INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Yanan Zhang,Xue Li,Di Xu,Mengyun Wu,Yinghui Dai,Mingyu Xia,Dong Wang
Bufadienolides are the main active ingredients of Venenum Bufonis, which is a widely used traditional Chinese medicine secreted from parotoid gland and skin glands of Bufo bufo gargarizans . According to the transcriptome analysis, “cholesterol-bile acid-bufadienolidies pathway” was proposed as animal-derived bufadienolides biosynthesis pathway by us previously. In this pathway 3 β -hydroxysteroid dehydrogenase (3 β HSD) and steroid 5 β -reductase (SRD5 β ) might be the key enzymes to convert the A/B ring to cis -configuration. Therefore, as the second report of our group, here we report the cloning of the full length of SRD5 β cDNA of B. bufo gargarizans ( Bbg - SRD5β ) from the parotoid gland of B. bufo gargarizans for the first time, and site-directed mutagenesis was used to explored the character of Bbg -SRD5 β . Bbg -SRD5 β had an open reading frame of 981 bp and encoded 326 amino acids residues. The expression conditions of the recombinant Bbg -SRD5 β in E. coli BL21 (DE3) harbored with pCold- Bbg -SRD5 β was optimized as induction for 10 h at 15 °C with 0.1 mM IPTG. With NADPH as a cofactor, Bbg -SRD5 β can reduce the Δ 4,5 double bonds of progesterone to generate dihydroprogesterone õwithout substrate inhibition effect. The catalytic rate of mutant type Bbg -SRD5 β -Y132G was 1.8 times higher than that of wild type Bbg -SRD5 β . Although Bbg -SRD5 β was almost unable to reduce the progesterone to dihydroprogesterone after mutation of V309, the affinity of enzyme with NADPH changed significantly. Bbg -SRD5 β is the key enzymes to convert the A/B ring of steroid to cis -configuration, and V309 is a key site affecting the binding affinity of enzyme with NADPH, and the mutation of Y132 can adjust the catalytic rate of Bbg -SRD5 β .
研究领域:
生物化学
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分子生物学
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中医药学
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药理学
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DOI
PubMed
高影响因子
Synthetic and Systems Biotechnology
·
2025
·
IF 4.4
Ying Wang,Ruosi Zhang,Mingdong Yao,Wenhai Xiao,Ying Wang,Ying-Jin Yuan
Progesterone is a widely used therapeutic hormone and a common precursor for the synthesis of pharmaceutical steroids in both mammals and plants. It has been successfully produced in heterologous microorganisms, but the market demand has not been met. The low progesterone yield, possibly due to product stress, may put pressure on the growth of strains and limit product synthesis efficiency. In this study, key pathways and genes that cause changes in amino acid and lipid metabolism and protein transport were identified through omics analysis. The expression of transporters leads to increased progesterone production and alleviated growth inhibition. Two related genes (gene IDs: 2912325 and 2908366) encoding the transporters glpF and SNQ2 improved production by 29.2% and 51.7%, respectively. Isoenzymes of native and exogenous transporters were screened and overexpressed. YCF1 from Saccharomyces cerevisiae exhibited the greatest benefit, increasing progesterone synthesis by 69.6%. Our findings help reveal the impact of product stress on cellular metabolism and processes, providing research directions and literature support for the synthesis of other products.
研究领域:
生物化学
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合成生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2022
·Vol. 119
·期 15
·e2117004119
·
IF 12.779
Wentao An,Hui Lin,Lijuan Ma,Chao Zhang,Yuan Zheng,Qiuxia Cheng,Chuanshun Ma,Xiang Wu,Zihao Zhang,Yani Zhong,Menghui Wang,Dongfang He,Zhao Yang,Lutao Du,Shiqing Feng,Chuanxin Wang,Fan Yang,Peng Xiao,Pengju Zhang,Xiao Yu,Jin-Peng Sun
GPR126 is a member of the adhesion G protein-coupled receptors (aGPCRs) that is essential for the normal development of diverse tissues, and its mutations are implicated in various pathological processes. Here, through screening 34 steroid hormones and their derivatives for cAMP production, we found that progesterone (P4) and 17-hydroxyprogesterone (17OHP) could specifically activate GPR126 and trigger its downstream Gi signaling by binding to the ligand pocket in the seven-transmembrane domain of the C-terminal fragment of GPR126. A detailed mutagenesis screening according to a computational simulated structure model indicated that K1001ECL2 and F1012ECL2 are key residues that specifically recognize 17OHP but not progesterone. Finally, functional analysis revealed that progesterone-triggered GPR126 activation promoted cell growth in vitro and tumorigenesis in vivo, which involved Gi-SRC pathways in a triple-negative breast cancer model. Collectively, our work identified a membrane receptor for progesterone/17OHP and delineated the mechanisms by which GPR126 participated in potential tumor progression in triple-negative breast cancer, which will enrich our understanding of the functions and working mechanisms of both the aGPCR member GPR126 and the steroid hormone progesterone.
