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Biomolecules
Special Issues
Inositol Phosphates in Health and Disease
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Inositol Phosphates in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (24 April 2023) | Viewed by 9911

Special Issue Editors

Dr. Ivana Vucenik

E-Mail Website
Guest Editor
School of Medicine, University of Maryland, 100 Penn Street, Baltimore, MD 21201, USA
Interests: IP6; myo-inositol; other cyclitols: methods and determination; biological role; health-promoting activities; cancer; insulin resistance; pathological calcification
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Abulkalam M. M. Shamsuddin

E-Mail Website
Guest Editor
1. Scientific Research Early Detection, Inc., San Diego, CA, USA
2. IP-6 Research, Inc., Baltimore, MD, USA
3. Department of Natural Sciences, Coppin State University, Baltimore, MD, USA
Interests: carcinogenesis; markers of precancer and cancer; cancer screening tests; cancer prevention; regulation of cell growth and differentiation; inositol phosphates
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inositol phosphates are a group of mono- to hexaphosphorylated inositols, including InsP1, InsP2, InsP3, InsP4, InsP5, InsP6, and inositol pyrophosphates. As a huge and complex family of biomolecules, Inositol phosphates are important in regulating vital cellular functions, signal transduction, energy transmission, and ion channel physiology and serving as structural components of cell membranes.

Inositol phosphates are an important group of biomolecules present in eukaryotic cells. The most abundant member of this family in nature is InsP(6), usually known as phytate. As an important component of seeds, legumes, nuts, and whole grains, it has been proven to be beneficial to human health in a variety of diseases, including cancer, PCOS, metabolic diseases, pathological calcification, and neuropsychiatric diseases. Despite all recent advances, many aspects of inositol phosphates are still not clear, so more research is needed.

This Special Issue of Biomolecules is dedicated to covering recent advances in our understanding and perspectives on inositol phosphates. Our aim is to compile a Special Issue describing recent advances in inositol phosphates in health and disease.

Dr. Ivana Vucenik
Prof. Dr. Abulkalam M. Shamsuddin
Guest Editors

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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • inositol polyphosphates (IPs)
  • IP6
  • inositol pyrophosphate (PP-Ips)
  • signal transduction
  • energy metabolism
  • anticancer activity
  • PCOS
  • metabolic diseases
  • pathological calcification
  • neuropsychiatric disease

Related Special Issue

Published Papers (4 papers)

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Research

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13 pages, 2064 KiB  
Article
Effect of Phytate (InsP6) and Other Inositol-Phosphates (InsP5, InsP4, InsP3, InsP2) on Crystallization of Calcium Oxalate, Brushite, and Hydroxyapatite
by Paula Calvó, Antònia Costa-Bauza and Felix Grases
Biomolecules 2023, 13(7), 1061; https://doi.org/10.3390/biom13071061 - 29 Jun 2023
Viewed by 806
Abstract
Pathological calcifications may consist of calcium oxalate (CaOx), hydroxyapatite (HAP), and brushite (BRU). The objective of this study was to evaluate the effect of phytate (inositol hexakisphosphate, InsP6), InsP6 hydrolysates, and individual lower InsPs (InsP5, InsP4, InsP3, and InsP2) on the crystallization of [...] Read more.
Pathological calcifications may consist of calcium oxalate (CaOx), hydroxyapatite (HAP), and brushite (BRU). The objective of this study was to evaluate the effect of phytate (inositol hexakisphosphate, InsP6), InsP6 hydrolysates, and individual lower InsPs (InsP5, InsP4, InsP3, and InsP2) on the crystallization of CaOx, HAP and BRU in artificial urine. All of the lower InsPs seem to inhibit the crystallization of calcium salts in biological fluids, although our in vitro results showed that InsP6 and InsP5 were stronger inhibitors of CaOx crystallization, and InsP5 and InsP4 were stronger inhibitors of BRU crystallization. For the specific in vitro experimental conditions we examined, the InsPs had very weak effects on HAP crystallization, although it is likely that a different mechanism is responsible for HAP crystallization in vivo. For example, calciprotein particles seem to have an important role in the formation of cardiovascular calcifications in vivo. The experimental conditions that we examined partially reproduced the in vivo conditions of CaOx and BRU crystallization, but not the in vivo conditions of HAP crystallization. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease)
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17 pages, 5746 KiB  
Article
The IP6K Inhibitor LI-2242 Ameliorates Diet-Induced Obesity, Hyperglycemia, and Hepatic Steatosis in Mice by Improving Cell Metabolism and Insulin Signaling
by Sandip Mukherjee, Molee Chakraborty, Jake Haubner, Glen Ernst, Michael DePasquale, Danielle Carpenter, James C. Barrow and Anutosh Chakraborty
Biomolecules 2023, 13(5), 868; https://doi.org/10.3390/biom13050868 - 20 May 2023
Cited by 4 | Viewed by 1834
Abstract
Obesity and nonalcoholic fatty liver disease (NAFLD) are global health concerns, and thus, drugs for the long-term treatment of these diseases are urgently needed. We previously discovered that the inositol pyrophosphate biosynthetic enzyme IP6K1 is a target in diet-induced obesity (DIO), insulin resistance, [...] Read more.
Obesity and nonalcoholic fatty liver disease (NAFLD) are global health concerns, and thus, drugs for the long-term treatment of these diseases are urgently needed. We previously discovered that the inositol pyrophosphate biosynthetic enzyme IP6K1 is a target in diet-induced obesity (DIO), insulin resistance, and NAFLD. Moreover, high-throughput screening (HTS) assays and structure−activity relationship (SAR) studies identified LI-2242 as a potent IP6K inhibitor compound. Here, we tested the efficacy of LI-2242 in DIO WT C57/BL6J mice. LI-2242 (20 mg/kg/BW daily, i.p.) reduced body weight in DIO mice by specifically reducing the accumulation of body fat. It also improved glycemic parameters and reduced hyperinsulinemia. LI-2242-treated mice displayed reduced the weight of various adipose tissue depots and an increased expression of metabolism- and mitochondrial-energy-oxidation-inducing genes in these tissues. LI-2242 also ameliorated hepatic steatosis by reducing the expression of genes that enhance lipid uptake, lipid stabilization, and lipogenesis. Furthermore, LI-2242 enhances the mitochondrial oxygen consumption rate (OCR) and insulin signaling in adipocytes and hepatocytes in vitro. In conclusion, the pharmacologic inhibition of the inositol pyrophosphate pathway by LI-2242 has therapeutic potential in obesity and NAFLD. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease)
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Review

