Article
Chemistry, Multidisciplinary
Xin Chai, Xue-ping Hu, Xin-yue Wang, Hua-ting Wang, Jin-ping Pang, Wen-fang Zhou, Jia-ning Liao, Lu-hu Shan, Xiao-hong Xu, Lei Xu, Hong-guang Xia, Ting-jun Hou, Dan Li
Summary: This study discovered an AR-GR dual binder H18 and identified the AR-GR dual antagonist HD57 with antagonistic activity towards both AR and GR. It provides an efficient and rational strategy for discovering novel AR-GR dual antagonists and important clues for developing new therapeutics for castration-resistant PCa.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Chemistry, Multidisciplinary
Xueping Hu, Jinping Pang, Jintu Zhang, Chao Shen, Xin Chai, Ercheng Wang, Haiyi Chen, Xuwen Wang, Mojie Duan, Weitao Fu, Lei Xu, Yu Kang, Dan Li, Hongguang Xia, Tingjun Hou
Summary: Different ligands binding to the glucocorticoid receptor (GR) can induce varying conformational changes and biological functions. This study explored the folding pathway of helix 12 (H12) induced by different ligands through molecular dynamics simulations and discovered a novel GR ligand, HP-19, with promising anti-inflammatory activity in the nuclear factor-kappa B signaling pathway and no adverse effects on GR transactivation functions.
Article
Biochemistry & Molecular Biology
Yoshinori Takeuchi, Yuki Murayama, Yuichi Aita, Zahra Mehrazad Saber, Samia Karkoutly, Duhan Tao, Kyoka Katabami, Chen Ye, Akito Shikama, Yukari Masuda, Yoshihiko Izumida, Takafumi Miyamoto, Takashi Matsuzaka, Yasushi Kawakami, Hitoshi Shimano, Naoya Yahagi
Summary: This study reveals the mechanism by which the glucocorticoid receptor (GR) regulates hepatic lipogenesis through the KLF15-SREBP-1 pathway during fasting. It emphasizes the importance of the hypothalamic-pituitary-adrenal (HPA) axis-regulated GR-KLF15 pathway in the regulation of lipid metabolism in the liver during fasting.
Article
Biochemistry & Molecular Biology
Lisa Zeyen, Ole Morten Seternes, Ingvild Mikkola
Summary: The p38 MAPK pathway is important for cellular stress response. It regulates downstream effectors to control inflammation and cellular processes. Dysregulation of this pathway is associated with inflammatory diseases and cancer. Glucocorticoids (GCs) secretion is a classical endocrine response to stress and is regulated by the glucocorticoid receptor (GR). The crosstalk between p38 and GR plays a role in gene expression regulation and has potential clinical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Kan Wu, Zhihong Liu, Jiayu Liang, Fuxun Zhang, Fan Zhang, Yaohui Wang, Thongher Lia, Shenzhuo Liu, Yuchun Zhu, Xiang Li
Summary: This study aims to determine the clinical and biological significance of glucocorticoid receptor (GR) expression in adrenocortical carcinoma (ACC). The research findings suggest that low GR expression is significantly correlated with excess cortisol, immune signatures, and poor survival in ACC patients.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Environmental Sciences
Xue-Ting Shi, Hua-Long Zhu, Xiao-Feng Xu, Yong-Wei Xiong, Li-Min Dai, Guo-Xiang Zhou, Wei-Bo Liu, Yu-Feng Zhang, De-Xiang Xu, Hua Wang
Summary: This study found that melatonin treatment significantly alleviated environmental cadmium-induced placental angiogenesis disorder and reduction of VEGF-A level. Mechanistically, melatonin reversed the downregulation of VEGF-A protein expression induced by environmental cadmium by inhibiting glucocorticoid receptor (GR) activation.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Biology
Shihui Guo, Zijin Chen, Yingying Dong, Yingdong Ni, Ruqian Zhao, Wenqiang Ma
Summary: Copper is essential for human health, but chronic stress can lead to disorders in copper metabolism. In this study, it was found that corticosterone impairs copper transport by down-regulating intestinal CTR1 expression via GR-mediated transcriptional inhibition. This study provides a theoretical basis for regulating copper homeostasis under chronic stress.