研究领域:
癌症生物学
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分子生物学
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细胞信号传导
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药理学
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产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2021
·
IF 6.707
Minghui Zan,Shuai An,Lei Cao,Yulu Liu,Li Li,Mingfeng Ge,Pai Liu,Zaihui Wu,Wen-Fei Dong,Qian Mei
Progesterone (P4) is an important steroid hormone that act as an indicator in the female reproductive processes; thus, following its concentration levels in human serum is important for diagnosis of early pregnancy. In this work, carbon dots (CDs) were designed via a dry-heating method, and the novel CDs exhibited good dispersion stability and excellent photostability. Under optimal conditions, the as-prepared CDs displayed high selectivity and sensitivity for P4 and exhibited a fast-responsive (within 1 min) fluorescence intensity enhancement signal in aqueous solution. For further application, the fluorescence sensing system was further extended to monitoring progesterone in real samples with acceptable recoveries. The methodology developed here offers a promising direction for the detection of clinical biomarkers that are closely related to human health.
研究领域:
分析化学
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生物医学
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产品关联
DOI
高影响因子
Environmental Science-Processes & Impacts
·
2021
·Vol. 23
·期 10
·1566-1577
·
IF 4.238
Cécilia Siri,Yang Liu,Thibault Masset,William Dudefoi,Dean Oldham,Matteo Minghetti,Dominique Grandjean,Florian Breider
The sorption of hydrophobic organic compounds (HOC) onto microplastics is relatively well reported in the literature, while their desorption remains poorly investigated, especially in biological fluids. The present study investigated the sorption and desorption of progesterone on polyethylene (PE), polypropylene (PP), and polystyrene (PS) microplastics. The sorption experiments showed that the equilibrium was reached in a few hours for all plastics. A sorption efficiency of 357.1 μg g−1 was found for PE and PS, and 322.6 μg g−1 for PP. Sorption experiments indicated that adsorption would certainly happen via surface sorption and a potentially pore-filling mechanism. The desorption was carried out in Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF), whose formulations were more complex than similar models reported so far. It has been found that the desorption was higher in SIF as compared to SGF, due to micelle formation in SIF promoting the pollutant solubilization. The sorption of pepsin onto microplastics has also been revealed, suggesting a competition between pollutants and pepsin for sorption sites and a potent reduction in pollutant solubilization. This study indicates that the ingestion of microplastics could be considered as an additional route of exposure to pollutants and therefore emphasizes pollutant bioavailability for aquatic organisms.
研究领域:
环境科学
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毒理学
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生物医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2025
·
IF 4.3
Hui-Na Luo,Hong-Yuan Yang,Zai-Mei Wang,Jia-Mei Luo,Tong-Tong Zhang,Zeng-Ming Yang
Progesterone (P4) is essential for pregnancy establishment and maintenance. Clinically, P4 is widely used to regulate the menstrual cycle, maintain pregnancy, and treat luteal phase deficiency. However, P4 administration protocols, particularly regarding routes, dosage, and timing remain poorly defined. Although excessive P4 impairs embryo implantation and decidualization in mice, the underlying mechanism remains unclear. Our data show that decidualization in day 8 pregnant mice and artificial decidualization in day 8 pseudopregnant mice are impaired by 4 mg or 8 mg/mouse P4. The mRNA levels of Prl8a2 and Prl3c1, markers of in vitro decidualization are significantly downregulated by 10 or 20 μM P4. The uterine fluorescent signal of indoleamine 2,3-dioxygenase 1 (IDO1) and protein levels of tryptophan 2,3-dioxygenase (TDO) are increased after ovariectomized mice are treated with excessive P4. Treatment of uterine stromal cells with excessive P4 also significantly upregulates the protein levels of IDO1 and TDO, and kynurenine (Kyn) secretion. Epacadostat (IDO1 antagonist) or RU486 (progesterone receptor antagonist) effectively block P4-induced Kyn elevation. The mRNA levels of Prl8a2 and Prl3c1 and the protein levels of BMP2 are significantly inhibited by Kyn. The high-dose of P4 activates the aryl hydrocarbon receptor (AhR) and its downstream targets CYP1A1 and CYP1B1. Under in vitro decidualization, the mRNA levels of Prl8a2 and Prl3c1 are inhibited by 2-OH-E2 and 4-OH-E2, the catalytic products of CYP1A1 and CYP1B1, respectively. CH-223191, a specific AhR antagonist, effectively counteracts the effects of Kyn on Cyp1a1, Cyp1b1, and Prl8a2 expression. Additionally, nucleolar size in stromal cells is increased both in vivo and in vitro following excessive P4 treatment. Our findings suggest that excessive P4 impairs mouse decidualization via the Kyn-AhR pathway.
