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BackgroundThe neurobiology of treatment-resistant schizophrenia (TRS) is poorly understood, and meta-analytic consensus regarding magnetic resonance spectroscopic profiles of glutamate, choline-containing compounds, myo-inositol, and other metabolites in the condition is lacking.MethodsIn this meta-analysis, we examined published findings for N-acetylaspartate, choline-containing compounds (phosphocholine+glycerophosphocholine), myo-inositol, creatine+phosphocreatine, glutamate, and glutamate+glutamine in the anterior cingulate cortex and dorsal striatum in people with TRS versus non-TRS as well as TRS versus healthy control participants (HCs) and TRS versus ultra TRS (i.e., TRS with clozapine resistance). A MEDLINE search revealed 9 articles including 239 people with pooled TRS and ultra TRS, 59 with ultra TRS, 175 with non-TRS, and 153 (HCs) that met meta-analytic criteria.ResultsSignificant effects included higher anterior cingulate cortex phosphocholine+glycerophosphocholine and myo-inositol in the pooled TRS and ultra TRS group than in both the non-TRS group and HCs as well as higher dorsal striatal phosphocholine+glycerophosphocholine in ultra TRS versus HCs, but no differences in other regional metabolites.ConclusionsThe observed metabolite profile in TRS (higher phosphocholine+glycerophosphocholine and myo-inositol signal) is consistent with the hypothesis that TRS has a neuroinflammatory component, although this meta-analysis is not a critical test of that hypothesis. A similar profile is seen in healthy aging, which is known to involve increased neuroinflammation and glial activation. Because the overall number of datasets was low, however, results should be considered preliminary and highlight the need for additional studies of brain metabolites in TRS and their possible association with inflammatory processes.

Myo-inositol plays a key role in the vasculature and may be beneficial for preventing harmful environmental effects. In this study aortic rings were isolated from middle-aged (12-month-old) male Wistar rats and preincubated with myo-inositol (0.01–100 mg/L) for 2 h. A stable thromboxane A2 analog was added (0.1 nM, 2 h) to analyze vascular dysfunction. The concentration of myo-inositol in the organ baths was determined via gas chromatography. In another experiment, human blood plasma was subjected to pro-oxidant - hydrogen peroxide administration, and myo-inositol was added to analyze lipid and protein oxidation processes. The thromboplastin time, prothrombin time, and thrombin time were also studied. Myo-inositol administration protected thiol groups against oxidative stress, meanwhile decreased vascular contraction and potentiated vasodilation (concentrations 1–100 mg/L, but not ≤ 0.1 mg/L), and changed the level of 8-isoprostane (concentrations: 0.1–100 mg/L, but not 0.01 mg/L) in plasma treated with H2O2/Fe2+. A dose above 100 mg/L additionally protected lipids (measured as thiobarbituric acid reactive substances) and increased thrombin time. Moreover, significant differences in vascular relaxation were observed between the studied myo-inositol concentrations (1 vs. 10 vs. 100 mg/L), which was not detected under the 0.1 mg/L. The concentration of myo-inositol in the organ baths determined via gas chromatography revealed that this nutraceutical agent was not used by the aortic rings during the incubation period in physiological processes. A protective effect of myo-inositol against prooxidant damage to human plasma and rat thoracic arteries has been demonstrated. [ABSTRACT FROM AUTHOR]

Considering the properties of myo-inositol (MI) and D-chiro-inositol (DCI), which are well known in polycystic ovary syndrome therapy, and the limitations of adult granulosa cell tumor (AGCT) treatment, especially for androgen-secreting tumors, we studied the role of MI and DCI in the androgen-rich environment of AGCTs. For this purpose, we analyzed the mRNA expression of steroidogenic genes and the secretion of progesterone (P4) and 17β-estradiol (E2) in an unstimulated and/or dihydrotestosterone (DHT)-stimulated environment under MI and DCI influence. Thus, we used the HGrC1 and KGN cell lines as in vitro models of healthy and cancerous granulosa cells. We found that DHT, the most potent androgen, increased E2 secretion and steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage gene (CYP11A1) mRNA expression without affecting 450 aromatase (CYP19A1) in AGCTs. However, after the MI and DCI treatment of KGN cells, both compounds strongly reduced StAR and CYP11A1 expression. Interestingly, in DHT-stimulated KGN cells, only DCI alone and its cotreatment with MI reduced both CYP11A1 mRNA and E2 secretion. These findings suggest that CYP11A1 is responsible for the antiestrogenic effect of DCI in the androgen-rich environment of AGCTs. Therefore, MI and DCI could be used as effective agents in the adjuvant treatment of AGCT, but further detailed studies are needed. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is the pivotal pathological hit in non‐alcoholic fatty liver disease (NAFLD). There is specific attention to combination/conjugated therapies for NAFLD management. As myo‐inositol (MI) has been shown to improve IR in animal and human trials, this study aimed to investigate the influence of MI supplementation on glycemic response and IR through AMPK/PI3K/AKT signaling pathway in obese patients with NAFLD. This double‐blinded placebo‐controlled randomized clinical trial was conducted on 48 obese (BMI = 30–40 kg/m2) patients with NAFLD who were randomly assigned to receiving either MI (4 g/day) or placebo (maltodextrin 4 g/day) group for 8 weeks. Before and after the trial, weight, height, serum glycemic parameters (inc. fasting glucose and insulin) as well as IR indices were assessed. Moreover, the mRNA expression levels of AMPK, AKT, and PDK‐1 in peripheral blood mononuclear cells (PBMCs) were determined. MI supplementation resulted in significant increases in the fold changes of AMPK, AKT, and PDK‐1 genes (p =.019, p =.049, and p =.029, respectively). Indeed, IR improved in terms of all IR indices in MI group (p <.05) after adjusting for the confounders, apart from quantitative insulin sensitivity check index (QUICKI). The results showed that MI supplementation not only upregulated AMPK, AKT, and PDK‐1 mRNA in PBMCs but also improved IR in obese patients with NAFLD. [ABSTRACT FROM AUTHOR]

