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Inositol in Translational Medicine
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Inositol in Translational Medicine

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

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 23246

Special Issue Editor

Prof. Dr. Vittorio Unfer

E-Mail Website
Guest Editor
AGUNCO Obstetrics & Gynecology Center, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy
Interests: biotechnology; genetics; pharmacology; pharmacokinetics; reproductive biology; reproductive endocrinology; reproductive medicine; assisted reproductive technology; pharmaceutical formulation ovary obstetrics reproduction biology cryopreservation

Special Issue Information

Dear Colleagues,

Recently, the use of inositols has received significant attention from the medical and scientific community due to their proven efficacy as preventive and adjuvant therapy for a plethora of clinical conditions.

As the research continuously provides evidence on the molecular mechanisms that underlie the observed clinical effects, it is becoming increasingly clear that Myo-inositol and D-chiro-inositol possess distinct and very peculiar physiological roles. The most recent literature demonstrates that the supplementation with either isomers or the combination of the two should be heavily tailored to a patient’s specific needs.

Combining laboratory discoveries, empirical observations, and a patient’s clinical condition is pivotal to providing the most effective inositol therapy.

This Special Issue welcomes original research articles, short communications, reviews, and commentaries related to the biomolecular properties of Myo-inositol and D-chiro-inositol or their application in all clinical fields. Pure clinical trials fall outside the scope of IJMS, but the submission of clinical reports is highly recommended if they are properly supported by molecular investigations.

Prof. Dr. Vittorio Unfer
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

  • Myo-inositol
  • D-chiro-inositol
  • inositol therapy
  • inositol metabolism
  • alpha-lactalbumin
  • polycystic ovary syndrome
  • hyperestrogenism
  • obesity
  • metabolic syndrome
  • thyroid
  • GDM
  • IVF

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Published Papers (6 papers)

