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Frontiers in Cell and Developmental... 2021Hexestrol (HES) is a synthetic non-steroidal estrogen that was widely used illegally to boost the growth rate in livestock production and aquaculture. HES can also be...
Hexestrol (HES) is a synthetic non-steroidal estrogen that was widely used illegally to boost the growth rate in livestock production and aquaculture. HES can also be transferred to humans from treated animals and the environment. HES has been shown to have an adverse effect on ovarian function and oogenesis, but the potential mechanism has not been clearly defined. To understand the potential mechanisms regarding how HES affect female ovarian function, we assessed oocyte quality by examining the critical events during oocyte maturation. We found that HES has an adverse effect on oocyte quality, indicated by the decreased capacity of oocyte maturation and early embryo development competency. Specifically, HES-exposed oocytes exhibited aberrant microtubule nucleation and spindle assembly, resulting in meiotic arrest. In addition, HES exposure disrupted mitochondrial distribution and the balance of mitochondrial fission and fusion, leading to aberrant mitochondrial membrane potential and accumulation of reactive oxygen species. Lastly, we found that HES exposure can increase cytosolic Ca levels and induce DNA damage and early apoptosis. In summary, these results demonstrate that mitochondrial dysfunction and perturbation of normal mitochondrial fission and fusion dynamics could be major causes of reduced oocyte quality after HES exposure.
PubMed: 34295902
DOI: 10.3389/fcell.2021.708980 -
Asian Pacific Journal of Cancer... 2015Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. The sequence similarities of human ERα, mouse ERα, rat ERα, dog... (Review)
Review
Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. The sequence similarities of human ERα, mouse ERα, rat ERα, dog ERα, and cat ERα are above 90%, but structures of ERα may different among species. Estrogen can be agonist and antagonist depending on its target organs. This hormone play roles in several diseases including breast cancer. There are variety of the relative binding affinity (RBA) of ER and estrogen species in comparison to 17β-estradiol (E2), which is a natural ligand of both ERα and ERβ. The RBA of the estrogen species are as following: diethyl stilbestrol (DES)>hexestrol>dienestrol>17β-estradiol (E2)>17-estradiol>moxestrol>estriol (E3)>4-OH estradiol>estrone-3-sulfate. Estrogen mimetic drugs, selective estrogen receptor modulators (SERMs), have been used as hormonal therapy for ER positive breast cancer and postmenopausal osteoporosis. In the postgenomic era, in silico models have become effective tools for modern drug discovery. These provide three dimensional structures of many transmembrane receptors and enzymes, which are important targets of de novo drug development. The estimated inhibition constants (Ki) from computational model have been used as a screening procedure before in vitro and in vivo studies.
Topics: Animals; Cats; Dogs; Estrogen Receptor alpha; Humans; Ligands; Mice; Protein Conformation; Rats; Selective Estrogen Receptor Modulators
PubMed: 25824732
DOI: 10.7314/apjcp.2015.16.6.2161 -
International Journal of Medical... Mar 2023There has been an explosion in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) because of the indiscriminate use of antibiotics. In this study, we...
There has been an explosion in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) because of the indiscriminate use of antibiotics. In this study, we repurposed hexestrol (HXS) as an antibacterial agent to fight planktonic and biofilm-related MRSA infections. HXS is a nonsteroidal synthetic estrogen that targets estrogen receptors (ERα and ERβ) and has been used as a hormonal antineoplastic agent. In our work, the minimum inhibitory concentrations (MICs) were determined using the antimicrobial susceptibility of MSSA and MRSA strains. Anti-biofilm activity was evaluated using biofilm inhibition and eradication assays. Biofilm-related genes were analyzed with or without HXS treatment using RTqPCR analysis of S. aureus. HXS was tested using the checkerboard dilution assay to identify antibiotics that may have synergistic effects. Measurement of ATP and detection of ATPase allowed the determination of bacterial energy metabolism. As shown in the results, HXS showed effective antimicrobial activity against S. aureus, including both type strains and clinical isolations, with MICs of 16 µg/mL. Sub-HXS strongly inhibited the adhesion of S. aureus. The content of extracellular polymeric substances (EPS) and the relative transcription levels of eno, sacC, clfA, pls and fnbpB were reduced after HXS treatment. HXS showed antibacterial effects against S. aureus and synergistic activity with aminoglycosides by directly interfering with cellular energy metabolism. HXS inhibits adhesion and biofilm formation and eradicates biofilms formed by MRSA by reducing the expression of related genes. Furthermore, HXS increases the susceptibility of aminoglycosides against MRSA. In conclusion, HXS is a repurposed drug that may be a promising therapeutic option for MRSA infection.
Topics: Methicillin-Resistant Staphylococcus aureus; Hexestrol; Staphylococcus aureus; Drug Repositioning; Anti-Bacterial Agents; Aminoglycosides; Biofilms; Microbial Sensitivity Tests
PubMed: 37001448
DOI: 10.1016/j.ijmm.2023.151578 -
Journal of Cellular and Molecular... Feb 2022Despite the growing recognition of ITGB3BP as an essential feature of various cancers, the relationship between ITGB3BP and glioma remains unclear. The main aim of this...
