MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 8
·1-11
·
IF 5.833
Feng Jun,Lu Hao,Yang Yu,Huang Wenyi,Cheng Hao,Kong Hongxing,Li
Lijun
By in situ synthesis of gold nanoparticles (AuNPs) within the acid-etched (AE) MIL-101 (Cr) framework, AE-MIL-101 (Cr) nanocomposites embedded with AuNPs (AuNP/AE-MIL-101 (Cr)) were prepared as surface-enhanced Raman scattering (SERS) substrate. AuNPs are uniformly distributed and stabilized inside the metal-organic framework (MOF), thus forming more SERS hotspots. The SERS performance of AuNP/AE-MIL-101 (Cr) was evaluated using 4-mercaptophenylboronic acid (4-MPBA), 4-mercaptobenzoic acid (4-MBA), benzidine, and rhodamine 6G (R6G). The SERS substrate displays satisfying stability with very low background signal. When benzidine is used as the Raman reporter, the limit of detection (LOD) can reach 6.7 × 10 −13 mol·L −1 , and the relative standard deviation (RSD) of the intra- and inter-batch repetitive tests is less than 5.2%. On this basis, we developed a method for the detection of human carboxylesterase 1 (hCE 1) in human serum using AuNP/AE-MIL-101 (Cr) nanocomposite as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as SERS marker. This method was used to determine hCE 1 in clinical serum samples without complicated sample pretreatment, and the detection results were consistent with the data determined by ELISA. In the concentration range 0.1–120 ng·mL −1 , the SERS signal intensity of benzidine at 1609 cm −1 gradually decreases with the increase of hCE 1 concentration (R 2 = 0.9948). The average recoveries of hCE 1 in human serum are in the range 84 to 108%, with RSDs lower than 7.7%. Graphical abstract
By using AuNP/acid etching-MIL-101(Cr) metal organic framework (MOF) as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as the SERS marker, a rapid and sensitive method for the determination of human carboxylesterase 1 (hCE1) in human serum samples has been developed.
研究领域:
分析化学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2025
·Vol. 56
·期 3
·1-14
·
IF 2.2
Wen Jingli,Geng Lei,Wang Ruohan,Zhang Xiaolei,Sui Yanmin,Liu Xiaofang,Han Xin
Breast cancer is a common malignancy in women, and it has an absence of effective therapies. Carboxylesterase 1 (CES1), a member of the carboxylesterase family, has anti-tumor properties in several types of cancer. However, the function of CES1 in breast cancer remains unclear. Peroxisome proliferator-activated receptor gamma (PPARG) is a downstream regulator of CES1 and exhibits anti-breast cancer properties. Both CES1 and PPARG were downregulated in breast cancer tissues. Low CES1 and PPARG expression were linked to poorer breast cancer survival. We constructed CES1 knockdown and overexpression models of breast cancer cells by CES1 overexpressing plasmids and plasmids containing short hairpin RNA. High expression of CES1 inhibited breast cancer cell proliferation, evidenced by diminished cell viability, decreased DNA replication, and G1 phase arrest. CES1 overexpression decreased the protein levels of CDK2, CDK6 and cyclin B1 in breast cancer cells. CES1 inhibited the Bcl-2/Bax axis and increased Cleaved caspase-3 levels. Transwell assays showed that CES1 inhibited cell migration and invasion. CES1 increased E-cadherin protein expression and decreased Vimentin protein expression. CES1 knockdown facilitated the proliferation, migration, and invasion of breast cancer cells. CES1 was found to regulate PPARG expression in breast cancer cells positively. We transfected PPARG-interfering plasmids into breast cancer cells with CES1 overexpression. Inhibition of PPARG abrogated the anti-growth and anti-metastasis functions of CES1 in breast cancer cells. This study elucidates that CES1 inhibits the malignant progression of breast cancer by up-regulating the expression of PPARG. Graphical
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Shuai Ji,Xian Shao,Zhen-yu Su,Lei Ji,Yu-jie Wang,Yun-su Ma,Lu Zhao,Yan Du,Meng-zhe Guo,Dao-quan Tang
Fufang Danshen Dripping Pill (FDDP) and Clopidogrel Bisulfate Tablet (CBT) are usually combined for treatment of coronary artery diseases in clinical. To investigate the pharmacokinetic interaction between FDDP and CBT after oral administration of FDDP, CBT and their combination in rats, a novel LC–MS method with segmented scan modes (multiple reaction monitoring and selected ion monitoring) and polarity (positive and negative ionization) was developed. Clopidogrel and the main active ingredients of FDDP, with different chemical and ionization properties, were simultaneously quantified in plasma in a single run. The method was validated in terms of specificity, linearity, precision, accuracy, recovery, matrix effect and stability. As a result, co-administration of FDDP and CBT significantly altered the pharmacokinetic parameters of danshensu, ginsenoside Rb1, dihydrotanshinone I, tanshinone I and tanshinone IIA of FDDP, as well as clopidogrel. Mechanism studies suggested that induction of liver cytochrome P450 isozymes CYP2C11 and CYP3A1 by co-administration, as well as inhibition of carboxyl esterase 1, was partly responsible for FDDP-CBT pharmacokinetic interactions. The developed LC–MS method could be used to simultaneously quantify different types of in vivo analytes in a single run, and the results could be used for clinical medication guidance of FDDP and CBT.