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23 pages, 1291 KiB  
Review
Cellular and Molecular Activities of IP6 in Disease Prevention and Therapy
by Lowell Dilworth, Dewayne Stennett and Felix Omoruyi
Biomolecules 2023, 13(6), 972; https://doi.org/10.3390/biom13060972 - 10 Jun 2023
Cited by 2 | Viewed by 4295
Abstract
IP6 (phytic acid) is a naturally occurring compound in plant seeds and grains. It is a poly-phosphorylated inositol derivative that has been shown to exhibit many biological activities that accrue benefits in health and diseases (cancer, diabetes, renal lithiasis, cardiovascular diseases, etc.). IP6 [...] Read more.
IP6 (phytic acid) is a naturally occurring compound in plant seeds and grains. It is a poly-phosphorylated inositol derivative that has been shown to exhibit many biological activities that accrue benefits in health and diseases (cancer, diabetes, renal lithiasis, cardiovascular diseases, etc.). IP6 has been shown to have several cellular and molecular activities associated with its potential role in disease prevention. These activities include anti-oxidant properties, chelation of metal ions, inhibition of inflammation, modulation of cell signaling pathways, and modulation of the activities of enzymes and hormones that are involved in carbohydrate and lipid metabolism. Studies have shown that IP6 has anti-oxidant properties and can scavenge free radicals known to cause cellular damage and contribute to the development of chronic diseases such as cancers and cardiovascular diseases, as well as diabetes mellitus. It has also been shown to possess anti-inflammatory properties that may modulate immune responses geared towards the prevention of inflammatory conditions. Moreover, IP6 exhibits anti-cancer properties through the induction of cell cycle arrest, promoting apoptosis and inhibiting cancer cell growth. Additionally, it has been shown to have anti-mutagenic properties, which reduce the risk of malignancies by preventing DNA damage and mutations. IP6 has also been reported to have a potential role in bone health. It inhibits bone resorption and promotes bone formation, which may help in the prevention of bone diseases such as osteoporosis. Overall, IP6’s cellular and molecular activities make it a promising candidate for disease prevention. As reported in many studies, its anti-inflammatory, anti-oxidant, and anti-cancer properties support its inclusion as a dietary supplement that may protect against the development of chronic diseases. However, further studies are needed to understand the mechanisms of action of this dynamic molecule and its derivatives and determine the optimal doses and appropriate delivery methods for effective therapeutic use. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease)
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10 pages, 824 KiB  
Review
Application of Inositol Hexaphosphate and Inositol in Dental Medicine: An Overview
by Ana Druzijanic, Mare Kovic, Marija Roguljic, Livia Cigic, Martina Majstorovic and Ivana Vucenik
Biomolecules 2023, 13(6), 913; https://doi.org/10.3390/biom13060913 - 31 May 2023
Viewed by 1787
Abstract
Phosphorylated inositol hexaphosphate (IP6) is a naturally occurring carbohydrate, and its parent compound, myoinositol (Ins), is abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate essential cellular functions. IP6 has profound modulation effects on macrophages, [...] Read more.
Phosphorylated inositol hexaphosphate (IP6) is a naturally occurring carbohydrate, and its parent compound, myoinositol (Ins), is abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate essential cellular functions. IP6 has profound modulation effects on macrophages, which warrants further research on the therapeutic benefits of IP6 for inflammatory diseases. Here, we review IP6 as a promising compound that has the potential to be used in various areas of dentistry, including endodontics, restorative dentistry, implantology, and oral hygiene products, due to its unique structure and characteristic properties. Available as a dietary supplement, IP6 + Ins has been shown to enhance the anti-inflammatory effect associated with preventing and suppressing the progression of chronic dental inflammatory diseases. IP6 in dentistry is now substantial, and this narrative review presents and discusses the different applications proposed in the literature and gives insights into future use of IP6 in the fields of orthodontics, periodontics, implants, and pediatric dentistry. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease)
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