a notable red-shift in the fluorescence (∼175 nm) spectrum. Confocal imaging of cells and live mice demonstrated that the fluorescent signal of this probe was related to the real activities of CES2 in cancer cells. All these results will powerfully promote the screening of CES2 regulators and the analysis of CES2-related physiological and pathological processes.
研究领域:
生物化学
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分子生物学
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药理学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2023
·
IF 2.8
Qingfeng Xie,Zhuo Cao,Weiling You,Xiaoping Cai,Mei Shen,Zhangyong Yin,Yiwei Jiang,Xin Wang,Siyu Ye
New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.
研究领域:
肿瘤学
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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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DOI
PubMed
高影响因子
Cell Reports Physical Science
·
2026
·
IF 6.9
Dian Jiao,Tao Wang,Yinghou Wang,Zhengdi Ma,Mingjia Sun,Chen Meng,Weihua Chen,Yaqi Wang,Yanxin Li,Yaru Song,Xinnan Hou,Zhong Wen,Jingdong Xiao,Zhonggui He,Tianhong Zhang,Jin Sun,Zhenbao Li,Qikun Jiang
Albumin-based drug-delivery systems garner attention due to their inherent biocompatibility and tumor-targeting potential. However, they are limited by weak human serum albumin (HSA) affinity for drugs like camptothecin (CPT). To address this, we synthesize five CPT prodrug derivatives (CPT-SA-C6–C14) with tunable aliphatic alcohol chains as HSA-binding motifs and a succinic acid linker for carboxylesterase (CES1/CES2)-mediated cascade activation. CPT-SA-C10, C12, and C14 achieve ultrahigh drug loading (>30%) in albumin nanoparticles (ANPs) via enhanced HSA affinity. Aliphatic chain length shows an inverted V-shaped correlation with both HSA-binding affinity and CES1-catalyzed hydrolysis. The resulting intermediate is hydrolyzed by CES2 to release CPT. CPT-SA-C12 ANPs exhibit the highest albumin affinity and fastest enzymatic conversion, yielding superior therapeutic efficacy and favorable tolerability. This work elucidates the structure-activity relationship of albumin-bound prodrugs and advances the design of CES-responsive nanomedicines.
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DOI
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2026
·
IF 10.4
Jiang Huan-guo,Zhan Zhi-kun,Tian Ling-min,Chen Yu-lian,Cai Mei-qun,Ge Guang-bo,Chen Xin,Wei Chuan-liang,Tang Lan
Carboxylesterases CES1 and CES2 are the pivotal hepatic enzymes involved in triglyceride (TG) hydrolysis and prodrug metabolism, yet their expression and activity are suppressed in metabolic dysfunction-associated steatotic liver disease (MASLD). Liver X receptor alpha (LXRα) is known to play a crucial role in maintaining the constitutive expression of CES1 in human liver cells. Oridonin (ORI) is a diterpene derived from a traditional Chinese herb that possesses antitumor, anti-inflammatory, and antimicrobial activities. We previously demonstrated that ORI, as a natural LXRα agonist, activated the LXRα-ATGL/EPT1 pathway, correcting the TG/phosphatidylethanolamine (PE) lipid imbalance induced by obesity and thereby improving MASLD. Here, we investigated the regulatory role of LXRα on CES1/CES2 expression in MASLD liver and elucidated the underlying molecular mechanisms of ORI’s lipid-lowering effects. A high-fat diet (HFD)-induced steatosis model was established in mice. The mice were treated with ORI (100 mg·kg − 1 ·d − 1 , i.g.) from the 16th to the 24th week. RNA-seq analysis in MASLD patients demonstrated that LXRα is a key transcriptional regulator of CES1 and CES2. LXRα knockout (LXRα − / − ) mice exhibited aggravated HFD-induced steatosis and impaired metabolic conversion of the CES1/CES2 substrates, oseltamivir and irinotecan. This deficiency resulted in a corresponding increase in their drug exposure (AUC) by 154.5% and 26.2%, respectively. Mechanistically, LXRα directly bound to liver X receptor response elements (LXREs) in the promoter regions of CES1 (−183/−165 bp) and CES2 (−1870/−1852 bp) to drive transcription in HepG2 cells. Furthermore, ORI (2.5, 5, 10 μM) dose-dependently restored CES1/CES2 expression and activity, reducing lipid accumulation. Silencing of CES1 or CES2 abolished ORI’s lipid-lowering effect, confirming their essential roles. These findings establish the LXRα-CES1/CES2 pathway as a pivotal node integrating hepatic lipid homeostasis and drug metabolism, positioning ORI as a promising therapeutic agent for MASLD.
