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ANALYTICA CHIMICA ACTA · 2025 · IF 6

Development of a natural porcine-estrogen-receptor-based pseudo immunoassay for screening of 13 estrogens in milk and studying its recognition mechanism

Zu Qiang Jiang,Jian Ping Wang,Peng Lei Cui

Background There have been some immunoassays reported for screening of the residues of estrogens in milk, but these methods can only determine one drug because of the limited recognition abilities of the used antibodies. Due to the broad specific recognition ability, receptor can be used as “special antibody” to develop pseudo immunoassay. However, there has been no article reporting the use of estrogen receptor for determination of estrogens in foods of animal origin so far. Furthermore, the recognition mechanism of estrogen receptor for estrogens have not been thoroughly studied. Results In this study, a type of magnetic probe based on 17β-estradiol was synthesized that was used to produce the natural porcine estrogen receptor with ovarian as the source tissue. Then its recognition mechanisms for 13 estrogens were studied based on the optimal homological model. Results showed it only interacted with estrogens but did not interact with other steroid hormones. Then it was utilized as a broad specific recognition reagent to develop a direct competitive method on 96-well microplate for detection of the 13 drugs in milk. Due to the utilization of streptavidin-biotin labeled horseradish peroxidase as signal amplification system, the sensitivities for the 13 estrogens (limits of detection 0.007-0.0573 ng/mL) were improved for 33-100 folds in comparison with the use of conventional horseradish peroxidase system (limits of detection 0.31-3.53 ng/mL). This method showed no cross-reactivity with other steroid hormones, consistent with the docking result. Significance This is the first study reporting the use of magnetic probe to produce natural receptor from animal tissues, and this is also the first study reporting a natural estrogen-receptor-based method for multi-determination of estrogens in food sample. With the guidance of this study, more receptors and related analytical methods for other drugs or small molecules maybe are reported in the future.

CAS / MDL: 56-53-1
研究领域: 食品安全 · 生物化学 · 药物分析
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CIRCULATION RESEARCH · 2016 · IF 11.551

The Expanding Complexity of Estrogen Receptor Signaling in the Cardiovascular System

Sara Menazza,Elizabeth Murphy

Estrogen has important effects on cardiovascular function including regulation of vascular function, blood pressure, endothelial relaxation, and the development of hypertrophy and cardioprotection. However, the mechanisms by which estrogen mediates these effects are still poorly understood. As detailed in this review, estrogen can regulate transcription by binding to 2 nuclear receptors, ERα and ERβ, which differentially regulate gene transcription. ERα and ERβ regulation of gene transcription is further modulated by tissue-specific coactivators and corepressors. Estrogen can bind to ERα and ERβ localized at the plasma membrane as well as G-protein–coupled estrogen receptor to initiate membrane delimited signaling, which enhances kinase signaling pathways that can have acute and long-term effects. The kinase signaling pathways can also mediate transcriptional changes and can synergize with the ER to regulate cell function. This review will summarize the beneficial effects of estrogen in protecting the cardiovascular system through ER-dependent mechanisms with an emphasis on the role of the recently described ER membrane signaling mechanisms.

研究领域: 医学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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International Journal of Genomics · 2020 · IF 2.414

The Analysis of Estrogen-Degrading and Functional Metabolism Genes in Rhodococcus equi DSSKP-R-001

Kejian Tian,Fanxing Meng,Qi Meng,Yan Gao,Lili Zhang,Le Wang,Yuqing Wang,Xue Li,Hongliang Huo

Estrogen contamination is recognized as one of the most serious environmental problems, causing widespread concern worldwide. Environmental estrogens are mainly derived from human and vertebrate excretion, drugs, and agricultural activities. The use of microorganisms is currently the most economical and effective method for biodegradation of environmental estrogens. Rhodococcus equi DSSKP-R-001 (R-001) has strong estrogen-degrading capabilities. Our study indicated that R-001 can use different types of estrogen as its sole carbon source for growth and metabolism, with final degradation rates above 90%. Transcriptome analysis showed that 720 (E1), 983 (E2), and 845 (EE2) genes were significantly upregulated in the estrogen-treated group compared with the control group, and 270 differentially expressed genes (DEGs) were upregulated across all treatment groups. These DEGs included ABC transporters; estrogen-degrading genes, including those that perform initial oxidation and dehydrogenation reactions and those that further degrade the resulting substrates into small molecules; and metabolism genes that complete the intracellular transformation and utilization of estrogen metabolites through biological processes such as amino acid metabolism, lipid metabolism, carbohydrate metabolism, and the tricarboxylic acid cycle. In summary, the biodegradation of estrogens is coordinated by a metabolic network of estrogen-degrading enzymes, transporters, metabolic enzymes, and other coenzymes. In this study, the metabolic mechanisms by which Rhodococcus equi R-001 degrades various estrogens were analyzed for the first time. A new pollutant metabolism system is outlined, providing a starting point for the construction of engineered estrogen-degrading bacteria.