• A non-human primate model of maternal immune activation (MIA) and neurodevelopment. • Offspring previously shown to have reduced frontal volumes and cognitive impairments. • Here, prefrontal n-acetylaspartate (NAA) is elevated across childhood and adolescence. • Elevated NAA correlates with less impaired cognition in these male MIA offspring. • Elevated prefrontal NAA may reflect a resilience-related process in MIA offspring. Converging data show that exposure to maternal immune activation (MIA) in utero alters brain development in animals and increases the risk of neurodevelopmental disorders in humans. A recently developed non-human primate MIA model affords opportunities for studies with uniquely strong translational relevance to human neurodevelopment. The current longitudinal study used 1H-MRS to investigate the developmental trajectory of prefrontal cortex metabolites in male rhesus monkey offspring of dams (n = 14) exposed to a modified form of the inflammatory viral mimic, polyinosinic:polycytidylic acid (Poly IC), in the late first trimester. Brain metabolites in these animals were compared to offspring of dams that received saline (n = 10) or no injection (n = 4). N-acetylaspartate (NAA), glutamate, creatine, choline, myo-inositol, taurine, and glutathione were estimated from PRESS and MEGA-PRESS acquisitions obtained at 6, 12, 24, 36, and 45 months of age. Prior investigations of this cohort reported reduced frontal cortical gray and white matter and subtle cognitive impairments in MIA offspring. We hypothesized that the MIA-induced neurodevelopmental changes would extend to abnormal brain metabolite levels, which would be associated with the observed cognitive impairments. Prefrontal NAA was significantly higher in the MIA offspring across all ages (p < 0.001) and was associated with better performance on the two cognitive measures most sensitive to impairment in the MIA animals (both p < 0.05). Myo-inositol was significantly lower across all ages in MIA offspring but was not associated with cognitive performance. Taurine was elevated in MIA offspring at 36 and 45 months. Glutathione did not differ between groups. MIA exposure in male non-human primates is associated with altered prefrontal cortex metabolites during childhood and adolescence. A positive association between elevated NAA and cognitive performance suggests the hypothesis that elevated NAA throughout these developmental stages reflects a protective or resilience-related process in MIA-exposed offspring. The potential relevance of these findings to human neurodevelopmental disorders is discussed. [ABSTRACT FROM AUTHOR]

Myo‐inositol may be efficient to improve sperm parameters to increase the chance of fertility. Although, the data are controversial. This study aimed to assess the impact of Myo‐inositol supplements on semen quality and in vitro fertilization (IVF) outcomes. In this systematic review and meta‐analysis, a comprehensive search was conducted in PubMed, Web of Science, and Embase. The objective was to identify relevant human studies that investigated the effects of Myo‐inositol treatment on various sperm factors, such as sperm motility, sperm concentration, sperm morphology, viable spermatozoa, spermatozoa with DNA fragmentation, and pregnancy rate. Additionally, the testosterone levels of patients with Oligo‐astheno‐teratozoospermia (OAT) after Myo‐inositol application were considered. The findings of 16 selected studies from 2240 citations indicated significant improvements in several parameters of sperm after Myo‐inositol administration. Myo‐inositol treatment was associated with a notable increase in total sperm motility (SMD 0.90; 95% CI: 0.34 to 1.46; I2 = 0%, p = .001) and progressive sperm motility (SMD 1.48; 95% CI: 0.37 to 2.59; I2  = 0%, p = .008). Additionally, there was a significant improvement in testosterone levels (SMD 0.54; 95% CI: 0.34 to 0.73; I2  = 0%, p < .0001). Furthermore, Myo‐inositol therapy demonstrated a significant decrease in spermatozoa with DNA fragmentation (SMD −1.37; 95% CI: −2.43 to −0.32; I2  = 85%, p = .01). This study suggests that Myo‐inositol therapy has a positive impact on specific sperm parameters, such as total and progressive sperm motility, along with testosterone levels. These findings provide support for the potential benefits of Myo‐inositol in improving male fertility parameters related to sperm factors. [ABSTRACT FROM AUTHOR]

Soil salinity is a worldwide problem threatening crop yields. Some plant growth‐promoting rhizobacteria (PGPR) could survive in high salt environment and assist plant adaptation to stress. Nevertheless, the genomic and metabolic features, as well as the regulatory mechanisms promoting salt tolerance in plants by these bacteria remain largely unknown. In the current work, a novel halotolerant PGPR strain, namely, Bacillus sp. strain RA can enhance tomato tolerance to salt stress. Comparative genomic analysis of strain RA with its closely related species indicated a high level of evolutionary plasticity exhibited by strain‐specific genes and evolutionary constraints driven by purifying selection, which facilitated its genomic adaptation to salt‐affected soils. The transcriptome further showed that strain RA could tolerate salt stress by balancing energy metabolism via the reprogramming of biosynthetic pathways. Plants exude a plethora of metabolites that can strongly influence plant fitness. The accumulation of myo‐inositol in leaves under salt stress was observed, leading to the promotion of plant growth triggered by Bacillus sp. strain RA. Importantly, myo‐inositol serves as a selective force in the assembly of the phyllosphere microbiome and the recruitment of plant‐beneficial species. It promotes destabilizing properties in phyllosphere bacterial co‐occurrence networks, but not in fungal networks. Furthermore, interdomain interactions between bacteria and fungi were strengthened by myo‐inositol in response to salt stress. This work highlights the genetic adaptation of RA to salt‐affected soils and its ability to impact phyllosphere microorganisms through the adjustment of myo‐inositol metabolites, thereby imparting enduring resistance against salt stress in tomato. [ABSTRACT FROM AUTHOR]

Background and purpose: Traumatic brain injury (TBI) and its consequences remain great challenges for neurology. Consequences of TBI are associated with various alterations in the brain but little is known about long-term changes of epigenetic DNA methylation patterns. Moreover, nothing is known about potential treatments that can alter these epigenetic changes in beneficial ways. Therefore, we have examined myo-inositol (MI), which has positive effects on several pathological conditions. Methods: TBI was induced in mice by controlled cortical impact (CCI). One group of CCI animals received saline injections for two months (TBI+SAL), another CCI group received MI treatment (TBI+MI) for the same period and one group served as a sham-operated control. Mice were sacrificed 4 months after CCI and changes in DNA methylome and transcriptomes were examined. Results: For the first time we: (i) provide comprehensive map of long-term DNA methylation changes after CCI in the hippocampus; (ii) identify differences by methylation sites between the groups; (iii) characterize transcriptome changes; (iv) provide association between DNA methylation sites and gene expression. MI treatment is linked with upregulation of genes covering 33 biological processes, involved in immune response and inflammation. In support of these findings, we have shown that expression of BATF2, a transcription factor involved in immune-regulatory networks, is upregulated in the hippocampus of the TBI+MI group where the BATF2 gene is demethylated. Conclusion: TBI is followed by long-term epigenetic and transcriptomic changes in hippocampus. MI treatment has a significant effect on these processes by modulation of immune response and biological pathways of inflammation.