Despite the growing recognition of ITGB3BP as an essential feature of various cancers, the relationship between ITGB3BP and glioma remains unclear. The main aim of this study was to determine the prognostic and diagnostic value of ITGB3BP in glioma. RNA-Seq and microarray data from 2222 glioma patients were included, and we found that the expression level of ITGB3BP in glioma tissues was significantly higher than that in normal brain tissues. Moreover, ITGB3BP can be considered an independent risk factor for poor prognosis and has great predictive value for the prognosis of glioma. Gene Set Enrichment Analysis results showed that ITGB3BP contributes to the poor prognosis of glioma by activating tumour-related signalling pathways. Some small-molecule drugs were identified, such as hexestrol, which may specifically inhibit ITGB3BP and be useful in the treatment of glioma. The TIMER database analysis results revealed a correlation between the expression of ITGB3BP and the infiltration of various immune cells in glioma. Our findings provide the first evidence that the up-regulation of ITGB3BP correlates with poor prognosis in human glioma. Thus, ITGB3BP is a potential new biomarker that can be used for the clinical diagnosis and treatment of glioma.
Topics: Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Nuclear Proteins; Signal Transduction; Up-Regulation
PubMed: 34953037
DOI: 10.1111/jcmm.17127 -
Frontiers in Oncology 2022Parathyroid carcinoma (PC) is an extremely rare malignant tumor with an incidence of about 6 new cases per 10 million inhabitants per year. While several papers have...
BACKGROUND
Parathyroid carcinoma (PC) is an extremely rare malignant tumor with an incidence of about 6 new cases per 10 million inhabitants per year. While several papers have been published on treatments and outcomes of PC patients with loco-regional disease, little is known about the prognosis, treatment strategies, and prognostic factors of patients with distant metastasis.
MATERIALS AND METHODS
We performed a systematic review and a pooled analysis of histopathologically confirmed PC cases published in literature using the following keywords: "metastasis-metastatic-secondary nodes" AND "parathyroid carcinoma". Original case reports and case series reporting metastatic parathyroid carcinoma were included. Data from 58 articles were extracted in a piloted form by five reviewers on a shared database.
RESULTS
Seventy-nine patients with metastatic PC were identified between 1898 and 2018. Ten (13%) patients had synchronous metastases, while metachronous metastases occurred in 43 (54%) patients. The remaining 26 patients developed metastatic disease concomitantly to local recurrence. Primary hyperparathyroidism guided the diagnosis of metastatic recurrence in 58 (73%) patients. Surgery was the main primary approach adopted, as it was performed in 43 (54%) patients. Twenty (25%) patients underwent systemic antineoplastic therapy, consisting of chemotherapy, immunotherapy, tyrosine kinase inhibitors, and hexestrol therapy. Bone resorption inhibitors had a limited efficacy in the long-term control of hypercalcemia. After a median follow-up of 37.5 months, 43 (55%) patients died, 22 (51%) due to the consequences of uncontrolled PHPT. The median overall survival was 36 months (range: 1-252). Surgery was associated with a better OS (HR 0.48, 95% CI 0.26-0.88), whereas bone metastases represented a negative prognostic factor (HR 2.7, 95% CI 1.4-5.2).
CONCLUSION
Metastatic PC has a relatively poor prognosis. The main goals of treatment are to counteract tumor growth and control hypercalcemia. Surgery of metastases is the best approach to achieve rapid control of PHPT and longer survival. Target therapies and immunotherapy deserve to be extensively tested in metastatic PC and strategies to better control hypercalcemia should be implemented.
PubMed: 36226055
DOI: 10.3389/fonc.2022.997009 -
International Journal of Molecular... Feb 2019The rapid analysis of stilbene estrogens is crucially important in the environment, food and health sectors, but quantitation of lower detection limit for stilbene...
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 (IC) 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.
Topics: Animals; Binding, Competitive; Diethylstilbestrol; Dose-Response Relationship, Drug; Estrogen Receptor alpha; Hydrogen Bonding; Inhibitory Concentration 50; Kinetics; Ligands; Milk; Models, Molecular; Molecular Conformation; Protein Binding
PubMed: 30744198
DOI: 10.3390/ijms20030744 -
Environmental Science and Pollution... Jul 2022Over recent decades, steroidal estrogens have become an emerging and very serious issue as they pose a serious threat to living organisms, soil, plants, and water...
A sensitive, robust method for determining natural and synthetic hormones in surface and wastewaters by continuous solid-phase extraction-gas chromatography-mass spectrometry.