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Research

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22 pages, 4670 KiB  
Article
The Potential of PIP3 in Enhancing Wound Healing
by Yossi Blitsman, Etili Hollander, Chen Benafsha, Ksenia M. Yegodayev, Uzi Hadad, Riki Goldbart, Tamar Traitel, Assaf Rudich, Moshe Elkabets and Joseph Kost
Int. J. Mol. Sci. 2024, 25(3), 1780; https://doi.org/10.3390/ijms25031780 - 1 Feb 2024
Cited by 4 | Viewed by 1632
Abstract
Given the role of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in modulating cellular processes such as proliferation, survival, and migration, we hypothesized its potential as a novel therapeutic agent for wound closure enhancement. In this study, PIP3 was examined in its free form or as a [...] Read more.
Given the role of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in modulating cellular processes such as proliferation, survival, and migration, we hypothesized its potential as a novel therapeutic agent for wound closure enhancement. In this study, PIP3 was examined in its free form or as a complex with cationic starch (Q-starch) as a carrier. The intracellular bioactivity and localization of free PIP3 and the Q-starch/PIP3 complexes were examined. Our results present the capability of Q-starch to form complexes with PIP3, facilitate its cellular membrane internalization, and activate intracellular paths leading to enhanced wound healing. Both free PIP3 and Q-starch/PIP3 complexes enhanced monolayer gap closure in scratch assays and induced amplified collagen production within HaCAT and BJ fibroblast cells. Western blot presented enhanced AKT activation by free or complexed PIP3 in BJ fibroblasts in which endogenous PIP3 production was pharmacologically inhibited. Furthermore, both free PIP3 and Q-starch/PIP3 complexes expedited wound closure in mice, after single or daily dermal injections into the wound margins. Free PIP3 and the Q-starch/PIP3 complexes inherently activated the AKT signaling pathway, which is responsible for crucial wound healing processes such as migration; this was also observed in wound assays in mice. PIP3 was identified as a promising molecule for enhancing wound healing, and its ability to circumvent PI3K inhibition suggests possible implications for chronic wound healing. Full article
(This article belongs to the Special Issue Inositol in Translational Medicine)
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17 pages, 2422 KiB  
Article
Activated Inositol Phosphate, Substrate for Synthesis of Prostaglandylinositol Cyclic Phosphate (Cyclic PIP)—The Key for the Effectiveness of Inositol-Feeding
by Antonios Gypakis, Stephan Adelt, Horst Lemoine, Günter Vogel and Heinrich K. Wasner
Int. J. Mol. Sci. 2024, 25(3), 1362; https://doi.org/10.3390/ijms25031362 - 23 Jan 2024
Cited by 1 | Viewed by 1616
Abstract
The natural cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is biosynthesized from prostaglandin E (PGE) and activated inositol phosphate (n-Ins-P), which is synthesized by a particulate rat-liver-enzyme from GTP and a precursor named inositol phosphate (pr-Ins-P), whose 5-ring phosphodiester structure is essential [...] Read more.
The natural cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is biosynthesized from prostaglandin E (PGE) and activated inositol phosphate (n-Ins-P), which is synthesized by a particulate rat-liver-enzyme from GTP and a precursor named inositol phosphate (pr-Ins-P), whose 5-ring phosphodiester structure is essential for n-Ins-P synthesis. Aortic myocytes, preincubated with [3H] myo-inositol, synthesize after angiotensin II stimulation (30 s) [3H] pr-Ins-P (65% yield), which is converted to [3H] n-Ins-P and [3H] cyclic PIP. Acid-treated (1 min) [3H] pr-Ins-P co-elutes with inositol (1,4)-bisphosphate in high performance ion chromatography, indicating that pr-Ins-P is inositol (1:2-cyclic,4)-bisphosphate. Incubation of [3H]-GTP with unlabeled pr-Ins-P gave [3H]-guanosine-labeled n-Ins-P. Cyclic PIP synthase binds the inositol (1:2-cyclic)-phosphate part of n-Ins-P to PGE and releases the [3H]-labeled guanosine as [3H]-GDP. Thus, n-Ins-P is most likely guanosine diphospho-4-inositol (1:2-cyclic)-phosphate. Inositol feeding helps patients with metabolic conditions related to insulin resistance, but explanations for this finding are missing. Cyclic PIP appears to be the key for explaining the curative effect of inositol supplementation: (1) inositol is a molecular constituent of cyclic PIP; (2) cyclic PIP triggers many of insulin’s actions intracellularly; and (3) the synthesis of cyclic PIP is decreased in diabetes as shown in rodents. Full article
(This article belongs to the Special Issue Inositol in Translational Medicine)
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10 pages, 723 KiB  
Article
D-Chiro-Inositol in Endometrial Hyperplasia: A Pilot Study
by Giuseppina Porcaro, Gabriele Bilotta, Elena Capoccia, Maria Salomé Bezerra Espinola and Cesare Aragona
Int. J. Mol. Sci. 2023, 24(12), 10080; https://doi.org/10.3390/ijms241210080 - 13 Jun 2023
Cited by 2 | Viewed by 4385
Abstract
Endometrial hyperplasia is a threatening pathology driven by unopposed estrogen stimulus. Moreover, insulin may act on the endometrium, prompting further growth. We aimed at assessing whether D-chiro-Inositol, an insulin sensitizer with estrogen-lowering properties, might improve the condition of patients with simple endometrial hyperplasia [...] Read more.
Endometrial hyperplasia is a threatening pathology driven by unopposed estrogen stimulus. Moreover, insulin may act on the endometrium, prompting further growth. We aimed at assessing whether D-chiro-Inositol, an insulin sensitizer with estrogen-lowering properties, might improve the condition of patients with simple endometrial hyperplasia without atypia. We enrolled women with simple endometrial hyperplasia without atypia and related symptoms, including abnormal uterine bleeding. We treated the patients with one tablet per day, containing 600 mg of D-chiro-inositol for six months. Patients underwent ultrasound to assess the thickness of the endometrium at baseline, after three months, and at the end of this study. Endometrial thickness went from 10.82 ± 1.15 mm to 8.00 ± 0.81 mm after three months (p < 0.001) and to 6.9 ± 1.06 mm after six months (p < 0.001 versus baseline; p < 0.001 versus three months). D-chiro-inositol treatment also improved heavy menstrual bleeding and the length of menstruation. Despite the fact that our data should be validated in larger studies with appropriate control groups, our promising results support the hypothesis that D-chiro-inositol may represent a useful treatment in the case of endometrial hyperplasia without atypia. Full article
(This article belongs to the Special Issue Inositol in Translational Medicine)
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13 pages, 1356 KiB  
Article
D-Chiro-Inositol and Myo-Inositol Induce WAT/BAT Trans-Differentiation in Two Different Human Adipocyte Models (SGBS and LiSa-2)
by Giovanni Monastra, Riccardo Gambioli, Vittorio Unfer, Gianpiero Forte, Elsa Maymo-Masip and Raffaella Comitato
Int. J. Mol. Sci. 2023, 24(8), 7421; https://doi.org/10.3390/ijms24087421 - 18 Apr 2023
Cited by 8 | Viewed by 2278
Abstract
White adipose tissue/brown adipose tissue trans-differentiation is one of the main study targets for therapies against obesity and metabolic diseases. In recent years, numerous molecules able to induce such trans-differentiation have been identified; however, their effect in obesity therapies has not been as [...] Read more.
White adipose tissue/brown adipose tissue trans-differentiation is one of the main study targets for therapies against obesity and metabolic diseases. In recent years, numerous molecules able to induce such trans-differentiation have been identified; however, their effect in obesity therapies has not been as expected. In the present study, we investigated whether myo-inositol and its stereoisomer D-chiro-inositol could be involved in the browning of white adipose tissue. Our preliminary results clearly indicate that both, at 60 μM concentration, induce the upregulation of uncoupling protein 1 mRNA expression, the main brown adipose tissue marker, and increase mitochondrial copy number as well as oxygen consumption ratio. These changes demonstrate an activation of cell metabolism. Therefore, our results show that human differentiated adipocytes (SGBS and LiSa-2), assume the features typical of brown adipose tissue after both treatments. Furthermore, in the cell lines examined, we proved that D-chiro-inositol and myo-Inositol induce an increase in the expression of estrogen receptor mRNAs, suggesting a possible modulation by these isomers. We also found an increase in the mRNA of peroxisome proliferator-activated receptor gamma, a very important target in lipid metabolism and metabolic diseases. Our results open new opportunities for the use of inositols in therapeutic strategies to counteract obesity and its metabolic complications. Full article
(This article belongs to the Special Issue Inositol in Translational Medicine)
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Review