CAS / MDL: 53-16-7 50-28-2 57-63-6
研究领域: 微生物学 · 环境科学 · 基因组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CHROMATOGRAPHY A · 2020 · IF 4.049

Magnetic solid-phase extraction modified Quick, Easy, Cheap, Effective, Rugged and Safe method combined with pre-column derivatization and ultra-high performance liquid chromatography-tandem mass spectrometry for determination of estrogens and estrogen mimics in pork and chicken samples

Xiang Xiong,Dan Li,Zhifeng Du,Chaomei Xiong,Hongliang Jiang

In this study, conventional Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method was modified by magnetic solid-phase extraction (MSPE) for purification/pre-concentration of eleven estrogens and estrogen mimics from the extracts of pork and chicken muscles, prior to dansyl chloride (DNS-Cl) derivatization coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay. Dual octadecyl- and 2-aminoethyl-3-aminopropyl- groups functionalized mesoporous silica core-shell magnetic nanoparticles (C 18 /NH 2 -Fe 3 O 4 @mSiO 2 MNPs) were synthesized and employed as MSPE sorbent with remarkable aqueous compatibility in comparison with conventional C 18 functionalized sorbent. The proposed MSPE is easier to handle than the traditional SPE purification process in QuEChERS method. The lab-prepared MNPs were characterized by transmission electron microscope (TEM), brunner-emmet-teller (BET), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA) and vibrating sample magnetometer (VSM). Pre-column derivatization was conducted to significantly enhance the sensitivity of the analytes in MS/MS via analyzing their derivatives in positive ion mode instead of analyzing their original forms in negative ion mode. Under the optimal sample pretreatment and instrumental analysis conditions, the approach showed low limits of detection (LODs, 0.02‒3.00 µg kg –1 ), appropriate recoveries (81.1‒115.4%) and acceptable precisions (0.48‒15.1%, n  = 6), with good feasibility and future prospect of trace compounds analysis in complex food samples.

研究领域: 分析化学 · 食品安全 · 环境科学
✓ 已验证 DOI 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2019 ·Vol. 20 ·期 3 ·744 · IF 4.183

Multi-Residue Method for the Analysis of Stilbene Estrogens in Milk

Tianzhu Guan,Yonghai Sun,Yongjun Wang,Zhuolin Li,Tiezhu Li,Ligang Hou

The rapid analysis of stilbene estrogens is crucially important in the environment, food and health sectors, but quantitation of lower detection limit for stilbene estrogens persists as a severe challenge. We herein described a homologous and sensitive fluorescence polarization (FP) assay based on estrogen receptor α ligand binding domain (ER-LBD) to monitor stilbene estrogens in milk. Under optimal conditions, the half maximal inhibitory concentrations (IC50) of the FP assay were 9.27 nM, 12.94 nM, and 22.38 nM for hexestrol, dienestrol and diethylstilbestrol, respectively. And the corresponding limits of detection (LOD) values were 2.94 nM, 2.89 nM, and 3.12 nM. Finally, the assay was applied to determine the stilbenes in milk samples where the mean recoveries ranged from 95.76% to 112.78% and the coefficients of variation (CV) below 12.00%. Furtherly, we have focused our study on high cross-reactivity phenomena by using two in silico approaches, including molecular docking analysis and topology analysis. Overall, docking results show that several residues in the hydrophobic pocket produce hydrophobic interactions with the tested drug molecules, which contribute to the stability of their binding. In this paper, we conclude that the FP method is suitable for the rapid detection of stilbenes in milk samples, requiring no expensive analytical equipment or time-consuming sample preparation. This work offers a practical approach that applies bioscience technology in food safety testing and improves analytical speed and laboratory efficiency.Keywords:Estrogen receptor α ligand binding domain (ER-LBD);stilbene estrogens;fluorescence polarization;molecular docking

CAS / MDL: 84-16-2
研究领域: 食品安全检测 · 生物科学技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biology of Sex Differences · 2020 ·Vol. 11 ·期 1 ·1-13 · IF 3.267