SUMMARY: Cassava is a crucial staple crop for smallholder farmers in tropical Asia and Sub‐Saharan Africa. Although high yield remains the top priority for farmers, the significance of nutritional values has increased in cassava breeding programs. A notable negative correlation between provitamin A and starch accumulation poses a significant challenge for breeding efforts. The negative correlation between starch and carotenoid levels in conventional and genetically modified cassava plants implies the absence of a direct genomic connection between the two traits. The competition among various carbon pathways seems to account for this relationship. In this study, we conducted a thorough analysis of 49 African cassava genotypes with varying levels of starch and provitamin A. Our goal was to identify factors contributing to differential starch accumulation. Considering carotenoid levels as a confounding factor in starch production, we found that yellow‐ and white‐fleshed storage roots did not differ significantly in most measured components of starch or de novo fatty acid biosynthesis. However, genes and metabolites associated with myo‐inositol synthesis and cell wall polymer production were substantially enriched in high provitamin A genotypes. These results indicate that yellow‐fleshed cultivars, in comparison to their white‐fleshed counterparts, direct more carbon toward the synthesis of raffinose and cell wall components. This finding is underlined by a significant rise in cell wall components measured within the 20 most contrasting genotypes for carotenoid levels. Our findings enhance the comprehension of the biosynthesis of starch and carotenoids in the storage roots of cassava. Significance Statement: The development of high‐yielding cassava varieties with high‐carotenoid contents is an important goal in breeding to improve the nutritional value of the crop. However, high‐starch and high‐carotenoid levels are often inversely correlated. By comparing transcript and metabolite profiles of high‐starch and high‐carotenoid cassava storage roots, we found that the typically lower starch levels in high‐carotenoid genotypes are associated with increased carbon allocation toward myo‐inositol and cell wall component pathways. [ABSTRACT FROM AUTHOR]

Androgen excess is a key feature of several clinical phenotypes of polycystic ovary syndrome (PCOS). However, the presence of FSH receptor (FSHR) and aromatase (CYP19A1) activity responses to physiological endocrine stimuli play a critical role in the pathogenesis of PCOS. Preliminary data suggest that myo-Inositol (myo-Ins) and D-Chiro-Inositol (D-Chiro-Ins) may reactivate CYP19A1 activity. We investigated the steroidogenic pathway of Theca (TCs) and Granulosa cells (GCs) in an experimental model of murine PCOS induced in CD1 mice exposed for 10 weeks to a continuous light regimen. The effect of treatment with different combinations of myo-Ins and D-Chiro-Ins on the expression of Fshr, androgenic, and estrogenic enzymes was analyzed by real-time PCR in isolated TCs and GCs and in ovaries isolated from healthy and PCOS mice. Myo-Ins and D-Chiro-Ins, at a ratio of 40:1 at pharmacological and physiological concentrations, positively modulate the steroidogenic activity of TCs and the expression of Cyp19a1 and Fshr in GCs. Moreover, in vivo, inositols (40:1 ratio) significantly increase Cyp19a1 and Fshr. These changes in gene expression are mirrored by modifications in hormone levels in the serum of treated animals. Myo-Ins and D-Chiro-Ins in the 40:1 formula efficiently rescued PCOS features by up-regulating aromatase and FSHR levels while down-regulating androgen excesses produced by TCs. [ABSTRACT FROM AUTHOR]

Background Prostate cancer remains the second most frequent diagnosed cancer in men and is the third leading cause of cancer related death, despite many available treatment options. The use of dietary supplements to prevent this cancer is one method of controlling it. Myo-inositol, a dietary component, has been shown to have cancer-chemopreventive properties against a variety of experimental cancers, however few research have been conducted, and molecular mechanisms are unclear. Methods In the current study, we investigated at the growth-inhibitory properties of myo-inositol and associated mechanisms in the androgen-independent human prostate cancer DU-145 cells.After 48 hours of treatment with myo-inositol, cytological studies using an inverted phase contrast microscope and Hoechst 33342/PI dual-staining assay revealed characteristic apoptotic morphology of cancer cells. MTT assay against mouse lung fibroblast (L929) cell line and trypan blue dye exclusion assay against human prostate cancer (DU-145) cells were used to determine cytotoxic efficacy. Flow cytometry and FITC/PI labelling were used to confirm the presence of apoptosis. Results The growth inhibitory effect and the IC50 value were demonstrated by myo-inositol at 0.06 mg/ml (**p<0.05). It is suspected that cell deaths are related to apoptosis induction and cell-cycle arrest. Treatment with Myo-inositol has been further identified by induction of early and late apoptosis (***p<0.01). Apoptosis can also be detected using DNA fragmentation and Hoechst 33342 fluorescent dye stain analysis. Myo-inositol caused an alteration to the cell cycle regulation on DU-145 cell line at G0/G1 and S phase, respectively (***p<0.01). Conclusion These molecular and cytometric alterations shed light on how myo-inositol produces statically significant growth inhibition, G1-S phase arrest, and late apoptotic cell death in human prostate cancer DU145 cells. [ABSTRACT FROM AUTHOR]