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14 pages, 1019 KiB  
Review
The “Asthma-Polycystic Ovary Overlap Syndrome” and the Therapeutic Role of Myo-Inositol
by Gabriella Guarnieri, Matteo Iervolino, Sara Cavallone, Vittorio Unfer and Andrea Vianello
Int. J. Mol. Sci. 2023, 24(8), 6959; https://doi.org/10.3390/ijms24086959 - 9 Apr 2023
Cited by 6 | Viewed by 4224
Abstract
Asthma is a heterogeneous inflammatory disease characterized by abnormalities in immune response. Due to the inherent complexity of the disease and the presence of comorbidities, asthma control is often difficult to obtain. In asthmatic patients, an increased prevalence of irregular menstrual cycles, infertility, [...] Read more.
Asthma is a heterogeneous inflammatory disease characterized by abnormalities in immune response. Due to the inherent complexity of the disease and the presence of comorbidities, asthma control is often difficult to obtain. In asthmatic patients, an increased prevalence of irregular menstrual cycles, infertility, obesity, and insulin resistance has been reported. Given that these conditions are also common in patients with polycystic ovary syndrome (PCOS), we propose the definition of “asthma-PCOS overlap syndrome” to indicate a medical condition which shares characteristics of both diseases. The aim of this review is to analyze the links between asthma and PCOS and evaluate the therapeutic role of myo-inositol, a natural compound currently utilized in patients with PCOS, in the management of asthma patients. Full article
(This article belongs to the Special Issue Inositol in Translational Medicine)
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Other

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9 pages, 1246 KiB  
Opinion
A PCOS Paradox: Does Inositol Therapy Find a Rationale in All the Different Phenotypes?
by Vittorio Unfer, Simona Dinicola and Michele Russo
Int. J. Mol. Sci. 2023, 24(7), 6213; https://doi.org/10.3390/ijms24076213 - 25 Mar 2023
Cited by 20 | Viewed by 8028
Abstract
A recent evaluation of the published data regarding the PCOS topic has highlighted a paradox in the definition of this condition. Even though the name of the syndrome refers to ovarian dysfunction, it seems that patients diagnosed with PCOS are more likely affected [...] Read more.
A recent evaluation of the published data regarding the PCOS topic has highlighted a paradox in the definition of this condition. Even though the name of the syndrome refers to ovarian dysfunction, it seems that patients diagnosed with PCOS are more likely affected by an endocrine and metabolic issue. The term PCOS might not be appropriate to indicate the phenotypes described by the Rotterdam criteria, since the only phenotype with a gynecological issue alone is PCOS phenotype D. This novel perspective regarding how PCOS is currently defined leads the way to a reinterpretation of the entire pathological context and the treatment prescribed, such as inositols. A new point of view on the etiopathogenesis of the disease completely changes the current meaning of PCOS and consequently the therapeutic rationale evaluated to date. Full article
(This article belongs to the Special Issue Inositol in Translational Medicine)
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