Article
Biochemistry & Molecular Biology
Daniela Rovito, Anna-Isavella Rerra, Vanessa Ueberschlag-Pitiot, Shilpy Joshi, Nezih Karasu, Vanessa Dacleu-Siewe, Khalil Ben Rayana, Kamar Ghaibour, Maxime Parisotto, Arnaud Ferry, Scott A. Jelinsky, Gilles Laverny, Bruno P. Klaholz, Tom Sexton, Isabelle M. L. Billas, Delphine Duteil, Daniel Metzger
Summary: Skeletal muscle size can be remodeled through various cues, with Myod1, GR, and Nrf1 identified as key players in muscle-specific enhancer-promoter communication. The study reveals that these factors control gene expression through direct contacts, transcription factor Nrf1 regulation, and Ctcf-anchored chromatin loops, orchestrating myofiber size regulation in a myofiber-specific manner. Additionally, GR negatively regulates muscle mass and strength in mice by down-regulating anabolic pathways.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Endocrinology & Metabolism
Shao-Yang Bu, Yan-Yu Zhang, Xian Zhang, Tian-Xiu Li, De-Cai Zheng, Ze-Xiang Huang, Qian Wang
Summary: The stress hormone cortisol can regulate the expression of the kiss2 gene in yellowtail clownfish by binding to the glucocorticoid receptor (GR). Kiss neurons in the yellowtail clownfish express glucocorticoid receptors in different brain regions. The promoter of the kiss2 gene in yellowtail clownfish contains binding sites for glucocorticoid receptors, estrogen receptors, androgen receptors, progesterone receptors, AP1, and C/EBP. The transcription of the kiss2 gene can be enhanced by cortisol treatment through the GRE-dependent GR pathway.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Xin Xu, Yidi Chen, Danyang Zhu, Tong Zhao, Rui Xu, Jiaying Wang, Lihong Hu, Xu Shen
Summary: This study identified a new non-steroidal GR antagonist named FX5 that effectively improved glucose homeostasis in T2DM mice by suppressing gluconeogenesis genes and antagonizing GR, highlighting its potential in T2DM treatment.
Article
Multidisciplinary Sciences
Chari M. Noddings, Ray Yu-Ruei Wang, Jill L. Johnson, David A. Agard
Summary: The study reveals the cryo-electron microscopy structure of human GR-maturation complex (GR-Hsp90-p23), showing that the GR ligand-binding domain is restored to folded, ligand-bound conformation and threaded through the Hsp90 lumen, with p23 directly stabilizing native GR through a C-terminal helix, enhancing ligand binding. This client bound to Hsp90 structure contrasts with the unfolded kinase-Hsp90 structure, indicating that Hsp90 can dictate client-specific folding outcomes through direct co-chaperone-client interactions.
Article
Biochemistry & Molecular Biology
Md. Maisum Sarwar Jyoti, Md. Rubel Rana, Md. Hasan Ali, Toshinobu Tokumoto
Summary: In this study, graphene quantum dots (GQDs) were used for the binding assay of membrane progesterone receptor alpha (mPRα). GQD-mPRα, a fluorescent GQD-conjugated mPRα, was prepared by coupling the amino groups of mPRα with GQDs. The results demonstrated the formation of a complex of GQD-mPRα and the ligand.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Paul-Emmanuel Vanderriele, Qing Wang, Anne-Marie Merillat, Frederique Ino, Gilles Aeschlimann, Xavier Ehret, David Ancin Del Olmo, Veronica Ponce de Leon, Ute I. Scholl, Denise V. Winter, Alex Odermatt, Edith Hummler, Sophia N. Verouti
Summary: Research on GR haploinsufficient Sprague Dawley rats revealed that they developed salt-sensitive hypertension on a high salt diet due to disruptions in sEH and fatty acid metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Ya-Hui Huang, Kwang-Huei Lin, Ming-Wei Lai, Chau-Ting Yeh
Summary: This study found that Mifepristone inhibits the growth of hepatocellular carcinoma (HCC) by altering the subcellular distribution of HSP60 and enhancing the formation of cytosolic GR-HSP60-survivin complexes, leading to the degradation of survivin.
Article
Cell Biology
Chandni Thakkar, Saleena Alikunju, Nandita Niranjan, Wajiha Rizvi, Ali Abbas, Maha Abdellatif, Danish Sayed
Summary: Glucocorticoids activate the Glucocorticoid receptor to regulate gene expression in cardiomyocytes, playing a crucial role in cellular homeostasis and metabolic adaptation.
CELLULAR SIGNALLING
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)