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Nuclear Receptors in Diseases
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Nuclear Receptors in Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 December 2024 | Viewed by 2269

Special Issue Editor

Dr. Roberto Palacios-Ramirez

E-Mail Website
Guest Editor
Facultad de Medicina, Universidad de Valladolid, 45003 Valladolid, Spain
Interests: mineralocorticoid receptors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The nuclear receptor superfamily comprises 48 members in humans. Nuclear receptors are ligand-inducible transcription factors, responsible for the action of hydrophobic signaling molecules, such as steroid hormones, thyroid hormones, vitamin A (retinolids), vitamin D, and some metabolic signals. These hydrophobic signaling molecules have significant physiological roles in growth, development, metabolism, immunity, and homeostasis, and dysregulation of nuclear receptors and their ligand functions closely involved in the pathogenesis of various diseases, such as cancer, cardiovascular diseases, autoimmune diseases, metabolic syndrome, and so on.

In this Special Issue, we are pleased to invite original articles and reviews that cover the participation of nuclear receptor in homeostasis and pathology, and some potential therapeutic interventions.

Dr. Roberto Palacios-Ramirez
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nuclear receptors
  • hormone receptors
  • orphan receptors
  • retinoid receptors
  • metabolic diseases
  • cancers
  • drug metabolism

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Published Papers (2 papers)

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Research

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15 pages, 7211 KiB  
Article
Glucocorticoid Receptor Isoforms in Breast Cancer Raise Implications for Personalised Supportive Therapies
by Henriett Butz, Viktória Vereczki, Barna Budai, Gábor Rubovszky, Rebeka Gyebrovszki, Ramóna Vida, Erika Szőcs, Bence Gerecs, Andrea Kohánka, Erika Tóth, István Likó, Imre Kacskovics and Attila Patócs
Int. J. Mol. Sci. 2024, 25(21), 11813; https://doi.org/10.3390/ijms252111813 - 3 Nov 2024
Viewed by 1032
Abstract
Glucocorticoid receptor (GR) activation may promote metastasis in oestrogen receptor-negative and triple-negative breast cancer (TNBC). However, the role of the GRβ isoform, which has opposing effects to the main isoform, has not been studied in clinical samples. We aimed to analyse the intracellular [...] Read more.
Glucocorticoid receptor (GR) activation may promote metastasis in oestrogen receptor-negative and triple-negative breast cancer (TNBC). However, the role of the GRβ isoform, which has opposing effects to the main isoform, has not been studied in clinical samples. We aimed to analyse the intracellular localisation of total GR and GRβ in vitro using plasmid constructs and fluorescent immunocytochemistry. Additionally, our goal was to perform immunostaining for total GR and GRβ on two cohorts: (i) on 194 clinical breast cancer samples to compare the expression in different molecular subtypes, and (ii) on 161 TNBC samples to analyse the association of GR with survival. We supplemented our analysis with RNA data from 1097 TNBC cases. We found that in the absence of the ligand, GR resided in the cytoplasm of breast cancer cells, while upon ligand activation, it translocated to the nucleus. A negative correlation was found between cytoplasmic GRtotal and Ki67 in luminal A tumours, while the opposite trend was observed in TNBC samples. Tumours with strong lymphoid infiltration showed higher cytoplasmic GRtotal staining compared to those with weaker infiltration. Patients with high nuclear GRtotal staining had shorter progression-free survival in univariate analysis. High cytoplasmic GRβ was a marker for better overall survival in multivariate analysis (10-year overall survival HR [95% CI]: 0.46 [0.22–0.95], p = 0.036). As a conclusions, this study is the first to investigate GRβ expression in breast tumours. Different expression and cellular localisation of GRtotal and GRβ were observed in the context of molecular subtypes, underscoring the complex role of GR in breast cancer. An inverse association between cytoplasmic GRtotal and the Ki67 proliferation index was observed in luminal A and TNBC. Regarding the impact of GR on outcomes in TNBC patients, while cytoplasmic GRβ was associated with a better prognosis, patients with nuclear GRtotal staining may be at a higher risk of disease progression, as it negatively affects survival. Caution should be exercised when using glucocorticoids in patients with nuclear GR staining, as it may negatively impact survival. Full article
(This article belongs to the Special Issue Nuclear Receptors in Diseases)
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Review

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24 pages, 1826 KiB  
Review
Mineralocorticoid Receptor and Sleep Quality in Chronic Kidney Disease
by Juan de la Puente-Aldea, Oscar Lopez-Llanos, Daniel Horrillo, Hortensia Marcos-Sanchez, Sandra Sanz-Ballesteros, Raquel Franco, Frederic Jaisser, Laura Senovilla and Roberto Palacios-Ramirez
Int. J. Mol. Sci. 2024, 25(22), 12320; https://doi.org/10.3390/ijms252212320 - 16 Nov 2024
Viewed by 965
Abstract
The classical function of the mineralocorticoid receptor (MR) is to maintain electrolytic homeostasis and control extracellular volume and blood pressure. The MR is expressed in the central nervous system (CNS) and is involved in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis as well [...] Read more.
The classical function of the mineralocorticoid receptor (MR) is to maintain electrolytic homeostasis and control extracellular volume and blood pressure. The MR is expressed in the central nervous system (CNS) and is involved in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis as well as sleep physiology, playing a role in the non-rapid eye movement (NREM) phase of sleep. Some patients with psychiatric disorders have very poor sleep quality, and a relationship between MR dysregulation and this disorder has been found in them. In addition, the MR is involved in the regulation of the renal peripheral clock. One of the most common comorbidities observed in patients with chronic kidney disease (CKD) is poor sleep quality. Patients with CKD experience sleep disturbances, including reduced sleep duration, sleep fragmentation, and insomnia. To date, no studies have specifically investigated the relationship between MR activation and CKD-associated sleep disturbances. However, in this review, we analyzed the environment that occurs in CKD and proposed two MR-related mechanisms that may be responsible for these sleep disturbances: the circadian clock disruption and the high levels of MR agonist observed in CKD. Full article
(This article belongs to the Special Issue Nuclear Receptors in Diseases)
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