Article
Cell Biology
Xiangyu Zhao, Ting Peng, Xunhong Cao, Yingping Hou, Ruifeng Li, Tingting Han, Zeying Fan, Ming Zhao, Yingjun Chang, Hebin Chen, Cheng Li, Xiaojun Huang
Summary: A study found that G-CSF treatment suppresses IFN-y secretion in NK cells. The mechanism involves the activation of GRs, which promote interactions between SOCS1 promoters and enhancers, as well as increasing the expression of SOCS1.
Review
Medicine, Research & Experimental
Lijuan Mao, Wei Wei, Jingyu Chen
Summary: Glucocorticoids (GCs) are steroid hormones that regulate various homeostatic functions in the body through the binding of glucocorticoid receptor (GR). GR signals are biased, with variations in different tissue cells, disease states, and ligands. This bias regulation of GR signaling depends on ligand-induced metameric regulation, protein post-translational modifications, assembly at response elements, context-specific assembly, and intercellular differences. Selective GR agonists and modulators (SEGRAMs) have been developed to bias therapeutic outcomes towards expected effects by influencing GR-mediated gene expression. This paper reviews the bias regulation and mechanism of GR, as well as the progress in drug research.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Wesuk Kang, Dabin Choi, Jiyun Roh, Yearim Jung, Yoojeong Ha, Suhjin Yang, Taesun Park
Summary: This study examined the role of cyclic adenosine monophosphate (cAMP) in the activation of glucocorticoid receptors (GRs) and its associated mechanisms. The results showed that cAMP enhancement did not affect glucocorticoid signaling under normal conditions, but could modulate it in response to stress. The study also revealed that cAMP upregulation triggers the activation of the extracellular signal-regulated kinase (ERK) pathway, which influences GR translocation and activity. These findings highlight the context-dependent role of cAMP signaling in managing glucocorticoid signaling and its potential therapeutic application in stress-related conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ioanna Kokkinopoulou, Paraskevi Moutsatsou
Summary: Mitochondria play a crucial role in cellular processes beyond energy production, being involved in calcium homeostasis, ROS generation, cell death, thermogenesis, and biosynthesis. Glucocorticoids regulate mitochondrial gene expression and metabolism, with GR directly influencing mitochondrial functions including apoptosis and inflammation. Further studies are needed to fully understand the mechanisms of GR translocation and its impact on mitochondrial processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Clarissa Silva Martins, Margaret de Castro
Summary: This review summarizes the major factors that influence individual glucocorticoid sensitivity/resistance, highlighting the tissue-specific fine-tuning of GC action.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dabin Choi, Wesuk Kang, Soyoon Park, Bomin Son, Taesun Park
Summary: For several decades, excessive glucocorticoids (GCs) have been known to inhibit collagen synthesis and accelerate skin aging, but the molecular mechanisms involved are not well understood. In this study, the researchers identified potential glucocorticoid receptor (GR) target genes that may contribute to the inhibition of collagen synthesis. They confirmed that dexamethasone, a synthetic GC, activates canonical GR signaling in dermal fibroblasts and identified six candidate genes involved in the GC-mediated inhibition of collagen synthesis. This study provides insights into the molecular mechanisms of GC-mediated skin aging and lays the foundation for further research on the biological characteristics of individual GR target genes.
