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1.
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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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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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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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 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.
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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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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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The effects of inositol supplementation on lipid profiles among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials.
Tabrizi, R, Ostadmohammadi, V, Lankarani, KB, Peymani, P, Akbari, M, Kolahdooz, F, Asemi, Z
Lipids in health and disease. 2018;(1):123
Abstract
BACKGROUND Several studies have evaluated the effect of inositol supplementation on lipid profiles among population with metabolic diseases; however, the findings are controversial. This review of randomized controlled trials (RCTs) was performed to summarize the evidence of the effects of inositol supplementation on lipid profiles among population with metabolic diseases. METHODS Relevant RCTs studies were searched in Cochrane Library, EMBASE, MEDLINE, and Web of Science until October 2017. Two researchers assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies, independently. To check for the heterogeneity among included studies Q-test and I2 statistics were used. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as summary of the effect size. RESULTS Overall, 14 RCTs were included into meta-analysis. Pooled results showed that inositol supplementation among patients with metabolic diseases significantly decreased triglycerides (SMD - 1.24; 95% CI, - 1.84, - 0.64; P < 0.001), total- (SMD - 1.09; 95% CI, - 1.83, - 0.55; P < 0.001), and LDL-cholesterol levels (SMD - 1.31; 95% CI, - 2.23, - 0.39; P = 0.005). There was no effect of inositol supplementation on HDL-cholesterol levels (SMD 0.20; 95% CI, - 0.27, 0.67; P = 0.40). CONCLUSIONS Inositol supplementation may result in reduction in triglycerides, total- and LDL-cholesterol levels, but did not affect HDL-cholesterol levels among patients with metabolic diseases. Additional prospective studies regarding the effect of inositol supplementation on lipid profiles in patients with metabolic diseases are necessary.
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9.
Prion propagation and inositol polyphosphates.
Wickner, RB, Edskes, HK, Bezsonov, EE, Son, M, Ducatez, M
Current genetics. 2018;(3):571-574
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Abstract
The [PSI+] prion is a folded in-register parallel β-sheet amyloid (filamentous polymer) of Sup35p, a subunit of the translation termination factor. Our searches for anti-prion systems led to our finding that certain soluble inositol polyphosphates (IPs) are important for the propagation of the [PSI+] prion. The IPs affect a wide range of processes, including mRNA export, telomere length, phosphate and polyphosphate metabolism, energy regulation, transcription and translation. We found that 5-diphosphoinositol tetra(or penta)kisphosphate or inositol hexakisphosphate could support [PSI+] prion propagation, and 1-diphosphoinositol pentakisphosphate appears to inhibit the process.
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Application of genetically encoded redox biosensors to measure dynamic changes in the glutathione, bacillithiol and mycothiol redox potentials in pathogenic bacteria.
Tung, QN, Linzner, N, Loi, VV, Antelmann, H
Free radical biology & medicine. 2018;:84-96
Abstract
Gram-negative bacteria utilize glutathione (GSH) as their major LMW thiol. However, most Gram-positive bacteria do not encode enzymes for GSH biosynthesis and produce instead alternative LMW thiols, such as bacillithiol (BSH) and mycothiol (MSH). BSH is utilized by Firmicutes and MSH is the major LMW thiol of Actinomycetes. LMW thiols are required to maintain the reduced state of the cytoplasm, but are also involved in virulence mechanisms in human pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, Streptococcus pneumoniae, Salmonella enterica subsp. Typhimurium and Listeria monocytogenes. Infection conditions often cause perturbations of the intrabacterial redox balance in pathogens, which is further affected under antibiotics treatments. During the last years, novel glutaredoxin-fused roGFP2 biosensors have been engineered in many eukaryotic organisms, including parasites, yeast, plants and human cells for dynamic live-imaging of the GSH redox potential in different compartments. Likewise bacterial roGFP2-based biosensors are now available to measure the dynamic changes in the GSH, BSH and MSH redox potentials in model and pathogenic Gram-negative and Gram-positive bacteria. In this review, we present an overview of novel functions of the bacterial LMW thiols GSH, MSH and BSH in pathogenic bacteria in virulence regulation. Moreover, recent results about the application of genetically encoded redox biosensors are summarized to study the mechanisms of host-pathogen interactions, persistence and antibiotics resistance. In particularly, we highlight recent biosensor results on the redox changes in the intracellular food-borne pathogen Salmonella Typhimurium as well as in the Gram-positive pathogens S. aureus and M. tuberculosis during infection conditions and under antibiotics treatments. These studies established a link between ROS and antibiotics resistance with the intracellular LMW thiol-redox potential. Future applications should be directed to compare the redox potentials among different clinical isolates of these pathogens in relation to their antibiotics resistance and to screen for new ROS-producing drugs as promising strategy to combat antimicrobial resistance.