Frontiers in Pharmacology
·
2022
·
IF 5.988
Wang Rulin,Yuan Tengteng,Sun Jing,Yang Menghuan,Chen Yunna,Wang Lei,Wang Yanyan,Chen Weidong,Peng Daiyin
Cholestasis, characterized by disturbance of bile formation, is a common pathological condition that can induce several serious liver diseases. As a kind of trigger, estrogen-induced cholestasis belongs to drug-induced cholestasis. Paeoniflorin is the most abundant bioactive constituent in Paeonia lactiflora Pall., Paeonia suffruticosa Andr., or Paeonia veitchii Lynch, a widely used herbal medicine for treating hepatic disease over centuries in China. However, the pharmacologic effect and mechanism of paeoniflorin on estrogen-induced cholestasis remain unclear. In this experiment, the pharmacological effect of paeoniflorin on EE-induced cholestasis in rats was evaluated comprehensively for the first time. Ultra-high-performance liquid chromatography coupled with Q-Exactive orbitrap mass spectrometer was used to monitor the variation of bile acid levels and composition. It was demonstrated that paeoniflorin alleviated 17α-ethinylestradiol (EE)-induced cholestasis dose-dependently, characterized by a decrease of serum biochemical indexes, recovery of bile flow, amelioration of hepatic and ileal histopathology, and reduction of oxidative stress. In addition, paeoniflorin intervention restored EE-disrupted bile acid homeostasis in enterohepatic circulation. Further mechanism studies using western blot, quantitative Real-Time PCR, and immunohistochemical showed that paeoniflorin could upregulate hepatic efflux transporters expression but downregulate hepatic uptake transporter expression. Meanwhile, paeoniflorin reduced bile acids synthesis by repressing cholesterol 7α-hydroxylase in hepatocytes. Paeoniflorin affected the above transporters and enzyme via activation of a nuclear receptor, farnesoid X receptor (FXR), which was recognized as a vital regulator for maintaining bile acid homeostasis. In conclusion, paeoniflorin alleviated EE-induced cholestasis and maintained bile acid homeostasis via FXR-mediated regulation of bile acids transporters and synthesis enzyme. The findings indicated that paeoniflorin might exert a potential therapeutic medicine for estrogen-induced cholestasis.
研究领域:
药理学
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肝病学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2025
·
IF 4.3
Xuena Zhang,Fengqiang Zhang,Chongwei Yin,Juan Xu,Ting Wang
Ethinylestradiol (EE) is a clinically used estrogen with antifertility effects that is poorly water soluble, limiting bioavailability and preventing long-term release when administered orally. This study addresses these challenges through the development of a novel injectable thermosensitive hydrogel that both improves hydrophobic EE dispersion and enables sustained in vivo release, presenting significant potential for long-term contraception. Carboxymethyl-β-cyclodextrin (CM-β-CD) was synthesized to encapsulate EE, thereby enhancing its solubility and distribution in the hydrogel matrix. We found that hydrogels prepared by adding 0.5% (w/v) oxidized dextran (ODex) to the chitosan/sodium β-glycerophosphate (CS/ODex/β-GP) system exhibited mechanical strength favorable for cell growth compared to conventional CS/β-GP, resolved the problems of poor stability and mechanical strength of CS/β-GP hydrogels, and ensured effective retention and delivery in vivo . A 240h drug release study demonstrated the hydrogel’s ability to sustain release, highlighting its potential to prolong contraceptive efficacy. Biocompatibility testing showed cell viability in excess of 85%. FTIR and SEM characterization further confirmed the functional structure and morphology of the hydrogel. This thermosensitive injection system provides a promising platform for the long-term release of hydrophobic drugs such as EE, providing an innovative approach to extended contraceptive delivery.