Maize (Zea mays L.) is an important food crop with a wide range of uses in both industry and agriculture. Drought stress during its growth cycle can greatly reduce maize crop yield and quality. However, the molecular mechanisms underlying maize responses to drought stress remain unclear. In this work, a WRKY transcription factor‐encoding gene, ZmWRKY30, from drought‐treated maize leaves was screened out and characterized. ZmWRKY30 gene expression was induced by dehydration treatments. The ZmWRKY30 protein localized to the nucleus and displayed transactivation activity in yeast. Compared with wild‐type (WT) plants, Arabidopsis lines overexpressing ZmWRKY30 exhibited a significantly enhanced drought stress tolerance, as evidenced by the improved survival rate, increased antioxidant enzyme activity by superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), elevated proline content, and reduced lipid peroxidation recorded after drought stress treatment. In contrast, the mutator (Mu)‐interrupted ZmWRKY30 homozygous mutant (zmwrky30) was more sensitive to drought stress than its null segregant (NS), characterized by the decreased survival rate, reduced antioxidant enzyme activity (SOD, POD, and CAT) and proline content, as well as increased malondialdehyde accumulation. RNA‐Seq analysis further revealed that, under drought conditions, the knockout of the ZmWRKY30 gene in maize affected the expression of genes involved in reactive oxygen species (ROS), proline, and myo‐inositol metabolism. Meanwhile, the zmwrky30 mutant exhibited significant downregulation of myo‐inositol content in leaves under drought stress. Combined, our results suggest that ZmWRKY30 positively regulates maize responses to water scarcity. This work provides potential target genes for the breeding of drought‐tolerant maize. [ABSTRACT FROM AUTHOR]

Seawater (SW)-acclimated Nile tilapia, Oreochromis niloticus, reared under a salinity 30 environment had lower growth and survival than the freshwater (FW)-acclimated fish. It was hypothesized that cells of the SWacclimated fish had not been able to synthesize an adequate level of a compatible osmolyte, myo-inositol (MI), in adjusting to the salinity 30 environment. In this study, MI supplements, at 250, 500, and 750 mg/kg pellets, were provided to the fish through top-dressing. After the 30-day feeding trial, the following parameters were determined: final body weights; survival; biomass increase; feed conversion ratio (FCR); plasma osmolality and ions; and two transcripts in the gills mips250 and mipa1 encoding enzymes responsible for MI biosynthesis. The SW-acclimated O. niloticus receiving 500-mg MI supplement had significantly higher survival, biomass increase, and lower FCR than those of the SW-acclimated fish receiving no supplement. At 500-mg MI supplemental level, the increasing values of plasma osmolality and Na+ observed in SW-acclimated fish were significantly attenuated. The transcript mipa1, but not mips250, was markedly up-regulated in the SW-acclimated O. niloticus, compared with that of the FW-acclimated fish. Again, MI at 500-mg supplement attenuated the upregulation significantly. This study suggests that MI supplement at the optimum level enhanced the performance of SW-acclimated O. niloticus, and through yet unknown mechanisms, attenuated some of their physiological responses to the osmotic stress. [ABSTRACT FROM AUTHOR]

Introduction: Myo-inositol (MI) is the most abundant inositol found in nature. To date MI supplementation is reported to be effective in the treatment of polycystic ovary syndrome, it is also suggested to alleviate the symptoms of diabetes and neurodegenerative disorders, but to date no statistically significant effects of inositol on depressive and anxiety symptoms were proven. In the study of anxiolytic effects in zebrafish, we often use the thigmotaxis index measuring the ratio of the amount of time the animal spends near the walls compared to the entire arena. Aim: The objective of this paper was to examine the effect of MI on zebrafish embryos’ locomotor activity, as well as its potential anxiolytic activity in zebrafish larvae. Material and methods: In the first part of the experiment, the embryos were incubated with 5, 10, 20, and 40 mg/mL MI. 1-day post fertilization, embryo mobility was evaluated and burst activity was calculated. In the next part of the study, the behavior of 5-day-old larvae was tested. Results: Tests on embryo movement showed an increase in burst activity in the MI group at concentrations of 40 mg/mL (p < 0.0001) and a slight decrease in the group at concentrations of 10 mg/mL (p < 0.05). MI in the light/dark challenge had no impact on the thigmotaxis index. Conclusions: MI was shown to not affect stress reduction in zebrafish larvae. Further research on the potential of MI and other stereoisomers is needed. [ABSTRACT FROM AUTHOR]

The main objective of this work was to evaluate the application of individual and ensemble machine learning models to classify malignant and benign breast masses using features from two-dimensional (2D) correlated spectroscopy spectra extracted from five-dimensional echo-planar correlated spectroscopic imaging (5D EP-COSI) and diffusion-weighted imaging (DWI). Twenty-four different metabolite and lipid ratios with respect to diagonal fat peaks (1.4 ppm, 5.4 ppm) from 2D spectra, and water and fat peaks (4.7 ppm, 1.4 ppm) from one-dimensional non-water-suppressed (NWS) spectra were used as the features. Additionally, water fraction, fat fraction and water-to-fat ratios from NWS spectra and apparent diffusion coefficients (ADC) from DWI were included. The nine most important features were identified using recursive feature elimination, sequential forward selection and correlation analysis. XGBoost (AUC: 93.0%, Accuracy: 85.7%, F1-score: 88.9%, Precision: 88.2%, Sensitivity: 90.4%, Specificity: 84.6%) and GradientBoost (AUC: 94.3%, Accuracy: 89.3%, F1-score: 90.7%, Precision: 87.9%, Sensitivity: 94.2%, Specificity: 83.4%) were the best-performing models. Conventional biomarkers like choline, myo-Inositol, and glycine were statistically significant predictors. Key features contributing to the classification were ADC, 2D diagonal peaks at 0.9 ppm, 2.1 ppm, 3.5 ppm, and 5.4 ppm, cross peaks between 1.4 and 0.9 ppm, 4.3 and 4.1 ppm, 2.3 and 1.6 ppm, and the triglyceryl-fat cross peak. The results highlight the contribution of the 2D spectral peaks to the model, and they demonstrate the potential of 5D EP-COSI for early breast cancer detection.

