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1.
Impact of myo-inositol treatment in women with polycystic ovary syndrome in assisted reproductive technologies.
Merviel, P, James, P, Bouée, S, Le Guillou, M, Rince, C, Nachtergaele, C, Kerlan, V
Reproductive health. 2021;(1):13
Abstract
Polycystic ovary syndrome (PCOS) is marked in 30 to 40% by insulin resistance and hyperandrogenism. Myo-inositol (MI) increases insulin sensitivity, decreases hyperandrogenism and improves the menstrual cycle. Its effect during assisted reproductive technologies (ART) has been studied by many authors. We conducted a review of the literature on the impact of MI administration in PCOS women in assisted reproductive technologies. Myo-inositol is effective in normalizing ovarian function, improving oocyte and embryo quality in PCOS, however further evaluations by large multicentre randomized controlled trials are needed to assess the clinical pregnancy and live birth rates in ART.
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2.
Inositol and vitamin D may naturally protect human reproduction and women undergoing assisted reproduction from Covid-19 risk.
Bezerra Espinola, MS, Bertelli, M, Bizzarri, M, Unfer, V, Laganà, AS, Visconti, B, Aragona, C
Journal of reproductive immunology. 2021;:103271
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Abstract
In late 2019, the new Coronavirus has been identified in the city of Wuhan then COVID-19 spreads like wildfire in the rest of the world. Pregnant women represent a risk category for increased abortion rates and vertical transmission with adverse events on the newborns has been recently confirmed. The scientific world is struggling for finding an effective cure for counteracting symptomatology. Today, there are many therapeutic proposes but none of them can effectively counteract the infection. Moreover, many of these compounds show important side effects not justifying their use. Scientific literature reports an immune system over-reaction through interleukins-6 activation. In this regard, the possibility to control the immune system represents a possible strategy for counteracting the onset of COVID-19 symptomatology. Vitamin D deficiency shows increased susceptibility to acute viral respiratory infections. Moreover, Vitamin D seems involved in host protection from different virus species by modulating activation and release of cytokines. Myo-inositol down-regulates the expression of IL-6 by phosphatidyl-inositol-3-kinase (PI3K) pathway. Furthermore, myo-inositol is the precursor of phospholipids in the surfactant and it is applied for inducing surfactant synthesis in infants for treating respiratory distress syndrome (RDS). This review aims to summarize the evidence about COVID-19 infection in pregnant women and to encourage the scientific community to investigate the use of Vitamin D and Myo-inositol which could represent a possible preventive treatment for pregnant women or women undergoing assisted reproductive technologies (ART).
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Inositol polyphosphate-protein interactions: Implications for microbial pathogenicity.
Lev, S, Bowring, B, Desmarini, D, Djordjevic, JT
Cellular microbiology. 2021;(6):e13325
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Abstract
Inositol polyphosphates (IPs) and inositol pyrophosphates (PP-IPs) regulate diverse cellular processes in eukaryotic cells. IPs and PP-IPs are highly negatively charged and exert their biological effects by interacting with specific protein targets. Studies performed predominantly in mammalian cells and model yeasts have shown that IPs and PP-IPs modulate target function through allosteric regulation, by promoting intra- and intermolecular stabilization and, in the case of PP-IPs, by donating a phosphate from their pyrophosphate (PP) group to the target protein. Technological advances in genetics have extended studies of IP function to microbial pathogens and demonstrated that disrupting PP-IP biosynthesis and PP-IP-protein interaction has a profound impact on pathogenicity. This review summarises the complexity of IP-mediated regulation in eukaryotes, including microbial pathogens. It also highlights examples of poor conservation of IP-protein interaction outcome despite the presence of conserved IP-binding domains in eukaryotic proteomes.
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The Role of Inositol in Thyroid Physiology and in Subclinical Hypothyroidism Management.
