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Human HAND1 inhibits the conversion of cholesterol to Steroids in trophoblasts

Journal of Genetics and Genomics 2022年第4期49卷 350-363页

作者： Haibin Zhu Qianlei Ren Ziyi Yan Shouying Xu Jiahao Luo Ximei Wu Chao Tang National Clinical Research Center for Child Health of the Children’s Hospital Zhejiang University School of MedicineHangzhouZhejiang 310052China Department of Obstetrics and Gynaecology The First Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang 310003China Department of Pharmacology School of MedicineZhejiang UniversityHangzhouZhejiang 310058China

Steroidogenesis from cholesterol in placental trophoblasts is fundamentally involved in the establishment and maintenance of pregnancy.The transcription factor gene heart and neural crest derivatives expressed1(Hand1)promotes differentiation of mouse trophoblast giant cells.However,the role of HAND1 in human trophoblasts remains unknown.Here,we report that HAND1 inhibits human trophoblastic progesterone(P4)and estradiol(E2)from cholesterol through downregulation of the expression of steroidogenic enzymes,including aromatase,P450 cholesterol side-chain cleavage enzyme(P450 scc),and 3β-hydroxysteroid dehydrogenase type 1(3β-HSD1).Mechanically,although HAND1 inhibits transcription of aromatase by directly binding to aromatase gene promoter,it restrains transcription of P450 scc by upregulation of the methylation status of P450 scc gene promoter through its binding to ALKBH1,a demethylase.Unlike aromatase and P450 scc,HAND1 decreases 3β-HSD1 m RNA levels by the reduction of its RNA stability through binding to and subsequent destabilizing protein Hu R.Finally,HAND1 suppresses circulating P4 and E2 levels derived from JEG-3 xenograft and attenuates uterine response to P4 and E2.Thus,our results uncover a hitherto uncharacterized role of HAND1 in the regulation of cholesterol metabolism in human trophoblasts,which may help pinpoint the underlying mechanisms involved in supporting the development and physiological function of the human placenta.

关键词： HAND1 Trophoblast Cholesterol Steroids

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Breakthrough in the challenging P450-catalyzed chemoenzymatic synthesis of C14-functionalized Steroids

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中国科学:化学英文版 2023年第9期66卷 2435-2436页

作者： Manfred T.Reetz Frank Hollmann Max-Planck-Institut für Kohlenforschung Kaiser-Wilhelm-Platz 145480 MülheimGermany Tianjin Institute of Industrial Biotechnology Chinese Academy of SciencesTianjin 300308China Department of Biotechnology Delft Universityvan der Maasweg 92629 HZ DelftNetherlands

Intensive past research has demonstrated that cytochrome P450 monooxygenases are involved in the biosynthesis of numerous natural products and in human metabolism of various pharmaceuticals [1]. This inspired synthetic organic and pharmaceutical chemists to test them as catalysts in the oxidative hydroxylation of Steroids. Unfortunately, wildtype P450s generally proved to show low levels of regio-and diastereoselectivity as well as suboptimal activity.

关键词： Steroids catalyzed synthesis

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Four new Steroids from the marine soft coral-derived fungus Penicillium sp. SCSIO41201

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Chinese Journal of Natural Medicines 2020年第4期18卷 250-255页

作者： LONG Jie-Yi WANG Jun-Feng LIAO Sheng-Rong LIN Xiu-Ping ZHOU Xue-Feng LI Yun-Qiu YANG Bin LIU Yong-Hong CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica South China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China University of Chinese Academy of Sciences Beijing 100049China School of Pharmacy Guilin Medical UniversityGuilin 541004China South China Branch of Innovation Academy for Drug Discovery and Development Chinese Academy of SciencesGuangzhou 510650China

Penicildiones A-D(1-4), four new Steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy(5), stachybotrylactone B(6) and stachybotrin(7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 μmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 μmol·L-1.

关键词： Soft corals Marine fungus Penicillium sp. Steroids Penicildione

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A retrospective study of epidural and intravenous Steroids after percutaneous endoscopic lumbar discectomy for large lumbar disc herniation

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Chinese Journal of Traumatology 2017年第1期20卷 34-38页

作者： Yang Zhang Xin-Jian Yang Teng-Hui Zeng Yi-Yan Qiu Yi-Tian Wang Fei-Guo Liang Clinical School of Shenzhen Second People's Hospital Anhui Medical University. Hefei 230032. China Department of Spinal Surzery Shenzhen Second People's Hospital Shenzhen 518035 China