BackgroundAlthough proton magnetic resonance spectroscopy (MRS) has been used to study metabolite alterations in stimulant (methamphetamine and cocaine) substance use disorders (SUDs) for over 25 years, data-driven consensus regarding the nature and magnitude of these alterations is lacking.MethodIn this meta-analysis, we examined associations between SUD and regional metabolites (N-acetyl aspartate (NAA), choline, myo-inositol, creatine, glutamate, and glutamate+glutamine (glx)) in the medial prefrontal cortex (mPFC), frontal white matter (FWM), occipital cortex, and basal ganglia as measured by 1 H-MRS. We also examined moderating effects of MRS acquisition parameters (echo time (TE), field strength), data quality (coefficient of variation (COV)), and demographic/clinical variables.ResultsA MEDLINE search revealed 28 articles that met meta-analytic criteria. Significant effects included lower mPFC NAA, higher mPFC myo-inositol, and lower mPFC creatine in SUD relative to people without SUD. mPFC NAA effects were moderated by TE, with larger effects at longer TEs. For choline, although no group effects were observed, effect sizes in the mPFC were related to MRS technical indicators (field strength, COV). No effects of age, sex, primary drug of use (methamphetamine vs. cocaine), duration of use, or duration of abstinence were observed. Evidence for moderating effects of TE and COV may have implications for future MRS studies in SUDs.ConclusionsThe observed metabolite profile in methamphetamine and cocaine SUD (lower NAA and creatine with higher myo-inositol) parallels that observed in Alzheimer's disease and mild cognitive impairment, suggesting these drugs are associated with neurometabolic differences similar to those characterizing these neurodegenerative conditions.

Background: Polycystic ovarian syndrome (PCOS) is an endocrinological disease of women of the reproductive age group. The study aimed to compare the efficacy of Myo-inositol and folic acid with and without D-chiro-inositol in the improvement of symptoms of PCOS within 4 months for the evaluation of the most effective therapeutic regimen. Methods: This Quasi-experimental study was conducted at Gynecology & Obstetrics OPD of two Private Healthcare Hospitals in Sialkot from February 2024-June 2024. The Rotterdam criteria (2003) was used for diagnosis of PCOS in non-pregnant women aged between 18-35 years. A total of 90 PCOS patients (45 in each group) were enrolled using a purposive sampling technique and distributed into two treatment groups. Group A received MI 2000 mg + DCI 50 mg + FA 200 mcg while Group B received MI 2000 mg + FA 200 mcg BD, after meal, for 17-18 weeks. Patients’ menstrual cycle history, BMI, transabdominal-ultrasonographic picture, and serum total testosterone levels were evaluated at Day 0, 60, and 120 to compare these measurements before and after initiation of treatment. SPSS was used to analyze the data. Independent samples t-test and Repeated measures ANOVA were used to analyze the data. P-value ≤ 0.05 was considered statistically significant. Results: After the intervention, body mass index (kg/m²), serum total testosterone levels (ng/dl), and follicular number per ovary decreased, with Group A demonstrating better performance with p-values 0.03, 0.04, and < 0.001 respectively. Both groups exhibited increased follicular size in both ovaries and decreased ovarian volumes. By Day 120, menstrual cycle regularity was more pronounced in Group A than in Group B (1.00 ± 0.00 and 1.13 ± 0.34 respectively, p-value

Myo-inositol (MI) is a crucial constituent of the cell membrane and has a pivotal role to play in transmembrane signal transduction, ion channel regulation, and cell transport. Fish skin is a vital mucosal immune organ, and there are few studies that have examined the effect of MI on fish skin.Therefore, the purpose of this study was to investigate the role of dietary MI in regulating the skin immune response of grass carp (Ctenopharyngodon idella). A total of 540 fish (221.33 ± 0.84 g) were fed six diets containing graded levels of MI (27.0, 137.9, 286.8, 438.6, 587.7, and 737.3 mg/kg) for 10 weeks. When the growth test was complete, a 14-day challenge was conducted with Aeromonas hydrophila in each group. Our results indicated that the most effective MI concentrations (approximately 438.6–737.3 mg/kg diet) resulted in the following outcomes: (1) MI reduced the morbidity of grass carp skin and increased the thickness of the dense dermis layer. (2) MI enhanced the physical barrier function of the skin, maybe via increasing antioxidant capacity, inhibiting apoptosis, and improving tight junction-related signaling pathways (nuclear factor erythroid 2-related factor 2, p38 mitogen-activated protein kinase, and myosin light chain kinase). (3) MI enhanced skin immune barrier function, possibly via regulating anti-inflammatory and pro-inflammatory cytokines, as well as the target of rapamycin (TOR) and nuclear factor kappa B (NFκB) pathways. This study led to the following conclusion based on its findings: the MI supplementation strengthened the fish skin barrier function and protected it against Aeromonas hydrophila. The dietary MI requirement in on-growing grass carp was estimated to be 370.90 mg/kg by a broken-line method analysis of skin morbidity.

This study investigates the effects of inositol (INO) supplementation on cardiac changes caused by Li in mice. The study involved 4 groups of C57BL6 mice (n=10 each): (i) mice orally administered with Li2CO3 for 8 weeks, then 4 additional weeks without (Li_group) or (ii) with INO supplementation (Li_INOdelayed_group) (total of 12 weeks); (iii) mice given Li2CO3 and INO supplementation concurrently for 12 weeks (Li+INO_group); (iv) one group left untreated (C–group). The INO was administered as a mixture of myo-inositol and d-chiro-inositol (80:1) in drinking water. The mice were characterised for heart morphology, function, electrical activity, arrhythmogenic susceptibility, and multiorgan histopathology (heart, liver and kidney). Cardiomyocyte size, protein expression of key signalling pathways related to hypertrophy, and transcription levels of ion channel subunits and hypertrophy markers were evaluated in the ventricle tissue. The study found that INO supplementation reduced the Li-induced cardiac adverse effects, including systolic impairment and increased susceptibility to arrhythmias. The positive effect on arrhythmias might be attributed to the restored expression levels of the potassium channel subunit Kv 1.5. Additionally, INO improved cardiomyocyte hypertrophy, possibly by inhibiting the Li-induced activation of the ERK1/2 signalling pathway and by restoring the normal expression level of BNP, and alleviated injury in the liver and kidney. The effect was preventive if INO supplementation was taken concurrently with Li and therapeutic if INO was administered after Li-induced cardiac impairments were established. These results provide new insights into the cardioprotective effect of INO and suggest a potential treatment approach for Li-induced cardiac disease.