Benvenga, S, Nordio, M, Laganà, AS, Unfer, V
Frontiers in endocrinology. 2021;:662582
Abstract
Myo-Inositol (MYO) is the most abundant stereoisomer of inositols' family, cyclic polyols with 6 hydroxyl groups. Myo-Inositol has a relevant role in thyroid function and autoimmune diseases, as a precursor of phosphoinositides that takes part in the phosphatidylinositol (PI) signal transduction pathway. Among phosphoinositides, phosphatidylinositol 4,5- bisphosphate (PIP2) is the precursor of inositol triphosphates (IP3), second messenger of several hormones including thyroid-stimulating hormone (TSH). As a second messenger in the phospholipase C (PLC)-dependent inositol phosphate Ca2+/DAG pathway, Myo-Inositol is essential to produce H2O2 required for the synthesis of thyroid hormones. Consequently, depletion of Myo-Inositol or impaired inositol dependent TSH signaling pathway may predispose to the development of some thyroid diseases, such as hypothyroidism. Many clinical studies have shown that after treatment with Myo-Inositol plus Selenium (MYO+Se), TSH levels significantly decreased in patients with subclinical hypothyroidism with or without autoimmune thyroiditis. The TSH reduction was accompanied by a decline of antithyroid autoantibodies. Moreover, Myo-Inositol supplementation seemed to be involved also in the management of thyroidal benign nodules, with a possible effect in the size reduction. This review proposes a summary of the role of inositol, especially of Myo-Inositol, in the thyroidal physiology and its contribution on the management of some thyroid diseases.
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Breakthroughs in the Use of Inositols for Assisted Reproductive Treatment (ART).
Facchinetti, F, Espinola, MSB, Dewailly, D, Ozay, AC, Prapas, N, Vazquez-Levin, M, Wdowiak, A, Unfer, V, ,
Trends in endocrinology and metabolism: TEM. 2020;(8):570-579
Abstract
It is well known that myo-inositol (MI) and D-chiro-inositol (DCI) are insulin-sensitizing agents, and MI is of proven utility in polycystic ovary syndrome (PCOS). In addition, MI plays a pivotal role in the physiology of reproduction, and has beneficial effects on the development of oocytes, spermatozoa, and embryos. By contrast, DCI has little effect on spermatozoa, but high concentrations in the ovary can negatively affect the quality of oocytes and the blastocyst. Overall, the evidence in the literature supports the beneficial effects of MI in both female and male reproduction, warranting clinical use of MI in assisted reproductive treatment (ART).
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Are Inositol Polyphosphates the Missing Link in Dynamic Cullin RING Ligase Regulation by the COP9 Signalosome?
Zhang, X, Rao, F
Biomolecules. 2019;(8)
Abstract
The E3 ligase activity of Cullin RING Ligases (CRLs) is controlled by cycles of neddylation/deneddylation and intimately regulated by the deneddylase COP9 Signalosome (CSN), one of the proteasome lid-CSN-initiation factor 3 (PCI) domain-containing "Zomes" complex. Besides catalyzing the removal of stimulatory Cullin neddylation, CSN also provides a docking platform for other proteins that might play a role in regulating CRLs, notably protein kinases and deubiquitinases. During the CRL activity cycle, CRL-CSN complexes are dynamically assembled and disassembled. Mechanisms underlying complex dynamics remain incompletely understood. Recently, the inositol polyphosphate metabolites (IP6, IP7) and their metabolic enzymes (IP5K, IP6K) have been discovered to participate in CRL-CSN complex formation as well as stimulus-dependent dissociation. Here we discuss these mechanistic insights in light of recent advances in elucidating structural basis of CRL-CSN complexes.
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Non-pharmacological management of gestational diabetes: The role of myo-inositol.
Guardo, FD, Currò, JM, Valenti, G, Rossetti, P, Di Gregorio, LM, Conway, F, Chiofalo, B, Garzon, S, Bruni, S, Rizzo, G
Journal of complementary & integrative medicine. 2019;(2)
Abstract
Gestational diabetes mellitus (GDM) is the most common metabolic disorder occurring in pregnancy. GDM plays an important role in the current diabetes epidemic: exposure to a high glycemic environment during the early stages of development increases the risk of the fetus to develop type two diabetes mellitus (T2DM) in adult life. Various cardiometabolic risk factors are linked to GDM. A thorough knowledge of the risk factors and genes involved in the development of GDM, along with an understanding of the underlying pathophysiological mechanisms are crucial to properly identify patients at risk of developing this condition. There is growing evidence showing that myo-inositol, combined with an appropriate therapeutic regimen for GDM, can provide additional benefits to the patient. The aim of this review is to analyze the role of inositol isomers - especially myo-inositol (MYO-INS) - in the treatment of patients with GDM.