Estrogen modulation of pain perception with a novel 17β-estradiol pretreatment regime in ovariectomized rats

Zhang Wenxin,Wu Hui,Xu Qi,Chen Sheng,Sun Lihong,Jiao Cuicui,Wang Luyang,Fu Feng,Feng Ying,Qian Xiaowei,Chen Xinzhong

Estrogen plays substantial roles in pain modulation; however, studies concerning sex hormones and nociception often yield confusing results. The discrepancy could be a result of lack of consensus to regard estrogen as a variable when working with animal models; thus, the influence of hormones’ fluctuations on nociception has continually been neglected. In the present study, we designed a novel hormone substitution model to aid us to evaluate the effects of estrogen’s long-term alterations on ovariectomy (OVX)-induced mechanical hyperalgesia and the expression of estrogen receptors(ERs). OVX rats were implanted with slow-release estrogen pellets at differently arranged time points and doses, such that a gradual elevation or decrease of serum estrogen levels following a relatively stable period of estrogen replacement was achieved in rats. Our results demonstrated that gradual estrogen depletion rather than elevation following the stable period of estrogen substitution in OVX rats alleviated OVX-induced mechanical hyperalgesia in a dose-independent manner, and the opposite estrogen increase or decrease paradigms differently regulate the expression of spinal ERs. Specifically, in rats rendered to continuously increased serum estrogen, the early phase estrogen-induced anti-nociception effect in OVX rats was eliminated, which was accompanied by an over-activation of ERα and a strong depression of ERβ, while in the OVX rats subject to gradual decrease of estrogen replacement, both ERα and ERβ increased modestly compared with the OVX group. Thus, the present study demonstrated that estrogen increase or decrease modulate nociception differently through change of spinal ERs.

研究领域: 神经科学 · 内分泌学 · 疼痛研究
✓ 已验证 DOI PubMed 高影响因子
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Foods · 2022 ·Vol. 11 ·期 9 ·1178 · IF 5.561

Screening of Estrogenic-Disrupting Compounds in Dairy Products Based on the Estrogen Receptor Cocktail

Xiaoqi Li,Shuyuan Du,Fangyuan Tian,Minglu Wang,Ying Wang,Hongyan Zhang,Liguo Zang

The residue of estrogenic-disrupting compounds (EDCs) that are secreted by cows, added as drugs, and present in the feed may exist in dairy products. A gold nanoparticles (AuNPs)-estrogen receptor (ER) cocktail colorimetric assay equipped with ER cocktail solid phase extraction (SPE) was established to screen EDCs. Nine EDCs with high, moderate, and low estrogenic activity were selected to be the representative targets. The recognition range of the colorimetric assay combined with the ER cocktail SPE was wider than that of a single ERα or ERβ. The lowest detection limit of the established assay was about 10−9mg·mL−1. The detection limits of estrone, bisphenol A, and bisphenol B were about one order of magnitude lower than the method based on a single ER. The recoveries of the spiked nine EDCs were between 80.0% and 110.0%, and daidzein was identified in the dairy product. The developed method has potential application prospects in food safety and environmental monitoring.Keywords:estrogenic-disrupting compounds;estrogen receptor cocktail;solid phase extraction;gold nanoparticles colorimetric assay;dairy products

CAS / MDL: 80-05-7 2971-36-0
研究领域: 食品安全 · 环境监测 · 分析化学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NUCLEIC ACIDS RESEARCH · 2020 ·Vol. 48 ·期 19 ·10768-10784 · IF 11.502

An H3K4me3 reader, BAP18 as an adaptor of COMPASS-like core subunits co-activates ERα action and associates with the sensitivity of antiestrogen in breast cancer

Sun Ge,Wang Chunyu,Wang Shengli,Sun Hongmiao,Zeng Kai,Zou Renlong,Lin Lin,Liu Wei,Sun Ning,Song Huijuan,Liu Wensu,Zhou Tingting,Jin Feng,Shan Zhongyan,Zhao Yue