Article
Immunology
Richa Mishra, Pandikannan Krishnamoorthy, Himanshu Kumar
Summary: Host innate immunity plays a crucial role in combating microbial infections, but some pathogenic bacteria have strategies to evade the immune system. MicroRNAs are believed to modulate host immune responses during bacterial infections, with miR-30e-5p identified as a potential candidate for HDT.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Sara La Manna, Sara Fortuna, Marilisa Leone, Flavia A. Mercurio, Ilaria Di Donato, Rosa Bellavita, Paolo Grieco, Francesco Merlino, Daniela Marasco
Summary: This study aimed to optimize the peptide structure and improve the biological activity of KIR-SOCS1. By utilizing different techniques, the researchers found that the size of the cyclic structure was crucial for its interaction with JAK2, and substituting native residues with un-natural building blocks enhanced the stability and affinity. These findings contribute to increasing the structural knowledge required for the recognition of SOCS1/JAK2 and advancing towards the development of more drug-like compounds.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Sirvan Khalighi, Peronne Joseph, Deepak Babu, Salendra Singh, Thomas LaFramboise, Kishore Guda, Vinay Varadan
Summary: SYSMut is an extendable systems biology platform that can infer the biological consequences of gene mutations by integrating multiomics profiles. It has been used to identify driver genes across 29 cancers and discover new therapeutic targets in head and neck squamous cell cancer.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Endocrinology & Metabolism
Rachel M. B. Bell, Elisa Villalobos, Mark Nixon, Allende Miguelez-Crespo, Lee Murphy, Angie Fawkes, Audrey Coutts, Matthew G. F. Sharp, Martha Koerner, Emma Allan, Onno C. Meijer, Rene Houtman, Alex Odermatt, Katharina R. Beck, Scott G. Denham, Patricia Lee, Natalie Z. M. Homer, Brian R. Walker, Ruth A. Morgan
Summary: Carbonyl reductase 1 regulates glucocorticoid and mineralocorticoid receptor activation in adipose tissue, influencing glucose homeostasis in lean mice.
MOLECULAR METABOLISM
(2021)
Article
Cell Biology
Henriett Butz, Eva Saskoi, Lilla Krokker, Viktoria Vereczki, Alan Alpar, Istvan Liko, Erika Toth, Erika Szocs, Mihaly Cserepes, Katalin Nagy, Imre Kacskovics, Attila Patocs
Summary: This study aimed to uncover the context-dependent action of glucocorticoid receptors (GR) in breast cancer. Through multiple cohorts, it was found that GR expression is higher in ER- breast cancer cells and GR-regulated genes are mainly involved in cell migration. The study also revealed that GR action is independent of ligand availability, highlighting its ligand-independent role in breast cancer. Therefore, caution should be applied in the interpretation of immunohistochemistry results, and the importance of GR in disease progression, particularly in cell migration, is emphasized.
Article
Medicine, General & Internal
Arno Teblick, Lisa Van Dyck, Nathalie Van Aerde, Sarah Van der Perre, Lies Pauwels, Inge Derese, Yves Debaveye, Pieter J. Wouters, Ilse Vanhorebeek, Lies Langouche, Greet Van den Berghe
Summary: This study found tissue-specific expression changes of receptor-regulatory factors in critically ill patients, which adaptively guide the action of glucocorticoids in different tissues. These findings are important for understanding the importance of glucocorticoid resistance and glucocorticoid treatment.
Review
Biochemistry & Molecular Biology
Nicolas C. Nicolaides, Evangelia Charmandari
Summary: Glucocorticoids play a crucial role in restoring homeostasis in response to stress. Inappropriate glucocorticoid signaling can lead to pathological conditions, emphasizing the importance of understanding these rare endocrinologic diseases and improving therapeutic management through advancements in structural, molecular, and cellular biology, as well as biotechnology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Endocrinology & Metabolism
Nicolas C. Nicolaides
Summary: Glucocorticoid receptors play a crucial role in various cellular processes and physiological functions. Recent studies have shown that the beta isoform of the receptor, GR beta, has important functions in cellular homeostasis and is involved in endocrine physiology and pathophysiology.
Article
Cardiac & Cardiovascular Systems
Hannah M. Costello, Georgios Krilis, Celine Grenier, David Severs, Alicja Czopek, Jessica R. Ivy, Mark Nixon, Megan C. Holmes, Dawn E. W. Livingstone, Ewout J. Hoorn, Neeraj Dhaun, Matthew A. Bailey
Summary: High salt intake activates the hypothalamic-pituitary-adrenal axis, leading to excess glucocorticoid levels and impacting glucocorticoid biology.