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Diet and Nutritional Interventions with the Special Role of Myo-Inositol in Gestational Diabetes Mellitus Management. An Evidence-Based Critical Appraisal.
Reyes-Muñoz, E, Guardo, FD, Ciebiera, M, Kahramanoglu, I, Sathyapalan, T, Lin, LT, Shah, M, Karaman, E, Fan, S, Zito, G, et al
Current pharmaceutical design. 2019;(22):2467-2473
Abstract
BACKGROUND Gestational Diabetes Mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, represents one of the most common maternal-fetal complications during pregnancy and it is associated with poor perinatal outcomes. To date, GDM is a rising condition over the last decades coinciding with the ongoing epidemic of obesity and Type 2 Diabetes Mellitus (T2DM). OBJECTIVE The aim of this review is to discuss the role of diet and nutritional interventions in preventing GDM with the explanation of the special role of myo-inositol (MI) in this matter. METHODS We performed an overview of the most recent literature data on the subject with particular attention to the effectiveness of diet and nutritional interventions in the prevention of GDM with the special role of MI. RESULTS Nutritional intervention and physical activity before and during pregnancy are mandatory in women affected by GDM. Moreover, the availability of insulin-sensitizers such as different forms of inositol has dramatically changed the scenario, allowing the treatment of several metabolic diseases, such as those related to glucose dysbalance. Although the optimal dose, frequency, and form of MI administration need to be further investigated, diet supplementation with MI appears to be an attractive alternative for the GDM prevention as well as for the reduction of GDM-related complications. CONCLUSIONS More studies should be conducted to prove the most effective nutritional intervention in GDM. Regarding the potential effectiveness of MI, further evidence in multicenter, randomized controlled trials is needed to draw firm conclusions.
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Myo-Inositol for the Prevention of Gestational Diabetes Mellitus. A Brief Review.
D'Anna, R, Santamaria, A, Alibrandi, A, Corrado, F, DI Benedetto, A, Facchinetti, F
Journal of nutritional science and vitaminology. 2019;(Supplement):S59-S61
Abstract
Gestational Diabetes Mellitus (GDM) is one of the most frequent complications of pregnancy and is characterized by a carbohydrate intolerance which is diagnosed with the oral glucose tolerance test. The prevalence of GDM in our population is about 12%, but risk factors like a previous GDM, ethnicity, a parent with diabetes mellitus type 2 and maternal overweight may increase its occurrence. Complications of GDM are a pre-term birth (before 37 wk gestation), macrosomia (birth weight ≥4 kg) and gestational hypertension. Actually, GDM is principally treated with diet and, if it is necessary, with insulin; but the challenge is the prevention of GDM. Among the measures used, changes in life-style (diet+exercise) failed to prevent GDM whereas metformin showed conflicting results. A promising supplement is myo-inositol (MI) which was given from first trimester until delivery to women at risk for GDM reporting a significant decrease in GDM occurrence by more than 60% comparing to the placebo group. Recently, a secondary analysis from 3 randomized controlled trials demonstrated that MI may also significantly reduce some of GDM complications such as pre-term birth and macrosomia with a favorable impact on mother and fetus well being.
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The Function of Inositol Phosphatases in Plant Tolerance to Abiotic Stress.
Jia, Q, Kong, D, Li, Q, Sun, S, Song, J, Zhu, Y, Liang, K, Ke, Q, Lin, W, Huang, J
International journal of molecular sciences. 2019;(16)
Abstract
Inositol signaling is believed to play a crucial role in various aspects of plant growth and adaptation. As an important component in biosynthesis and degradation of myo-inositol and its derivatives, inositol phosphatases could hydrolyze the phosphate of the inositol ring, thus affecting inositol signaling. Until now, more than 30 members of inositol phosphatases have been identified in plants, which are classified intofive families, including inositol polyphosphate 5-phosphatases (5PTases), suppressor of actin (SAC) phosphatases, SAL1 phosphatases, inositol monophosphatase (IMP), and phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-related phosphatases. The current knowledge was revised here in relation to their substrates and function in response to abiotic stress. The potential mechanisms were also concluded with the focus on their activities of inositol phosphatases. The general working model might be that inositol phosphatases would degrade the Ins(1,4,5)P3 or phosphoinositides, subsequently resulting in altering Ca2+ release, abscisic acid (ABA) signaling, vesicle trafficking or other cellular processes.