Objective: To assess the early curative effect of epidural or intravenous administration of Steroids during a percutaneous endoscopic lumbar discectomy (PELD). Methods: 28 consecutive patients who underwent PELD due to large lumbar disc herniation between November 2014 and January 2016 were followed up for 6 months. These patients were divided into two groups according to the treatment they received after PELD. 14 patients (Group A) were treated by PELD and epidural Steroids, while the other 14 patients (Group B) were treated by PELD and intravenous Steroids. We evaluated the effectiveness by the preoperative and postoperative visual analogue scale (VAS) scores for back and leg pain, and the postoperative Oswestry disability index (ODI) at 3 weeks after surgery via the clinical charts and telephone interview. Postoperative hospital stay and time return to work were investigated as well. Results: There is a significant decrease in VAS (back, leg), ODI, and time return to work ( p < 0.05). For VAS (back), Group A showed a significant decrease compared with Group B at 1 day and 1 week after surgery ( p = 0.011, p = 0.017). As for VAS (leg), Group A showed a significant decrease compared with Group B at 1 day, 1 week, 3 weeks, and 3 months follow-up examinations ( p = 0.002, p = 0.006, p < 0.001, p < 0.001). For ODI, Group A showed a notable decrease compared with Group B ( p < 0.001). The postoperative hospital stay in two groups was not statistically different ( p = 0.636). But the time return to work in Group A was significantly shorter than that in Group B ( p = 0.023). Conclusion: Patients who underwent PELD with epidural steroid administration for large lumbar disc herniation showed favorable curative effect compared with those who underwent PELD with intravenous steroid administration.

关键词： Large lumbar disc herniation Steroids Endoscopic lumbar discectomy

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Structural Modification for Antitumor Nitrogenous Steroids

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Chinese Journal of Structural Chemistry 2017年第12期36卷 2007-2019页

作者：谢田鹏杨康张立志陈德胜邹坤黄年玉 Hubei Key Laboratory of Natural Products Research and Development College of Biological and Pharmaceutical Sciences China Three Gorges University

Natural Steroids have been showing notable cytotoxic activities, which are quite interesting lead compounds for the development of anticancer drug including estramustine and prednimustine. Considering that these semi-synthetic molecules are nitrogen mustard functionalized steroidal derivatives, the present review is focused on the methodologies of introducing nitrogen atom or nitrogen-containing heterocycles on A^D rings or side chains of Steroids, and analysis of the structure-activity relationship（SAR） for these man-made cytotoxic Steroids.

关键词： Steroids structural modification N-hetercycles antitumor structure-activity relationship

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Apoptosis in Granulosa cells during follicular atresia: relationship with Steroids and insulin-like growth factors

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Cell Research 2004年第4期14卷 341-346页

作者： Yuan Song YU, Hong Shu SUI, Zheng Bin HAN, Wei LI, Ming Jiu LUO, Jing He TAN Laboratory of Animal Reproduction and Embryology College of Animal Sciences and Veterinary Medicine, Shandong Agricultural University, Taian, Shandong 271018, China Present address: College of life science. University of Beijing, Beijing, China. 1Laboratory of Animal Reproduction and Embryology College of Animal Sciences and Veterinary Medicine Shandong Agricultural University Taian Shandong 271018 China 1Laboratory of Animal Reproduction and Embryology College of Animal Sciences and Veterinary Medicine Shandong Agricultural University Taian Shandong 271018 China 1Laboratory of Animal Reproduction and Embryology College of Animal Sciences and Veterinary Medicine Shandong Agricultural University Taian Shandong 271018 China 1Laboratory of Animal Reproduction and Embryology College of Animal Sciences and Veterinary Medicine Shandong Agricultural University Taian Shandong 271018 China 1Laboratory of Animal Reproduction and Embryology College of Animal Sciences and Veterinary Medicine Shandong Agricultural University Taian Shandong 271018 China 1Laboratory of Animal Reproduction and Embryology College of Animal Sciences and Veterinary Medicine Shandong Agricultural University Taian Shandong 271018 China

It is well known that during mammalian ovarian follicular development, the majority of follicles undergo atresia at various stages of their development. However, the mechanisms controlling this selection process remain unknown. In this study, we investigated apoptosis in granulosa cells during goat follicular atresia by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The changes in the levels of Steroids, insulin-like growth factors (IGFs) and IGF receptors were studied by radioimmunoassay (RIA) and semi-quantitative reverse transcrip-tion-PCR. We found that the percentage of apoptotic granulosa cells in the atretic (A) follicles was significantly higher than that in the slightly atretic (SA) and healthy (H) follicles. The level of estradiol and the ratio of estradiol to progesterone in H follicles were significantly higher than those in A follicles. On the other hand, the level of progesterone was not significantly different among these follicle types. We also found that t

关键词： apoptosis ovarian follicle Steroids IGFs atresia.

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Anticancer activity of diterpenes and Steroids from Eunicella singularis against two- and three-dimensional breast cancer cell models

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Journal of Coastal Life Medicine 2017年第12期5卷 531-539页

作者： Sirine Lajili Monia Deghrigue Amal Abdelhamid Snezana Bjelogrlic Christian D.Muller Maria Valeria D’auria Abderrahman Bouraoui Laboratoire de Développement Chimique Galénique et Pharmacologique des Médicaments(LR12ES09).Unitéde Pharmacologie MarineFacultéde PharmacieUniversitéde Monastir5000 MonastirTunisia Institut Pluridisciplinaire Hubert Curien UMR 7178 CNRSFacultéde PharmacieUniversitéde Strasbourg74 Route du Rhin67401 IllkirchFrance National Cancer Research Center of Serbia Pasterova 1411000 BelgradeSerbia Department of Pharmacy University of Naples“Federico II”via D.Montesano 49I-80131 NapoliItaly.