研究领域:
生殖生物学
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分子内分泌学
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妇产科学
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胚胎植入
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信号转导
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产品关联
DOI
PubMed
高影响因子
Frontiers of Environmental Science & Engineering
·
2022
·Vol. 16
·期 10
·1-12
·
IF 6.048
Liang Jinhui,Luo Yuchen,Li Benhang,Liu Shiqi,Yang Liansheng,Gao Peng,Feng Li,Liu Yongze,Du Ziwen,Zhang Liqiu
Progesterones are ubiquitous in hospital wastewater (HWW) with concentrations much higher than those of estrogens and androgens. To ensure that these water systems are safe to use, disinfection is crucial during HWW treatment by providing “front line” defense against biological contaminations. Here, five disinfection processes, namely, chlorine (Cl 2 ), chlorine dioxide (ClO 2 ), ozone (O 3 ), ultraviolet (UV)), and UV/chlorine (UV/Cl 2 ), were selected to investigate their removal efficiencies for progesterones in primary filtration and secondary biological treatment effluents. There were 61 natural and synthetic progesterones detected in HWW, with the natural progesterones being the main components with a concentration of 845.51 ng/L and contributing to 75.08% of the total progesterones. The primary filtration treatment presented insignificant removal effects on the progesterones, while the secondary biological treatment significantly reduced the progesterone content by biodegradation. The order of removal efficiencies of total progesterones by different disinfection processes was UV/Cl 2 > Cl 2 > O 3 > ClO 2 > UV. UV/Cl 2 showed the highest removal efficiency against progesterones mainly due to the activation of Cl 2 by ultraviolet (UV) photolysis, which helps open the heterocyclic, aromatic, and phenolic rings, thus accelerating progesterone degradation. In addition, the removal efficiencies of natural progesterones in the five disinfection processes were higher than those of synthetic progesterones (progesterone derivatives, 19-nortestosterone derivatives, and 17α-hydroxyprogesterone derivatives).
研究领域:
环境科学
·
医学
·
生物学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Zhuofan Huang,Qintie Lin,Haoyu Luo,Pengran Guo,Qingsong Weng,Yongqian Lei,Shuailong Cheng,Shuang-Shuang Liu
Progesterone (PGT), a widely used progestogen, has become a refractory pollutant present in urban runoff. The removal of PGT in wastewater is urgent owing to its endocrine disruption. In this study, a nano-CuO loaded halloysite nanotube (CuO/HNTs) was prepared by a simple hydrothermal method, which could be used as a catalyst to activate persulfate (PS) for the degradation of PGT. The characterizations showed that the nano-CuO was uniformly loaded on the HNTs to form corn-like structures with a large specific surface area. The optimal PGT degradation efficiency (100%) was achieved with the addition of 0.5 g/L catalyst and 7 mM PS. The effects of pH, HCO 3 – and Cl - on the catalytic activity of the CuO/HNTs-PS system were investigated. The results showed that 1) pH had little effect due to the buffer effect of Al 2 O 3 in HNTs, and nearly neutral solutions were obtained after reaction even in strong acidic or alkaline conditions, 2) low concentrations of HCO 3 – and Cl - had almost no impact on PGT degradation. Furthermore, the degradation mechanism was explored by quenching reactions, XPS, EPR studies and electrochemical experiments. The results demonstrated that the reaction was divided into the free radical pathway (SO 4 •- and •OH generation by the mutual transformation of PS, Cu(I), Cu(II), and Cu(III)) and the nonradical pathway (electron transfer process from the organic pollutant to the CuO/HNTs). In addition, the byproducts of PGT in the process were determined by LC-MS, and the possible transformation pathways were proposed. The CuO/HNTs-PS system might provide some new insights for the remediation of wastewaters.
研究领域:
环境科学
·
生物学
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产品关联
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2020
·
IF 4.089
Chunyang Guo,Qi Zhang,Bingqing Zhu,Zaiyong Zhang,Xiaoyu Ma,Wenjuan Dai,Xiaoyi Gong,Guobin Ren,Xuefeng Mei
Progesterone (Prog), a natural steroid hormone, is widely used in birth control pills and menopausal hormone replacement therapies. Phloroglucinol (SPF) and resveratrol (RSV) are also two kinds of active products that can be used during pregnancy. Drug–drug cocrystals of Prog with SPF and RSV were designed and successfully synthesized for purpose of bringing improvements of drug properties, including solubility, hydroscopic stability, and color stability. The cocrystals and their hydrate structures were systematically characterized by X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. In addition, powder dissolution experiments of Prog, Prog-SPF, and Prog-RSV were conducted in aqueous solutions with the presence of different surfactants, and the result revealed that the Prog-SPF cocrystal exhibits a superior solubility compared with Prog and Prog-RSV. Furthermore, the Prog-SPF cocrystal also enhances the hydroscopic stability and color stability of SPF. Those findings may provide a promising formulation to overcome some weaknesses of the parent drugs.