研究领域:
药理学
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分析化学
·
药学
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产品关联
DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2019
·Vol. 47
·期 8
·794-801
·
IF 3.354
Hongwei Yao,Ruifeng Bai,Tianming Ren,Yani Wang,Jingkai Gu,Yingjie Guo
Clopidogrel (Clop), a thienopyridine antiplatelet prodrug, is metabolized by cytochrome P450s (CYPs) to an active metabolite, Clop-AM, and hydrolyzed by carboxylesterase (CES)1 to the inactive Clop-acid. Patients with type 2 diabetes (T2DM) tend to have a poor response to Clop due to reduced generation of Clop-AM. Whether a similar response occurs in the Zucker diabetic fatty (ZDF) rat, a commonly used animal model of T2DM, has not been explored. In this work, we compared ZDF and control rats for hepatic CES1- and CYP-mediated Clop metabolism; pharmacokinetics of Clop, Clop-AM, and Clop-acid; and the antiplatelet efficacy of Clop. In contrast to clinical findings, Clop-treated ZDF rats displayed significantly less (50%) maximum platelet aggregation at 4 hours than control rats; the enhanced efficacy was accompanied by higher formation of Clop-AM and lower formation of Clop-acid. In vitro studies showed that hepatic levels of CES1 protein and activity and Ces1e mRNA were significantly lower in ZDF than in control rats, as were the mRNA levels of CYP2B1/2, CYP2C11, and CYP3A2, and levels of CYP2B6-, CYP2C19-, and CYP3A4-related proteins and enzymatic activities in liver microsomes of ZDF rats. Interestingly, liver microsomes of ZDF rats produced higher levels of Clop-AM than that of control rats despite their lower CYP levels, although the addition of fluoride ion, an esterase inhibitor, enhanced Clop-AM formation in control rats more than in ZDF rats. These results suggest that the reduction in CES1-based Clop inactivation indirectly enhances Clop efficacy in ZDF rats by making more Clop available for CYP-mediated Clop-AM formation.
研究领域:
药理学
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糖尿病研究
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代谢
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药物动力学
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Xiaoting Luo,Feifei Lu,Zhiyue Yin,Zhiyun Zhou,Zhongmin Wang,Hongjian Zhang
Carboxylesterase 1 (CES1) is a hydrolytic enzyme that plays an important role in the activation or deactivation of many therapeutic agents, thus affecting their pharmacokinetic and pharmacodynamic outcomes. Using rat liver S9 as an enzyme source and enalapril as a CES1 substrate, the present study examined effects of a number of flavonoids on the formation of enalaprilat (the active form of enalapril) produced by CES1-mediated hydrolysis. While a majority of flavonoids tested showed inhibition on CES1, an unexpected hormetic effect was observed for epigallocatechin (EGC) and epigallocatechin gallate (EGCG), i.e., stimulatory effect at low concentrations and enzyme inhibition at high concentrations. Further experiments revealed that oxidative stress caused by hydrogen peroxide, arachidonic acid plus iron, and oxidized low density lipoproteins (oxLOL) reduced CES1 activity in rat liver S9 and the loss of CES1 enzyme activity could be rescued largely by EGC or EGCG. In contrast, such effects were minimal in human liver S9, probably due to the presence of a higher ratio of reduced vs oxidized forms of glutathione . The above findings suggest that the polyphenolic nature of EGC or EGCG might be responsible for rescuing CES1 activity under oxidative stress. Because of the importance of CES1 in drug activation or deactivation and rat liver S9 as a versatile in vitro system used for drug metabolism studies and drug safety assessment , caution should be exercised to avoid potential biases for data interpretation and decision making when CES1 activity in rat liver S9 is evaluated with dependency on experimental conditions.
研究领域:
药理学
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毒理学
·
生物化学
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药物代谢
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酶学
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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）