Estrogen receptor alpha (ERα) signaling pathway is essential for ERα-positive breast cancer progression and endocrine therapy resistance. Bromodomain PHD Finger Transcription Factor (BPTF) associated protein of 18kDa (BAP18) has been recognized as a crucial H3K4me3 reader. However, the whole genomic occupation of BAP18 and its biological function in breast cancer is still elusive. Here, we found that higher expression of BAP18 in ERα-positive breast cancer is positively correlated with poor prognosis. ChIP-seq analysis further demonstrated that the half estrogen response elements (EREs) and the CCCTC binding factor (CTCF) binding sites are the significant enrichment sites found in estrogen-induced BAP18 binding sites. Also, we provide the evidence to demonstrate that BAP18 as a novel co-activator of ERα is required for the recruitment of COMPASS-like core subunits to the cis-regulatory element of ERα target genes in breast cancer cells. BAP18 is recruited to the promoter regions of estrogen-induced genes, accompanied with the enrichment of the lysine 4-trimethylated histone H3 tail (H3K4me3) in the presence of E2. Furthermore, BAP18 promotes cell growth and associates the sensitivity of antiestrogen in ERα-positive breast cancer. Our data suggest that BAP18 facilitates the association between ERα and COMPASS-like core subunits, which might be an essential epigenetic therapeutic target for breast cancer.

研究领域: 肿瘤学 · 分子生物学 · 表观遗传学 · 癌症治疗
✓ 已验证 DOI PubMed 高影响因子
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Nature Communications · 2017 ·Vol. 8 ·期 1 ·1-13 · IF 12.124

Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice

Zhang Zhaobin,Hu Ying,Guo Jilong,Yu Tong,Sun Libei,Xiao Xuan,Zhu Desheng,Nakanishi Tsuyoshi,Hiromori Youhei,Li Junyu,Fan Xiaolin,Wan Yi,Cheng Siyu,Li Jun,Guo Xuan,Hu Jianying

Bisphenol A (BPA) is used in the production of plastic but has oestrogenic activity. Therefore, BPA substitutes, such as fluorene-9-bisphenol (BHPF), have been introduced for the production of so-called ‘BPA-free’ plastics. Here we show that BHPF is released from commercial ‘BPA-free’ plastic bottles into drinking water and has anti-oestrogenic effects in mice. We demonstrate that BHPF has anti-oestrogenic activity in vitro and, in an uterotrophic assay in mice, induces low uterine weight, atrophic endometria and causes adverse pregnancy outcomes, even at doses lower than those of BPA for which no observed adverse effect have been reported. Female mice given water containing BHPF released from plastic bottles, have detectable levels of BHPF in serum, low uterine weights and show decreased expressions of oestrogen-responsive genes. We also detect BHPF in the plasma of 7/100 individuals, who regularly drink water from plastic bottles. Our data suggest that BPA substitutes should be tested for anti-oestrogenic activity and call for further study of the toxicological effects of BHPF on human health.

CAS / MDL: 10540-29-1
研究领域: 环境科学 · 毒理学 · 生殖生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2020 · IF 4.192

Detection of Phytoestrogen Metabolites in Breastfed Infants’ Urine and the Corresponding Breast Milk by Liquid Chromatography–Tandem Mass Spectrometry

Jialing Min,Zitong Wang,Chenglin Liang,Wenjie Li,Jie Shao,Kunrui Zhu,Lu Zhou,Jing Cheng,Shihong Luo,Lehan Yu,Yudong Wu,Mingyong Xie,Xiaojuan Hu

To date, there has been limited information on phytoestrogen (PE) exposure and metabolism in breastfed infants. In the present work, 50 sample pairs of Chinese breastfed infants’ urine and the corresponding breast milk were collected. The contents of the relevant PE metabolites in the biosamples were detected via liquid chromatography–tandem mass spectrometry. The correlations between the PE metabolite contents in breastfed infants’ urine and those in the corresponding breast milk were analyzed. The average concentrations of total PE metabolites in breast milk and urine were 0.27 and 0.23 nmol/mL, respectively. Genistein and enterolactone levels in the infant urine were positively correlated with their concentrations in the corresponding breast milk samples, which implies that urine excretion can be utilized as a noninvasive parameter for precise genistein and enterolactone intake assessment. Additionally, the efficiency of PE urine excretion showed significant differences across infants with different ages, genders, and durations of pregnancy.