研究领域:
药剂学
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生物材料
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生殖医学
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药物递送系统
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高分子药物载体
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转化医学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2020
·
IF 6.551
Wenjing Zong,Zhaoming Guo,Minghuo Wu,Xianliang Yi,Hao Zhou,Siyuan Jing,Jingjing Zhan,Lifen Liu,Yang Liu
Endocrine-disrupting chemicals (EDCs) cause serious threats to human health. Five types of MnO 2 were synthesized and characterized. They exhibited different removal performances for three EDCs, i.e., estrone (E1), ethynylestradiol (EE2) and bisphenol A (BPA). Only δ-MnO 2 can completely remove E1 within 120 min at pH 3.0. Free Mn (III) was determined at the beginning of the reaction and participated in the EDCs removal process. Electron spin resonance (ESR) indicated that δ-MnO 2 could produce superoxide anions (·O 2 − ) and singlet oxygen ( 1 O 2 ) in the existence of methanol. The reactive oxygen species (ROS) quenching experiments showed 1 O 2 have certain contribution to the E1 removal by δ-MnO 2 . The source of ROS is mainly the lattice oxygen from δ-MnO 2 , and can be replenished through the layer structure destruction caused by the reaction between Mn(III) and E1. The ROS dependent EDCs removal by δ-MnO 2 leads to a deep understanding on this well-known oxidant.
研究领域:
环境科学
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化学工程
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水处理
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2022
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IF 16.744
Yunning Chen,Renquan Guan,Xueying Cheng,Jie Zhao,Zhengkai Wu,Yan Wang,Qingkun Shang,Yingnan Sun
In this paper, two surface oxygen vacancy-rich TiO 2 composite photocatalysts were successfully constructed by solid thermal reduction ((R-Vo)TiO 2 ) and bimetallic doping (Nd-Fe-(D-Vo)TiO 2 ). The oxygen vacancies were characterized in detail using XPS, Raman, EPR and STEM. The results show that the excellent photocatalytic performance of Nd-Fe-(D-Vo)TiO 2 deriving from its doping energy and surface oxygen vacancies. Nd-Fe-(D-Vo)TiO 2 could degrade 58 % of phenol within 120 min, which was much greater than 15 % of TiO 2 and 27 % of (R-Vo)TiO 2 . Three composite photocatalysts, TiO 2 @EA, (R-Vo)TiO 2 @EA and Nd-Fe-(D-Vo) TiO 2 @EA, with better visible light absorption and photocatalytic performance were further obtained by bonding ellagic acid (EA) to the surface of TiO 2 . Nd-Fe-(D-Vo)TiO 2 @EA could almost completely degrade ethinyl estradiol within 20 min with a high minimization degree of 84 %. The possible sites of ethinyl estradiol attacked by free radicals were predicted by theoretical calculation combining with high-resolution mass spectrometry analysis, and the possible degradation mechanism was proposed.
研究领域:
环境科学
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材料科学
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化学工程
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光化学
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产品关联
DOI
高影响因子
American Journal of Translational Research
·
2025
·Vol. 17
·期 7
·5081
·
IF 1.6
Pengyu Huang,Suhua Jiang,Beihong Zheng,Yun Fu,Wenqiang You,Haiyan Li
Objective: To evaluate the therapeutic outcomes of combining ethinylestradiol-cyproterone acetate (EE-CPA) with raloxifene in the management of polycystic ovary syndrome (PCOS)-associated infertility. Methods: The study included 115 women diagnosed with PCOS-associated infertility, admitted between January 2021 and January 2025. The participants were divided into two groups: 55 women receiving raloxifene monotherapy (control group) and 60 treated with EE-CPA plus raloxifene (observation group). The following were assessed: therapeutic effectiveness, adverse drug reactions (abdominal/pelvic pain, nausea/vomiting, body weight fluctuations, and breast tenderness), metabolic markers (fasting plasma glucose [FPG], fasting serum insulin [FINS], and homeostasis model assessment of insulin resistance [HOMA-IR]), sex hormones (estradiol [E2], follicle-stimulating hormone [FSH], and luteinizing hormone [LH]), ovarian function (ovarian volume and endometrial thickness), endometrial receptivity (resistance index [RI] and pulsatility index [PI]), and pregnancy outcomes (ovulation, miscarriage, and clinical pregnancy). Results: The combination therapy showed superior outcomes, including enhanced overall effectiveness, increased ovulation and pregnancy rates, and a reduced miscarriage rate (all P>0.05). No significant differences in adverse drug reactions were found between the two groups (P>0.05). After treatment, the observation group showed greater improvements in metabolic markers, FSH, LH, ovarian volume, RI, and PI (all P>0.05). Additionally, E2 levels and endometrial thickness were more significantly enhanced in the observation group compared to the control group (all P>0.05). Conclusions: The combination of EE-CPA and raloxifene is highly effective in managing PCOS-associated infertility, improving therapeutic outcomes without significantly increasing adverse effects. It also leads to notable improvements in metabolism, sex hormones, ovarian function, and endometrial receptivity, ultimately enhancing pregnancy outcomes.
