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1.
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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2.
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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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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4.
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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5.
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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Effectiveness of myoinositol for polycystic ovary syndrome: a systematic review and meta-analysis.
Zeng, L, Yang, K
Endocrine. 2018;(1):30-38
Abstract
PURPOSE To assess the effectiveness and safety of myoinositol for patients with PCOS. METHODS In this meta-analysis, data from randomized controlled trials are obtained to assess the effects of myoinositol vs. placebo or western medicine in women with PCOS. The study's registration number is CRD42017064563. The primary outcomes included total testosterone, estradiol (E2) and the homeostatic model assessment (HOMA) of insulin resistance. RESULT Ten trials involving 573 patients were included. The meta-analysis results show that: compared with the control group, myoinositol may improve HOMA index (WMD -0.65; 95% CI -1.02, -0.28; P = 0. 0005) and increase the E2 level (WMD 16.16; 95% CI 2.01, 30.31; P = 0. 03); while there is no enough strong evidence that the myoinositol has an effect on the total testosterone level (WMD -16.11; 95% CI -46.08, 13.86; P = 0. 29). CONCLUSION Based on current evidence, myoinositol may be recommended for the treatment of PCOS with insulin resistance, as well as for improving symptoms caused by decreased estrogen in PCOS.
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8.
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.
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Myo-inositol as a male fertility molecule: speed them up!
Condorelli, RA, La Vignera, S, Mongioì, LM, Vitale, SG, Laganà, AS, Cimino, L, Calogero, AE
European review for medical and pharmacological sciences. 2017;(2 Suppl):30-35
Abstract
Myo-inositol (MYO) usually represents a therapeutic option for female infertility associated with insulin resistance. Recently, several evidences are accumulating about the potential use of MYO for the treatment of male infertility. This article summarizes the rationale for MYO in the treatment of male infertility. In particular, it illustrates the potential antioxidant and prokinetic role of MYO, and its importance for the modulation of hormonal regulation. In the final part of the manuscript has been added a proposal for a clinical algorithm reserved for patients with asthenozoospermia, where probably MYO could exert specific pharmacological effects.