Over recent decades, steroidal estrogens have become an emerging and very serious issue as they pose a serious threat to living organisms, soil, plants, and water resources in general. Estrogens have therefore been the subject of considerable scientific attention in order to develop new methodologies for its determination, being able of detecting them at very low concentrations. Those procedures minimize or eliminate the consumption of organic solvents and reagents that may be incompatible with the environment. In this respect, we developed a sensitive, selective method for the simultaneous determination of thirteen natural and synthetic hormones present at the nanogram-per-liter level in various types of water by using continuous solid-phase extraction in combination with gas chromatography and mass spectrometry (GC-MS). The target analytes were preferentially sorbed on an Oasis HLB sorbent column (80 mg) and eluted with acetone (600 µL) for derivatization with a mixture of 70 µL of N,O-bis(trimethylsilyl) trifluoroacetamide and trimethylchlorosilane and 35 µL of petroleum ether in a household microwave oven at 200 W for 4 min. Under optimum conditions, the ensuing method exhibited good linearity (r ≥ 0.998), good precision (RSD ≤ 7%), high recoveries (92-103%), and low detection limits (0.01-0.3 ng L). The method outperforms existing alternatives in robustness, sensitivity, throughput, flexibility-it allows both estrogens, progestogens, and androgens to be determined simultaneously-and compliance with the principles of Green Chemistry. It was successfully used to analyze various types of water samples (mineral, tap, well, pond, swimming pool, river, and waste) that were found to contain four estrogens (estrone, 17β-estradiol, 17α-ethinylestradiol, and hexestrol), two progestogens (testosterone, dihydrotestosterone), and one progestogen (progesterone) at concentrations ranging from 3.0 to 110 ng L.
Topics: Estrogens; Ethinyl Estradiol; Gas Chromatography-Mass Spectrometry; Progestins; Solid Phase Extraction; Wastewater; Water; Water Pollutants, Chemical
PubMed: 35290579
DOI: 10.1007/s11356-022-19577-1 -
Food Chemistry: X Jun 2022A simple and rapid method based on miniaturized solid-phase microextraction (mini-SPME) followed by gas chromatography-mass spectrometry was developed to identify eight...
A simple and rapid method based on miniaturized solid-phase microextraction (mini-SPME) followed by gas chromatography-mass spectrometry was developed to identify eight endocrine disruptors (atrazine, diethylstilbestrol, hexestrol, estrone, estradiol, ethinylestradiol, norgestrel, and megestrel) in drinking water samples. Extraction parameters was optimized and further analyses was performed using them. The optimum temperature for the determination of endocrine disruptors in water was 80 °C; the optimum extraction and preincubation times were 60 and 20 min, respectively. The studied linear range of endocrine disruptors was 10.0-1000 μg mL. The limit of detection ranged from 0.020 to 0.087 μg mL. The correlation coefficient (r) was 0.96-0.99. This research introduces a novel method for detecting analytes at extremely low concentrations, as well as the possibility of combining several detection technologies to give high-accuracy qualitative and quantitative determination of endocrine disruptors in aqueous samples.
PubMed: 35663598
DOI: 10.1016/j.fochx.2022.100345 -
RSC Advances Feb 2020Using a sandwich-type immunoassay, a novel electrochemical immunosensor based on the successful preparation of a hexestrol (HEX) monoclonal antibody was successfully...
Using a sandwich-type immunoassay, a novel electrochemical immunosensor based on the successful preparation of a hexestrol (HEX) monoclonal antibody was successfully constructed to detect four phenolic oestrogens: HEX, diethylstilboestrol (DES), dienestrol (DE) and bisphenol A (BPA). An innovative strategy to design the HEX monoclonal antibody/mercapto acetic acid (MACA)/nanogold immunosensor was developed by combining a nanosized effect, self-assembly and specific immune technology. The differential pulse voltammetry (DPV) response for four phenolic oestrogens was in the order BPA > DE > HEX > DES with detection limits of 0.037, 0.047, 0.052 and 0.060 ng mL, respectively (S/N = 3). This immunosensor exhibits superior electrochemical properties with a wide linear range, low detection limit, excellent reproducibility and high selectivity. Compared with a high-performance liquid chromatography method, a high accuracy of DES detection in beef, duck and milk powder samples was achieved by the immunosensor proposed, which exhibits great potential for the detection of phenolic oestrogens in applications in environmental and food safety.
PubMed: 35496517
DOI: 10.1039/d0ra00006j -
ACS Omega Sep 2020Of the numerous infectious diseases afflicting humans, anthrax disease, caused by , poses a major threat in its virulence and lack of effective treatment. The currently...
Of the numerous infectious diseases afflicting humans, anthrax disease, caused by , poses a major threat in its virulence and lack of effective treatment. The currently lacking standards of care, as well as the lengthy drug approval process, demonstrate the pressing demand for treatment for infections. The present study screened 1586 clinically approved drugs in an attempt to identify repurposable compounds against , a relative strain that shares many physical and genetic characteristics with . Our study yielded five drugs that successfully inhibited growth: dichlorophen, oxiconazole, suloctidil, bithionol, and hexestrol. These drugs exhibited varying levels of efficacy in broad-spectrum experiments against several Gram-positive and Gram-negative bacterial strains, with hexestrol showing the greatest inhibition across all tested strains. Through tests for the efficacy of each drug on , bithionol was the single most potent compound on both solid and liquid media and exhibited even greater eradication of in combination with suloctidil on solid agar. This multifaceted study of approved drugs demonstrates the potential to repurpose these drugs as treatments for anthrax disease in a time-efficient manner to address a global health need.
PubMed: 32905429
DOI: 10.1021/acsomega.0c03207