研究领域:
妇产科学
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内分泌学
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生殖医学
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药理学
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临床研究
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 8
·4273-4283
·
IF 2.936
Si-rong Tian,Yun-guo Liu,Shao-bo Liu,Guang-ming Zeng,Lu-hua Jiang,Xiao-fei Tan,Xi-xian Huang,Zhi-hong Yin,Ni Liu,Jiang Li
With a view to reducing estrogens pollution in aqueous environments, montmorillonite/hydrochar (MMT/HC) with or without modification by KOH via hydrothermal carbonization process (HTC) were applied to remove 17β-estradiol (E2) and 17α-ethynylestradiol (EE2). The characterizations of MMT/HC indicated that MMT had been successfully attached onto HC surface, which could cause an improvement in the stability of the clay nanoparticles. MMT/HC with 1% KOH (MMT/HC-K1) exhibited excellent adsorption ability (E2: Qm = 138 mg g−1, EE2: Qm = 69 mg g−1) compared to those of other adsorbents; approximately 2-fold higher than that of HC. Moreover, the adsorption capacity maintained a high level over a wide pH range (2–8). The pseudo-second-order model and Freundlich model exhibited prior fitting performance for adsorption of E2 and EE2. The regenerated MMT/HC-K1 retained over 80% of its initial capacity after four cycles. The adsorption mechanism on MMT/HC-K1 could be explained by hydrophobicity, π–π bond, electrostatic interaction and H-bonding interaction. Overall, MMT/HC-K1 synthesis from two low-cost materials, could be considered as a competitive adsorbent for estrogens removal from aqueous environment, considering its high adsorption capacity and regeneration ability.
研究领域:
环境科学
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材料科学
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水处理
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产品关联
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Jingye Cui,Huan He,Wanqi Shi,Zhicheng Liao,Danni Cui,Jianxiang Yang,Yixin Liu,Chaochao Lai,Bin Huang,Xuejun Pan
Microbial-derived extracellular polymeric substances (EPS) and iron minerals are ubiquitous in aquatic environments, and they can influence the fate of organic micropollutants such as 17α-ethinylestradiol (EE2). However, the interactions between EPS and iron minerals, and their influence on EE2 photodegradation, are seldom addressed in the literature. This study explored the effects of EPS derived from different aerobic or anaerobic microbials on the reductive dissolution of ferrihydrite (Fhy) and subsequent EE2 photodegradation, with emphasis on the impact of Fe-EPS complexes formation. In the dark, EPS could promote the reductive dissolution of Fhy via ligand-metal charge transfer, accompanied by Fe(III)-EPS complexes formation. Irradiation could further enhance such a dissolution process. Dissolved iron could accelerate the photolysis of protein and humic substances, triggering Maillard-like reactions that form the unsaturated medium- or high-molecular-weight polymers. The aerobic-EPS containing more proteins and humic substances photodegraded EE2 more effectively than anaerobic-EPS, with the triplet excited state playing a crucial role. In contrast, Fhy inhibited EPS-mediated EE2 photodegradation via light-shielding effect or photosensitizers oxidative decomposition. The information obtained in this research would contribute to the understanding of photochemistry involving EPS, iron minerals, and steroid estrogens, providing new insights into their environmental behavior.