CARDIOVASCULAR RESEARCH
(2023)
Article
Multidisciplinary Sciences
Nirmala Parajuli, Stephen Shrum, Julia Tobacyk, Alex Herb, John M. Arthur, Lee Ann MacMillan-Crow
Review
Biochemistry & Molecular Biology
John C. Marecki, Nirmala Parajuli, John P. Crow, Lee Ann MacMillan-Crow
ANTIOXIDANTS & REDOX SIGNALING
(2014)
Article
Immunology
Lara Hannesdottir, Piotr Tymoszuk, Nirmala Parajuli, Marie-Helene Wasmer, Sonja Philipp, Nina Daschil, Sebak Datta, Johann-Benedikt Koller, Christoph H. Tripp, Patrizia Stoitzner, Elisabeth Mueller-Holzner, Gerrit Jan Wiegers, Veronika Sexl, Andreas Villunger, Wolfgang Doppler
EUROPEAN JOURNAL OF IMMUNOLOGY
(2013)
Article
Biochemistry & Molecular Biology
Nirmala Parajuli, Akira Marine, Sloane Simmons, Hamida Saba, Tanecia Mitchell, Takahiko Shimizu, Takuji Shirasawa, Lee Ann MacMillan-Crow
FREE RADICAL BIOLOGY AND MEDICINE
(2011)
Article
Cell Biology
Sebak Datta, Nirmala Parajuli, Piotr Tymoszuk, Eleonora Ottina, Walther Parson, Roswitha Sgonc, Andreas Villunger, Wolfgang Doppler
JOURNAL OF LEUKOCYTE BIOLOGY
(2014)
Article
Multidisciplinary Sciences
Nirmala Parajuli, Lia H. Campbell, Akira Marine, Kelvin G. M. Brockbank, Lee Ann MacMillan-Crow
Article
Cell Biology
Julia Tobacyk, Nirmala Parajuli, Stephen Shrum, John P. Crow, Lee Ann MacMillan-Crow
Article
Biochemistry & Molecular Biology
Stephen Shrum, Julia Tobacyk, Sorena Lo, Nirmala Parajuli, Lee Ann MacMillan-Crow
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2020)
Review
Biochemistry & Molecular Biology
Sorena B. Lo, Richard T. Blaszak, Nirmala Parajuli
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Madison McGraw, David Miller, Sorena Lo, Nirmala Parajuli
Summary: Cold storage-mediated inflammation is a significant concern in kidney transplantation, but the mechanisms involved are not well understood. This study investigated the role of STAT proteins, particularly STAT1 and STAT3, using in vivo and in vitro models. The results showed increased expression of IFN-gamma and STAT1 after cold storage and transplantation. Additionally, dephosphorylation of STAT3 was observed after cold storage, indicating dysregulation of anti-inflammatory signaling. In vitro experiments further demonstrated increased IFN-gamma expression and downstream activation of STAT1 and iNOS after cold storage and rewarming. These findings suggest that targeting Jak/STAT signaling during cold storage could potentially improve transplant outcomes for kidneys from deceased donors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physiology
Sorena Lo, Li Jiang, Savannah Stacks, Haixia Lin, Nirmala Parajuli
Summary: This study revealed that cold storage leads to aberrant activation of complement components in renal grafts following transplantation, with increased levels of C3 and C5b-9. Additionally, cold storage induced local C3 biogenesis in renal proximal cells/tubules, and TNF-alpha was found to promote C3 biogenesis and activation in renal proximal tubular cells.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Physiology
Sorena Lo, Lee Ann MacMillan-Crow, Nirmala Parajuli
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2019)
Article
Physiology
Naeem K. Patil, Nirmala Parajuli, Lee Ann MacMillan-Crow, Philip R. Mayeux
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2014)
Article
Physiology
Nirmala Parajuli, Lee Ann MacMillan-Crow
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2013)
Article
Transplantation
Sorena Lo, Stephanie D. Byrum, Alan J. Tackett, Nirmala Parajuli
TRANSPLANTATION DIRECT
(2019)