Summary: Background: The metabolic environment plays a crucial role in the development of heart failure (HF). Our prior research demonstrated that myo-inositol, a metabolite transported by the sodium-myo-inositol co-transporter 1 (SMIT-1), can induce oxidative stress and may be detrimental to heart function. However, plasmatic myo-inositol concentration has not been comprehensively assessed in large cohorts of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Methods: Plasmatic myo-inositol levels were measured using mass spectrometry and correlated with clinical characteristics in no HF subjects and patients with HFrEF and HFpEF from Belgian (male, no HF, 53%; HFrEF, 84% and HFpEF, 40%) and Canadian cohorts (male, no HF, 51%; HFrEF, 92% and HFpEF, 62%). Findings: Myo-inositol levels were significantly elevated in patients with HF, with a more pronounced increase observed in the HFpEF population of both cohorts. After adjusting for age, sex, body mass index, hypertension, diabetes, and atrial fibrillation, we observed that both HFpEF status and impaired kidney function were associated with elevated plasma myo-inositol. Unlike HFrEF, abnormally high myo-inositol (≥69.8 μM) was linked to unfavourable clinical outcomes (hazard ratio, 1.62; 95% confidence interval, [1.05–2.5]) in patients with HFpEF. These elevated levels were correlated with NTproBNP, troponin, and cardiac fibrosis in this subset of patients. Interpretation: Myo-inositol is a metabolite elevated in patients with HF and strongly correlated to kidney failure. In patients with HFpEF, high myo-inositol levels predict poor clinical outcomes and are linked to markers of cardiac adverse remodelling. This suggests that myo-inositol and its transporter SMIT1 may have a role in the pathophysiology of HFpEF. Funding: BECAME-HF was supported by Collaborative Bilateral Research Program Québec – Wallonie-Brussels Federation.

Hygromycin A is a broad-spectrum antibiotic that contains a furanose, cinnamic acid, and aminocyclitol moieties. The biosynthesis of the aminocyclitol has been proposed to proceed through six enzymatic steps from glucose 6-phosphate through myo-inositol to the final methylenedioxy-containing aminocyclitol. Although there is some in vivo evidence for this proposed pathway, biochemical support for the individual enzyme activities is lacking. In this study, we verify the activity for one enzyme in this pathway. We show that Hyg17 is a myo-inositol dehydrogenase that has a unique substrate scope when compared to other myo-inositol dehydrogenases. Furthermore, we analyze sequences from the protein family containing Hyg17 and discuss genome mining strategies that target this protein family to identify biosynthetic clusters for natural product discovery.

Pregnancy is a critical period marked by intricate physiological changes and maintaining maternal and fetal well-being is paramount. Inositols, a group of naturally occurring sugar alcohols, have gained attention for their potential benefits during pregnancy. This abstract provides a comprehensive review of the current literature on using inositols, primarily myo-inositol (MI) and D-chiro-inositol (DCI) in pregnancy. Inositols are crucial in cellular signal transduction and insulin sensitivity, making them integral to various physiological processes. Several studies suggest that inositols may contribute to preventing and managing gestational diabetes mellitus (GDM). MI, in particular, has shown promise in improving insulin sensitivity and mitigating insulin resistance, thereby influencing glucose metabolism. As our understanding of inositol’s role in pregnancy deepens, it may emerge as a valuable supplement to enhance maternal and fetal health outcomes.

BackgroundMyo-inositol (or inositol) and its derivatives not only function as important metabolites for multiple cellular processes but also act as co-factors and second messengers in signaling pathways. Although inositol supplementation has been widely studied in various clinical trials, little is known about its effect on idiopathic pulmonary fibrosis (IPF). Recent studies have demonstrated that IPF lung fibroblasts display arginine dependency due to loss of argininosuccinate synthase 1 (ASS1). However, the metabolic mechanisms underlying ASS1 deficiency and its functional consequence in fibrogenic processes are yet to be elucidated.MethodsMetabolites extracted from primary lung fibroblasts with different ASS1 status were subjected to untargeted metabolomics analysis. An association of ASS1 deficiency with inositol and its signaling in lung fibroblasts was assessed using molecular biology assays. The therapeutic potential of inositol supplementation in fibroblast phenotypes and lung fibrosis was evaluated in cell-based studies and a bleomycin animal model, respectively.ResultsOur metabolomics studies showed that ASS1-deficient lung fibroblasts derived from IPF patients had significantly altered inositol phosphate metabolism. We observed that decreased inositol-4-monophosphate abundance and increased inositol abundance were associated with ASS1 expression in fibroblasts. Furthermore, genetic knockdown of ASS1 expression in primary normal lung fibroblasts led to the activation of inositol-mediated signalosomes, including EGFR and PKC signaling. Treatment with inositol significantly downregulated ASS1 deficiency-mediated signaling pathways and reduced cell invasiveness in IPF lung fibroblasts. Notably, inositol supplementation also mitigated bleomycin-induced fibrotic lesions and collagen deposition in mice.ConclusionThese findings taken together demonstrate a novel function of inositol in fibrometabolism and pulmonary fibrosis. Our study provides new evidence for the antifibrotic activity of this metabolite and suggests that inositol supplementation may be a promising therapeutic strategy for IPF.

The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) and the browning of white AT (WAT) are promising targets for combating weight gain. Nutritional factors during prenatal and early postnatal stages can influence the development of AT, affecting the likelihood of obesity later on. This narrative review focuses on the nutritional programming of AT features. Research conducted across various animal models with diverse interventions has provided insights into the effects of specific compounds on AT development and function, influencing the development of crucial structures and neuroendocrine circuits responsible for energy balance. The hormone leptin has been identified as an essential nutrient during lactation for healthy metabolic programming against obesity development in adults. Studies have also highlighted that maternal supplementation with polyunsaturated fatty acids (PUFAs), vitamin A, nicotinamide riboside, and polyphenols during pregnancy and lactation, as well as offspring supplementation with myo-inositol, vitamin A, nicotinamide riboside, and resveratrol during the suckling period, can impact AT features and long-term health outcomes and help understand predisposition to obesity later in life. [ABSTRACT FROM AUTHOR]