研究领域:
环境化学
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光化学
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环境科学
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微生物学
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地球化学
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产品关联
DOI
PubMed
高影响因子
Waste and Biomass Valorization
·
2023
·Vol. 15
·期 5
·2625-2635
·
IF 3.2
Luo Xiaoliang,Zhao Bincheng,Yao Junwen,Peng Mingguo,Mao Linqiang,Zhang Wenyi,Shen Rongyan
A large amount of estrogen is introduced into the feed to improve livestock growth, excessive residual estrogen would exist in the excrements. The accumulation of estrogen can cause the water and soil pollution around the farm, further inhibit growth and induce caner for organisms and human. Anaerobic digestion (AD) could effectively remove estrogen in livestock manure while the mechanism is still unclear. In this study, the mechanism of estrogen removal by AD was explored during AD process of pig manure. Estrone (E1), estradiol (E2) estriol (E3) and ethinylestradiol (EE2) were selected as research subjects. The removal rates of E1, E2, E3 and EE2 were 19.14, 28.62, 25.83 and 11.81%. Dissolved organic matters (DOM), especially humic acid, play an important role in reducing bioavailability of estrogen. Estrogen will be absorbed by DOM through structures such as aromatic ring and amides. Estrogen may also promote the growth of microorganisms which could degrade estrogen, such as Rhodococcus , Sphingomonas and Pseudomonas . The amount of these microorganisms and dissolved microbial metabolites did not change obviously. This study would give a new explanation for the removal of estrogen and can provide theoretical support for harmless treatment of pig manure. Graphical
研究领域:
环境科学
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微生物学
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生物技术
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生态毒理学
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废弃物管理
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DOI
高影响因子
PLACENTA
·
2024
·
IF 3
Gaoying Wang,Ruirui Dong,Haijian Zhao,Ningzhen Ye,Jing Wang,Jing Cheng,Xinrui Shi,Liang Luo,Ting Zhang
Background Abnormal bile acid metabolism leading to changes in placental function during pregnancy. To determine whether endoplasmic reticulum protein 29 (ERp29) can mediate the pregnancy effects of cholestasis by altering the level of trophoblast cell apoptosis. Methods ERp29 in serum of 66 intrahepatic cholestasis of pregnancy (ICP) pregnant women and 74 healthy were detected by ELISA. Subcutaneous injection of ethinyl estradiol (E2) was used to induce ICP in pregnant rats. Taurocholic acid (TCA) was used to simulate the ICP environment, and TGF-β1 was added to induce the epithelial mesenchymal transformation (EMT) process. The scratch, migration, and invasion test were used to detect the EMT process. ERp29 overexpression/knockdown vector were constructed and transfected to verify the role of ERp29 in the EMT process. Downstream gene was obtained through RNA-seq. Results Compared with the healthy pregnant women, the expression levels of ERp29 in serum of ICP pregnancy women were significantly increased (P < 0.001). ERp29 in the placenta tissue of the ICP pregnant rats increased significantly, and the level of apoptosis increased. The placental tissues of the ICP had high expression of E-cadherin and low expression of N-cadherin, snail1, vimentin. After HTR-8/SVneo cells were induced by TCA, EMT was inhibited, while the ERp29 increased. Cell and animal experiments showed that, knockdown of ERp29 reduced the inhibition of EMT, the ICP progress was alleviated. Overexpression of FOS salvaged the inhibitory effects of ERp29 on cell EMT. Discussion The high level of ERp29 in placental trophoblast cells reduced FOS mRNA levels, inhibited the EMT process and aggravated the occurrence and development of ICP.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
·
病理学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Wenhao Huang,Weiming Ai,Weiwei Lin,Fang Fang,Xuedong Wang,Haishan Huang,Randy A. Dahlgren,Huili Wang
Herein, eight common endocrine disrupting chemicals (EDCs) were exposed to zebrafish ( Danio rerio ) to investigate the relationship between different EDCs and their activated estrogen receptors. Under acute exposure, we identified five major malformation types whose incidence and deformity modes differed among EDCs. Luciferase analysis divided the EDC receptors into four categories: (i) triclosan (TCS), 17ß-estradiol (E2) and estriol (E3) mainly activated GPER expression; (ii) bisphenol A (BPA), p -(tert-octyl) phenol (POP), 17α-ethynylestradiol (EE2), E2 and E3 activated ERβ expression; (iii) E2 and E3 acted on both GPER and ERβ; and (iv) estrone (E1) and 9,9-bis(4-hydroxyphenyl)fluorene (BHPF) had little effect on the two receptors. In vivo immunofluorescence experiments on 96-hpf larvae provided evidence that TCS and POP acted on GPER and ERβ, respectively, while E2 acted on the two receptors simultaneously. Luciferase activities in the promoter regions of gper (−986 to −488) and erβ (−1998 to −1496) were higher than those in other regions, identifying these key regions as targets for transcription activity. TCS promoted GPER expression by acting on the JUND transcription factor, while POP promoted ERβ expression by activating the Foxl1 transcription factor. In contrast, E2 mainly regulated transcription of GPER and ERβ by Arid3a. These findings provide compelling evidence that different EDCs possess varying estrogen receptors, leading to differential regulatory pathways and abnormality symptoms. These results offer an experimental strategy and fundamental information to assess the molecular mechanisms of EDC-induced estrogen effects.