研究领域: 营养学 · 分析化学 · 儿科医学
✓ 已验证 DOI PubMed 高影响因子
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CHEMOSPHERE · 2018 · IF 4.427

Phototransformation of estrogens mediated by Mn(III), not by reactive oxygen species, in the presence of humic acids

Xinghao Wang,Jiayi Yao,Siyuan Wang,Xiaoxue Pan,Ruiyang Xiao,Qingguo Huang,Zunyao Wang,Ruijuan Qu

Photodegradation of pollutants is classically explained by reaction with reactive oxygen species. However Mn(III) may also remove pollutants, but direct evidence is actually lacking. Here we investigated the role of soluble Mn(III) on phototransformation of four typical estrogens, namely estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-ethynylestradiol (EE2), in the presence of Mn(II) and humic acid . Conversion rates of 60.2%, 89.0%, 87.6%, and 80.2% were achieved for E1, E2, E3, and EE2, respectively, after 72 h visible light irradiation. A detailed quenching experiments revealed that soluble Mn(III), and not reactive oxygen species, was the oxidant responsible for estrogen removal. The determination of Mn(III) concentration provided direct proof of the role of Mn(III)-based oxidizers in the conversion of estrogens. Soluble Mn(III) can form complexes with humic acid, and about 6.51 μM of Mn(III)-humic acid was formed from 20 μM of Mn(II) in the presence of 5 mg/L of humic acid. Furthermore, product identification and theoretical computation demonstrated that estrogens are mainly converted into oligomers (dimers, trimers, tetramers, etc.) via a single-electron process. According to these results, the oxidation of Mn(II) to Mn(III) is initiated by superoxide ion (O 2 •- ) generated from dissolved oxygen in the presence of humic acid under visible light irradiation. The formed soluble Mn(III) strips the estrogens of a single electron to generate phenoxyl radicals, which undergo oligomerization, while leads to regeneration of Mn(II). Hence, the photochemical Mn(II)-Mn(III) redox cycling may significantly influence the fate and transformation of estrogens in waters.

研究领域: 环境科学 · 生物学
✓ 已验证 DOI 高影响因子
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PHYTOMEDICINE · 2025 · IF 8.3

Luteolin alleviates estrogen deficiency-induced muscle atrophy via targeting SLC7A11-mediated ferroptosis

Yu Liu,Honglin Chen,Kun Chen,Qi Shang,Feng Lin,Peng Zhang,You Zhang,Weicheng Qin,Huiwen Liu,Weiyu Qiu,Xingda Chen,Yan Gong,Yixuan Jiang,Yuzhuo Zhang,Jiahui He,Wenhua Zhao,Hui Ren,Gengyang Shen,Xiaobing Jiang

Background Skeletal muscle atrophy, which is a debilitating condition exacerbated by estrogen deficiency, lacks effective therapeutic interventions. Although ferroptosis (an iron-dependent form of cell death driven by lipid peroxidation) has emerged as a contributor to muscle degeneration, its regulatory mechanisms remain poorly defined. In this study, we identified luteolin, which is a natural flavonoid, as a potent inhibitor of ferroptosis that mitigates estrogen deficiency-induced muscle atrophy by targeting SLC7A11. Purpose The aim of this study was to investigate the role of ferroptosis in the anti-muscle atrophy effects of luteolin. Methods Via database screening, luteolin was identified as a potential drug for improving muscle atrophy, and the promotion of C2C12 myogenic differentiation by luteolin was detected by using immunofluorescence (IF), quantitative reverse transcription PCR (RT-qPCR) and western blot (WB). The mechanism of luteolin-mediated ferroptosis in muscle atrophy was confirmed by RNA-seq, transmission electron microscopy (TEM), and GSH, MDA, SOD and Fe 2+ assays. Molecular docking, molecular dynamics simulation, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and siRNA-mediated gene knockout were applied to validate the notion that the mechanism of luteolin treatment of muscle atrophy involves target binding to SLC7A11. In addition, this study confirmed the role of luteolin in ameliorating muscle atrophy via the modulation of the SLC7A11-mediated ferroptosis pathway in vivo . Finally, the effect of luteolin on the myogenic differentiation of HsKMCs was investigated. Results Luteolin promotes myogenic differentiation and significantly inhibits myotube atrophy, with the main mechanism of these effects involving the direct binding of luteolin to the SLC7A11 protein to inhibit the occurrence of ferroptosis. We confirmed that luteolin can inhibit ferroptosis in muscle tissue and improve the loss of muscle mass and strength due to muscle atrophy in vivo . In addition, luteolin significantly inhibited myotube atrophy in HsKMCs and promoted their myogenic differentiation by modulating the SLC7A11-mediated ferroptosis. Conclusions Our findings demonstrate that luteolin regulates myogenesis and prevents muscle atrophy ​​through binding to SLC7A11 and subsequently inhibiting ferroptosis. This study elucidates the critical role of the SLC7A11-ferroptosis axis in preserving muscle physiology during atrophy, while identifying luteolin as a therapeutic agent capable of targeting SLC7A11 to suppress ferroptosis and alleviate muscle atrophy.

研究领域: 医学 · 分子生物学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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