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2025
·
IF 3.8
Lu Meijun,Zhao Chen,Ma Mo,Shi Hui,Lu Mingming,Tian Yuan,Song Daqian,Zhang Ziwei
The abnormally high expression of glutathione (GSH) in hepatocellular carcinoma (HCC) cells significantly contributes to chemotherapy resistance by neutralizing reactive oxygen species (ROS). To address this problem, we developed a nanocomposite probe (micelle@PDA@MnO 2 NPs) which was composed of free radical-labeled micelles as the core, polydopamine (PDA) as the inner shell and MnO 2 nanosheets as the outer shell. In the HCC microenvironment, the over-expressed GSH triggered the decomposition of the MnO 2 shell, releasing Mn 2+ ions, and subsequently, the acidic condition and over-expressed carboxylesterase 2 (CES2) worked together to mediate the controlled release of nitroxide free radicals (i.e., TEMPONE) from the micelle core. With the help of dual-signal electron spin resonance (ESR) detection, it was found that much more free radicals and Mn 2+ were released in hepatoma cells than in normal liver cells, rendering the proposed nanotherapeutic platform specific to HCC and a good candidate for free radical therapy and chemodynamic therapy (CDT). Moreover, the therapy featured an intelligent self-amplified property: the abundant GSH in the tumor microenvironment rapidly activated the decomposition of the nanocomposite and triggered the release of free radical TEMPONE and Mn 2+ , and TEMPONE and Mn 2+ further amplified the oxidative stress to induce tumor apoptosis via ROS generation and GSH depletion. Finally, in combination with three therapy modes (Mn 2+ -mediated CDT, the oxidative stress enhancement effect of TEMPONE, and PDA-based photothermal therapy), significant therapeutic effects including facilitation of HepG2 cell apoptosis and inhibition of tumor growth in the HCC mouse model were achieved.
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY IN VITRO
·
2024
·
IF 2.6
Jia-hong Liang,Xiao-lei Yi,Jia-min Gong,Zuo Du
Gout is an immune-metabolic disease that frequently coexists with multiple comorbidities such as chronic kidney disease, cardiovascular disease and metabolic syndrome, therefore, it is often treated in combination with these complications. The present study aimed to evaluate the inhibitory effect of antigout drugs (allopurinol, febuxostat, topiroxostat, benzbromarone, lesinurad and probenecid) on the activity of the crucial phase I drug-metabolizing enzymes, carboxylesterases (CESs). 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) were utilized as the probe reactions to determine the activity of CES1 and CES2, respectively, through in vitro culturing with human liver microsomes. Benzbromarone and lesinurad exhibited strong inhibition towards CESs with Ki values of 2.16 and 5.15 μM for benzbromarone towards CES1 and CES2, respectively, and 2.94 μM for lesinurad towards CES2. In vitro-in vivo extrapolation (IVIVE) indicated that benzbromarone and lesinurad might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CESs. In silico docking showed that hydrogen bonds and hydrophobic interactions contributed to the intermolecular interactions of antigout drugs on CESs. Therefore, vigilant monitoring of potential drug-drug interactions (DDIs) is imperative when co-administering antigout drugs in clinical practice.
研究领域:
药理学
·
临床药理学
·
药物代谢
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）