Objective: To investigate the anticancer activity of two diterpenes [palmonine F (C1) and palmonine D (C2)] and three Steroids [cholesta-5,22-dien-3β-ol (C3), stigmasterol (C4) and 5α-cholest-5-en-3β-ol (C5)], isolated from the Mediterranean gorgonian Eunicella singularis, against MCF-7 breast cancer cell line. Methods: This study was performed on standard monolayer two-dimensional (2D) model to evaluate apoptosis by means of AnnexinV-FITC/PI flow cytometry and on three-dimensional (3D) spheroid model using Celigo imaging cytometer for spheroids size analysis. Results: Results indicated that both diterpenes and Steroids exhibited an important apoptotic activity in a concentration-dependent manner with EC50 values of 13, 49, 30, 66 and 65 μg/mL for C1, C2, C3, C4 and C5, respectively. Treatment of MCF-73D cell model with C1–C5 induced growth regression of spheroids in a concentration-dependent manner similar to the clinical anti-breast cancer drug Taxol;over ten days of incubation, growth rates were Steroids C3, C4 and C5, isolated from Eunicella singularis, might be used as anti-breast cancer candidate drugs for further development.

关键词： Eunicella singularis Diterpenes Steroids Apoptosis 3D tumor spheroid Flow cytometry

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Use of Steroids for facial nerve paralysis after parotidectomy:A systematic review

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World Journal of Clinical Cases 2015年第2期3卷 180-185页

作者： Kiran Varadharajan Issa Beegun Niall Daly Department of ENT St. George’s Hospital Department of ENT Royal National ThroatNose and Ear Hospital Department of ENT West Middlesex University Hospital

AIM: To systematically review the literature to assess the efficacy of corticoSteroids in treating postparotidectomy facial nerve palsy(FNP). METHODS: We searched the Cochrane library, EMBASE and MEDLINE(from inception to 2014) for studies assessing the use of corticoSteroids in post-parotidectomy FNP. Studies were assessed for inclusion and quality. Data was extracted from included studies. RESULTS: Two randomised controlled trials met the inclusion criteria. One study assessed the use of dexamethasone and the other prednisolone. None of the studies demonstrated a significant difference in the outcome of FNP post-parotidectomy with the use of corticoSteroids vs no therapy. The majority of FNP postparotidectomy is transient. Preoperative factors(size of tumour and malignancy), intraoperative factors(extent of parotidectomy and integrity of facial nerve at the end of the operation) are important in determining prognosis of FNP if it does occur.CONCLUSION: CorticoSteroids do not appear to improve FNP prognosis post-parotidectomy. Further studies assessing patients by cohort and with long term followup are required to increase scientific evidence.

关键词： Adrenal cortex hormones Facial paralysis Parotid diseases Steroids

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Sex Steroids and Breast Cancer: An Overview

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Journal of Cancer Therapy 2013年第4期4卷 851-856页

作者： Zeina Nahleh Juan E. Arenas Arafat Tfayli Department of Internal Medicine American University of Beirut Medical Center Beirut Lebanon. Department of Internal Medicine Division of Hematology-Oncology Paul L. Foster School of Medicine Texas Tech University Health Sciences Center El Paso USA Department of Internal Medicine Paul L. Foster School of Medicine Texas Tech University Health Sciences Center El Paso USA

Sex Steroids, also known as sex hormones are synthesized naturally by the gonads (ovaries or testes). The two main classes of sex Steroids, androgens and estrogens, are crucial hormones for the proper development and function of the body;they regulate sexual differentiation, the secondary sex characteristics, and sexual habits. They are also well known to influence many common cancers, especially hormonally driven cancers such as breast and prostate cancer. In this report, we review the association of sex Steroids with cancer and the potential use of endocrine manipulation in cancer therapy as well as the limitations and challenges faced in this field.

关键词： Sex Steroids Hormones Breast Cancer

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Simultaneous separation and identification of four Steroids by capillary HPLC-ESI-MS with column switch technology

Simultaneous separation and identification of four steroids ...

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西北地区第七届色谱学术报告会甘肃省第十二届色谱年会

作者： Yuming Dong Ningwei Lu Qiong an Ning Li School of Pharmacy Lanzhou University

A novel capillary-HPLC-ESI-MS method with column switch technology was established to separate and identify 18α-glycyrrhetinic acid,lupeol,pregnenolone and progesterone for the first time. The four Steroids could be separated with a C18 column and gradient elute within 30 min and detected by UV at 214 nm.Pregnenolone and progesterone interconvert in acid solution through adding hydrogen.They could not be separated and detected by UV at 214nm.However,they could be separated completely by ESI-MS when MS was used as capillary HPLC detector.The column switch column technology was used to preconcentrate the analytes.The peaks were sharp and symmetry. This method can be used to investigate these Steroids in biological samples,natural plant,fluids and food.

关键词： Steroids capillary HPLC-ESI-MS column switch

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