In this study, a new micro delivery system based on an anionic methacrylate copolymer, able to improve the biological response of myo-inositol by daily oral administration, was manufactured by spray-drying. It has an ideal dose form for oral administration, with an experimental drug loading (DL)% of 14% and a regulated particle size of less than 15 µm. The new formulation features an improvement on traditional formulations used as a chronic therapy for the treatment of polycystic ovary syndrome. The microparticles' release profile was studied and ex vivo porcine intestinal mucosa permeation experiments were performed to predict potential improvements in oral absorption. Batch n. 3, with the higher Eudragit/MI weight ratio (ratio = 6), showed the best-modified release profiles of the active ingredient, ensuring the lowest myo-inositol loss in an acidic environment. The in vivo evaluation of the myo-inositol micro delivery system was carried out in a rat animal model to demonstrate that the bioavailability of myo-inositol was increased when compared to the administration of the same dosage of the pure active ingredient. The AUC and Cmax of the loaded active molecule in the micro delivery system was improved by a minimum of 1.5 times when compared with the pure substance, administered with same dosage and route. Finally, the increase of myo-inositol levels in the ovary follicles was assessed to confirm that a daily administration of the new formulation improves myo-inositol concentration at the site of action, resulting in an improvement of about 1.25 times for the single administration and 1.66 times after 7 days of repeated administration when compared to pure MI. [ABSTRACT FROM AUTHOR]

Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic β cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients. [ABSTRACT FROM AUTHOR]

Introduction and purpose Polycystic ovary syndrome is a common reproductive disorder, accompanied primarily by hyperandrogenism and insulin resistance. Myo-inositol (MI) and D-chiro-inositol (DCI), have emerged as potential therapeutic agents due to their role as insulin sensitizers. This article examines the effects of inositol therapy on fertility in women with PCOS and its role in assisted reproductive technology (ART). Studies suggest that inositols alleviate irregular menstruation, reduce androgen levels and positively affect ovulation rates. MI supplementation has also shown positive effects during controlled ovarian hyperstimulation and IVF procedures, reducing the required FSH dose and cycle length. However, despite positive results on ovulation and menstrual regularity, the article indicates the need for further studies to establish inositol as standard ART therapy in patients with PCOS. Material and methods The following review was based on articles from the PubMed and Google Scholar databases. Key search terms included polycystic ovary syndrome; assisted reproductive treatment, insulin resistance, inositols, Myo-inositol, D-chiro-inositol. Conclusions Inositols are a promising therapeutic option for women with PCOS. They have been shown to have positive effects on improving insulin sensitivity and fertility. However, despite inositol's safety and easy availability, the ideal dose and timing of use, the appropriate MI/DCI ratio, as well as the potential side effects of excess DCI and the problem of inositol resistance, require further comprehensive studies. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hormonal changes physiologically occurring in menopausal women may increase the risk of developing metabolic and vasomotor disturbances, which contribute to increase the risk of developing other concomitant pathologies, such as metabolic syndrome (MetS). Materials and Methods: Retrospective data from 200 menopausal women with MetS and vasomotor symptoms taking one sachet per day of the dietary supplement INOFOLIC® NRT (Farmares srl, Rome, Italy) were collected. Each sachet consisted of myo-Inositol (2000 mg), cocoa polyphenols (30 mg), and soy isoflavones (80 mg, of which 50 mg is genistin). Patients recorded their symptoms through a medical questionnaire at the beginning of the administration (T0) and after 6 months (T1). Results: We observed an improvement in both the frequency and the severity of hot flushes: increased percentage of 2–3 hot flushes (28 at T0 vs. 65% at T1, p value < 0.001) and decreased percentage of 4–9 hot flushes (54% at T0 vs. 18% at T1, p value < 0.001). Moreover, symptoms of depression improved after supplementation (87% at T0 vs. 56% at T1 of patients reported moderate depression symptoms, p value < 0.001). Regarding metabolic profile, women improved body mass index and waist circumference with a reduction in the percentage of overweight and obesity women (88% at T0 vs. 51% at T1, p value = 0.01; 14% at T0 vs. 9% at T1, p value = 0.04). In addition, the number of women suffering from non-insulin dependent diabetes reduced (26% at T0 vs. 16% at T1, p value = 0.04). Conclusions: These data corroborate previously observed beneficial effects of the oral administration of myo-Inositol, cocoa polyphenols, and soy isoflavones against menopausal symptoms in the study population. Considering the promising results of the present study, further prospective controlled clinical trials are needed to deeply understand and support the efficacy of these natural compounds for the management of menopausal symptoms. [ABSTRACT FROM AUTHOR]

myo‐inositol, a naturally occurring cyclic hexaol, was converted into conformationally constrained diols 4 bearing two adamantane‐like components in the molecule. For the synthesis of 4, an orthoester derivative of myo‐inositol bearing an adamantane‐like rigid structure on which three hydroxyl groups were attached was used as the precursor. Two molecules of the orthoester were tethered via acetalization using two axially oriented hydroxyl groups, successfully constructing the core structure of 4. Polyaddition of 4 with diisocyanate was performed to obtain the corresponding polyurethanes, with glass transition temperatures (Tg) ranging from 150 to 210°C. [ABSTRACT FROM AUTHOR]

Setting: Insulin resistance (IR) and compensatory hyperinsulinemia are considered contributing factors toward polycystic ovary syndrome (PCOS). Objectives: This study evaluates the frequency of metabolic abnormalities in PCOS patients and the effects of myo-inositol (MI) and D-chiro-inositol (DCI), in a 40:1 ratio on hormonal and metabolic parameters. Participants: Thirty-four women with PCOS phenotype A (endocrine-metabolic syndrome [EMS-type 1]) between the ages of 20–40. Design: Open prospective study with phenotype A (EMS-type I, n = 34) supplemented with 2,255 mg/day of inositol (MI and DCI in a 40:1 ratio) for 3 months. Methods: The following were measured before and after treatment: serum levels of follicular stimulating hormone, luteinizing hormone (LH), estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), anti-Müllerian hormone, glucose, insulin, HOMA-IR, and body mass index (BMI). Results: 55.9% of the enrolled patients were overweight or obese, 50% affected by IR, 17.6% with a history of gestational diabetes mellitus, and 61.8% had familial diabetes mellitus. At the conclusion of the study, BMI (p = 0.0029), HOMA-IR (p < 0.001) significantly decreased, along with decreased numbers of patients with elevated insulin levels. The supplementation resulted in decreased total testosterone (p < 0.001), free testosterone (p < 0.001), FAI (p < 0.001), and LH (p < 0.001); increased SHBG (p < 0.001) and estradiol (p < 0.001). Limitations: The present analysis was limited to a 12-week follow-up, which precluded a long-term evaluation of the effects of MI and DCI combination. Also, this period was insufficient to achieve and analyze clinical changes such as restoration of the menstrual cycle, restoration of reproductive function, and clinical manifestations of hyperandrogenism. Conclusions: Supplementation improved metabolic and hormonal profile in PCOS phenotype A (EMS-type I) patients. This builds upon previous work that demonstrated that combined inositol treatment may be effective in PCOS. The study presented herein, used a reduced concentration than in prior literature; however, a significant change in hormonal and metabolic parameters was still observed. [ABSTRACT FROM AUTHOR]