研究领域:
药学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
iScience
·
2023
·
IF 5.8
Yating Xie,Wenya Guo,Xi Shen,Weina Yu,Yanping Kuang,Qiuju Chen,Hui Long,Qifeng Lyu,Li Wang
Summary Progestin-primed ovarian stimulation (PPOS) is a new ovulation stimulation protocol, and its role in ovulation and regulatory mechanism is unclear. The clinical PPOS protocol was simulated in mice. The ovulated oocytes, estradiol, progesterone, and luteinizing hormone (LH) levels were analyzed at different hours after trigger. mRNA extraction and real-time PCR, hematoxylin and eosin staining, and immunofluorescence of ovaries were used to explore the involved signaling pathways. The PPOS group had a delayed ovulation at 12.5 h after trigger. Its suppressed LH level reduced the expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) on the preovulatory follicles before trigger and significantly decreased the following progesterone synthesis, blood progesterone level, and progesterone receptor (PGR) expression within 4–6 h after trigger. Furthermore, the important ovulatory genes regulated by PGR including ADAMTS-1, VEGF-A, and EDN2 were downregulated, ultimately delaying the ovulation. PPOS suppresses the LH level before trigger and decreases the synthesis of progesterone after trigger, thus delaying the ovulation by downregulating the LHCGR-PGR pathway.
研究领域:
生殖生物学
·
内分泌学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2014
·Vol. 39
·期 1
·555-565
·
IF 3.159
Li-Yun Wang,Ling-Yu Dong,Luan Chen,Ya-Bing Fan,Jing Wu,Xiang-Feng Wang,Meng-Xia Xie
A novel water-soluble beta-cyclodextrin (β-CD)-functionalized ZnS quantum dot (QD)–neutral red (NR) fluorescence resonance energy transfer (FRET) probe for the selective determination of the concentration of megestrol acetate in river water has been developed. The water-soluble and low-toxicity β-CD-functionalized ZnS QDs were first synthesized, and their characterization was confirmed by transmission electron microscopy and infrared, UV-vis and fluorescence emission spectra. The NR molecule can enter the cavity of the β-CD anchored onto the surfaces of the ZnS QDs in its neutral form, forming the FRET probe. Compared with other steroid hormones, the probe can selectively recognize megestrol acetate at a lower concentration level. The possible underlying mechanism of the probe with nine steroid hormones was discussed in detail. The fluorescence quenching fractions of the probe presented a satisfactory linearity with the concentrations of megestrol acetate, and its limit of detection was calculated to be 0.0083 μM. Coupled with sample pretreatment procedures, the probe has been applied to the determination of megestrol acetate in river water. The average recoveries of megestrol acetate in the spiking levels of 0.001 μM–10 μM ranged from 97% to 110% with a relative standard deviation below 15%, which was similar to those for HPLC or MS techniques.
研究领域:
分析化学
·
环境科学
·
药物分析
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产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2024
·
IF 3.8
He Ziyun,Dai Haibing,Shen Jian,Huang Yanjie,Liu Jinsong,Yan Renqing,Zhang Feng,Yan Shengkai
17α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is challenging due to its low physiological concentration. The high false-positive rates of immunoassays necessitate the development of more accurate methods. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers increased specificity and sensitivity, yet standardized procedures for 17α-OHP measurement are required for clinical application. A candidate reference measurement procedure (cRMP) using isotope dilution LC-MS/MS was developed for 17α-OHP quantification in DBS. By utilizing stable isotope-labeled D8-17α-OHP as an internal standard, the cRMP was optimized, covering sample preparation, calibration, and LC-MS/MS analysis. The method performance was validated across several parameters, including precision, accuracy, specificity, detection limits, and matrix effects. Clinical applicability was further assessed through the establishment of reference intervals for healthy newborns. The developed cRMP exhibited a linear range of 1.00 to 80.00 ng/mL for 17α-OHP, with detection and quantification limits of 0.14 ng/mL and 0.52 ng/mL, respectively. Inter- and intraday precision demonstrated coefficients of variation within 1.27 to 5.69%. The recovery rates and matrix effects were well within acceptable limits, ensuring method reliability. Clinical application showed distinct reference intervals for healthy newborns that were unaffected by sex but influenced by weight and gestational age. This method significantly enhances CAH diagnostic accuracy in newborns, providing a valuable tool for clinical laboratories and improving newborn screening program standardization and traceability.
研究领域:
医学检验
·
临床化学
✓ 已验证
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）