研究领域:
毒理学
·
环境科学
·
分子生物学
·
发育生物学
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DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2023
·
IF 9.5
Haojie Zeng,Feiyun Sun,Jianjun Zhang,Ying Wang,Songwen Yang,Dingyu Xing
Polyvinyl alcohol (PVA) has been employed and crosslinked as the selective layer of NF membranes with enhanced hydrophilicity. However, the influences of different crosslinking methods and agents on the reaction mechanism and membrane performance still need to be comprehensively studied. In this study, NF membranes were prepared by coating crosslinking (CC-membrane) and gradient crosslinking (GC-membrane) methods. Compared with CC-membrane, the GC-membrane possessed a 65% higher flux with Na 2 SO 4 rejection around 90%, under the optimal preparation conditions with PVA content of 0.10%, curing at 80 °C for 10 min. Crosslinking agents including 1,3,5-benzenetricarboxylic acid (TMA), 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) and pyromellitic dianhydride (PMDA) with different spatial structure were used to optimize the GC-membrane. As confirmed by SEM, XPS, FTIR and contact angle tests, the 6FDA-GC membrane showed a thinner, smoother and more hydrophilic selective layer, and kept an excellent balance between the water flux (88.6 L/m 2 h) and Na 2 SO 4 rejection (88.7%). This is because the 6FDA with a large molecule and flexible spatial structure could form a more integrated crosslinking structure compared to PMDA. Meanwhile, the 6FDA-GC membrane showed rejections of over 80% towards the endocrine-disrupting compound 17α-Ethinylestradiol and exhibited stable antifouling ability and durability. Overall, this work studied systematically the influences of various crosslinking agents on the GC-membrane, and verified the potential of hydrophilic PVA membranes for nanofiltration.
研究领域:
材料科学
·
化学工程
·
环境科学
·
膜技术
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Lijun Luo,Demei Meng,Lijin He,Xiaoxia Wang,Lihong Xia,Xuejun Pan,Fengzhi Jiang,Hongbin Wang,Jianhui Dai
A new porous C 3 N 4 /reduced graphene oxide/TiO 2 nanobelt catalyst (CRT) was assembled and used to remove 17α-ethinylestradiol (EE2) in the presence of peroxydisulfate (PS) and visible light. The characterization results showed that larger porous graphite carbon nitrides (pg-C 3 N 4 ) covered onto the surface of TiO 2 /reduced graphene oxide (RGO), in which layered RGO was wrapped onto the surface of anatase TiO 2 nanobelt uniformly. The layered RGO in CRT played significant role in separation of electron-hole pairs and nonradical activation. The electron paramagnetic resonance and quenching experiment revealed that h + , 1 O 2 and •O 2 – and direct electron transfer route contributed to complete removal of 6 mg/L EE2 within 6 min only with 0.5 g/L dosage and 1 mM PS. The degradation rate of EE2 in CRT/PS/Vis was 207.51 times than that in photocatalysis. The degradation products were identified by a solid phase extraction pretreatment method combined with ultra-high-performance liquid chromatography-mass spectrometry, and possible degradation pathways were proposed. Moreover, the estrogenic activities can be rapidly eliminated in CRT/PS/Vis process.
研究领域:
环境科学
·
材料科学
·
化学
·
水处理
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）