International Journal of Molecular Sciences

Journal Browser

► Journal Browser

Special Issue Information

Dear Colleagues,

Systemic homeostasis is maintained by synchronous and regulated messaging within our body. Hormones, endogenous peptides and growth factors play significant roles as agents for conveying this message between different cell types and organ systems. Following disease pathologies and during aging, these agents of communication start behaving in a random manner, providing false signals to target cells and tissues. An altered or improperly regulated secretion could initiate a disease condition, or aggravate an existing one, or accelerate the process of aging. We welcome any original submissions which are focused on studying the role of these agents that participate in this interorgan or intercellular cross-talk following normal states and disease conditions, and also during aging.

The scope of this Special Issue is to shed light on the pharmacological effects of endogenous hormones, peptides and growth factors as crucial communicators during normal physiology, disease states and aging. We will be accepting submissions in the form of original articles and review articles that are focused on studying the molecular mechanisms and influences of hormones, endogenous peptides and growth factors in regulating disease states and aging. We look forward to receiving your original and outstanding contributions for this Special Issue.

Dr. Prasanth Puthanveetil
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

hormones
peptides
growth factors
pharmacological signaling
aging and endogenous secretions
systems cross-talk

Published Papers (2 papers)

Download All Papers

Research

Jump to: Review

17 pages, 2264 KiB

Open AccessArticle

High-Throughput In Vitro Screening Identified Nemadipine as a Novel Suppressor of Embryo Implantation

by Xian Chen, Sudini Ranshaya Fernando, Yin-Lau Lee, William Shu-Biu Yeung, Ernest Hung-Yu Ng, Raymond Hang-Wun Li and Kai-Fai Lee

Int. J. Mol. Sci. 2022, 23(9), 5073; https://doi.org/10.3390/ijms23095073 - 3 May 2022

Cited by 1 | Viewed by 1926

Abstract

Current contraceptive methods interfere with folliculogenesis, fertilization, and embryo implantation by physical or hormonal approaches. Although hormonal contraceptive pills are effective in regulating egg formation, they are less effective in preventing embryo implantation. To explore the use of non-hormonal compounds that suppress embryo implantation, we established a high-throughput spheroid-endometrial epithelial cell co-culture assay to screen the Library of Pharmacologically Active Compounds (LOPAC) for compounds that affect trophoblastic spheroid (blastocyst surrogate) attachment onto endometrial epithelial Ishikawa cells. We identified 174 out of 1280 LOPAC that significantly suppressed BeWo spheroid attachment onto endometrial Ishikawa cells. Among the top 20 compounds, we found the one with the lowest cytotoxicity in Ishikawa cells, P11B5, which was later identified as Nemadipine-A. Nemadipine-A at 10 µM also suppressed BeWo spheroid attachment onto endometrial epithelial RL95-2 cells and primary human endometrial epithelial cells (hEECs) isolated from LH +7/8-day endometrial biopsies. Mice at 1.5 days post coitum (dpc) treated with a transcervical injection of 100 µg/kg Nemadipine-A or 500 µg/kg PRI-724 (control, Wnt-inhibitor), but not 10 µg/kg Nemadipine-A, suppressed embryo implantation compared with controls. The transcript expressions of endometrial receptivity markers, integrin αV (ITGAV) and mucin 1 (MUC1), but not β-catenin (CTNNB1), were significantly decreased at 2.5 dpc in the uterus of treated mice compared with controls. The reduction of embryo implantation by Nemadipine-A was likely mediated through suppressing endometrial receptivity molecules ITGAV and MUC1. Nemadipine-A is a potential novel non-hormonal compound for contraception. Full article

(This article belongs to the Special Issue Pharmacology of Hormones, Peptides and Growth Factors in Systemic Cross-Talk)

► Show Figures

Figure 1

Review

Jump to: Research

13 pages, 703 KiB

Open AccessReview

The Divergent Effects of Ovarian Steroid Hormones in the MCF-7 Model for Luminal A Breast Cancer: Mechanistic Leads for Therapy

by Nitin T. Telang

Int. J. Mol. Sci. 2022, 23(9), 4800; https://doi.org/10.3390/ijms23094800 - 27 Apr 2022

Cited by 8 | Viewed by 2167

Abstract

The growth modulating effects of the ovarian steroid hormones 17β-estradiol (E₂) and progesterone (PRG) on endocrine-responsive target tissues are well established. In hormone-receptor-positive breast cancer, E₂ functions as a potent growth promoter, while the function of PRG is less defined. In the hormone-receptor-positive Luminal A and Luminal B molecular subtypes of clinical breast cancer, conventional endocrine therapy predominantly targets estrogen receptor function and estrogen biosynthesis and/or growth factor receptors. These therapeutic options are associated with systemic toxicity, acquired tumor resistance, and the emergence of drug-resistant cancer stem cells, facilitating the progression of therapy-resistant disease. The limitations of targeted endocrine therapy emphasize the identification of nontoxic testable alternatives. In the human breast, carcinoma-derived hormone-receptor-positive MCF-7 model treatment with E₂ within the physiological concentration range of 1 nM to 20 nM induces progressive growth, upregulated cell cycle progression, and downregulated cellular apoptosis. In contrast, treatment with PRG at the equimolar concentration range exhibits dose-dependent growth inhibition, downregulated cell-cycle progression, and upregulated cellular apoptosis. Nontoxic nutritional herbs at their respective maximum cytostatic concentrations (IC₉₀) effectively increase the E₂ metabolite ratio in favor of the anti-proliferative metabolite. The long-term exposure to the selective estrogen-receptor modulator tamoxifen selects a drug-resistant phenotype, exhibiting increased expressions of stem cell markers. The present review discusses the published evidence relevant to hormone metabolism, growth modulation by hormone metabolites, drug-resistant stem cells, and growth-inhibitory efficacy of nutritional herbs. Collectively, this evidence provides proof of the concept for future research directions that are focused on novel therapeutic options for endocrine therapy-resistant breast cancer that may operate via E₂- and/or PRG-mediated growth regulation. Full article

(This article belongs to the Special Issue Pharmacology of Hormones, Peptides and Growth Factors in Systemic Cross-Talk)

► Show Figures