The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy (1H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)) was also performed in a subset of subjects during clamp. In dataset A, 48 participants were studied during fasting with brain 1H-MRS, while in dataset B 21 participants underwent paired brain 1H-MRS acquisitions under fasting and clamp conditions. In dataset C 16 subjects underwent brain 18F-FDG-PET and 1H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity. [ABSTRACT FROM AUTHOR]

Mandibular retrognathism occurs by insufficient mandibular growth and causes several issues, such as respiratory difficulty and diminished masticatory function. At present, functional orthodontic appliances are used for stimulating mandibular growth in pediatric cases. However, the effectiveness of functional appliances is not always stable in daily practices. A more effective, reliable, and safer therapeutic method for mandibular growth promotion would be helpful for growing mandibular retrognathism patients. As we previously discovered that nutritional supplementation of myo-inositol in growing mice specifically increases mandibular endochondral growth, we performed preclinical animal experiments in rabbits in this study. Briefly, six-week-old male Japanese white rabbits were fed with or without myo-inositol supplementation in laboratory chow until 25 weeks old, and 3D image analysis using micro CT data and histological examinations was done. Myo-inositol had no systemic effect, such as femur length, though myo-inositol specifically augmented the mandibular growth. Myo-inositol increased the thickness of mandibular condylar cartilage. We discovered that the nutritional supplementation of myo-inositol during the growth period specifically augmented mandibular growth without any systemic influence, even in rabbits. Our results suggest the possibility of clinical use of myo-inositol for augmentation of the mandibular growth in growing mandibular retrognathism patients in the future. [ABSTRACT FROM AUTHOR]

BackgroundIn an era of precision and stratified medicine, homogeneity in population-based cohorts, stringent causative entry, and pattern analysis of datasets are key elements to investigate medical treatments. Adhering to these principles, we collected in vivo and in vitro data pointing to an insulin-sensitizing/insulin-mimetic effect of myo-inositol (MYO) relevant to cell regeneration in dentistry and oral surgery. Confirmation of this possibility was obtained by in silico analysis of the relation between in vivo and in vitro results (the so-called bed-to-benchside reverse translational approach).ResultsFourteen subjects over the 266 screened were young adult, normal weight, euglycemic, sedentary males having normal appetite, free diet, with a regular three-times-a-day eating schedule, standard dental hygiene, and negligible malocclusion/enamel defects. Occlusal caries were detected by fluorescence videoscanning, whereas body composition and energy balance were estimated with plicometry, predictive equations, and handgrip. Statistically significant correlations (Pearson r coefficient) were found between the number of occlusal caries and anthropometric indexes predicting insulin resistance (IR) in relation to the abdominal/visceral fat mass, fat-free mass, muscular strength, and energy expenditure adjusted to the fat and muscle stores. This indicated a role for IR in affecting dentin reparative processes. Consistently, in vitro administration of MYO to HUVEC and Swiss NIH3T3 cells in concentrations corresponding to those administered in vivo to reduce IR resulted in statistically significant cell replication (ANOVA/Turkey tests), suggesting that MYO has the potential to counteract inhibitory effects of IR on dental vascular and stromal cells turnover. Finally, in in silico experiments, quantitative evaluation (WOE and information value) of a bioinformatic Clinical Outcome Pathway confirmed that in vitro trophic effects of MYO could be transferred in vivo with high predictability, providing robust credence of its efficacy for oral health.ConclusionOur reverse bed-to-benchside data indicate that MYO might antagonize the detrimental effects of IR on tooth decay. This provides feasibility for clinical studies on MYO as a regenerative factor in dentistry and oral surgery, including dysmetabolic/aging conditions, bone reconstruction in oral destructive/necrotic disorders, dental implants, and for empowering the efficacy of a number of tissue engineering methodologies in dentistry and oral surgery.

Objective: Recent studies have shown that gene alternative splicing (AS) and long noncoding RNAs (lncRNAs) are involved in diabetes mellitus (DM) and its complications. Currently, myo-inositol (MI) is considered as effective for the treatment of insulin resistance and lipid metabolism disorders in diabetes patients. We hope to better explore the potential roles of gene AS and lncRNAs in liver glucose and lipid metabolism in diabetes, as well as the effects of myo-inositol treatment, through transcriptome analysis. Methods: This study analysed glucose and lipid metabolism-related biochemical indicators and liver HE staining in four groups of mice: the control group (Ctrl group), the diabetes group (DM group), the myo-inositol treatment group (MI group), and the metformin treatment group (Met group). The changes in relevant gene-regulated alternative splicing events (RASEs) and lncRNAs were analysed by RNA sequencing of liver tissue, and coexpression analysis and functional enrichment analysis were used to predict the possible lncRNAs and RASEs involved in liver glucose and lipid metabolism. Result: Metformin and myo-inositol alleviated insulin resistance, lipid metabolism disorders, and hepatic steatosis in diabetic mice. Transcriptome sequencing analysis revealed differential splicing events of genes related to lipid metabolism and differentially expressed lncRNAs (DElncRNAs). Six different lncRNAs and their potentially interacting splicing events were predicted. Conclusion: The present study revealed novel changes in RASEs and lncRNAs in the livers of diabetic mice following treatment with myo-inositol, which may shed light on the potential mechanisms by which myo-inositol delays and treats the progression of hepatic glucose and lipid metabolism in diabetes.

ObjectivesThis study aimed at developing dictionary learning (DL) based compressed sensing (CS) reconstruction for randomly undersampled five-dimensional (5D) MR Spectroscopic Imaging (3D spatial + 2D spectral) data acquired in prostate cancer patients and healthy controls, and test its feasibility at 8x and 12x undersampling factors.Materials and methodsProspectively undersampled 5D echo-planar J-resolved spectroscopic imaging (EP-JRESI) data were acquired in nine prostate cancer (PCa) patients and three healthy males. The 5D EP-JRESI data were reconstructed using DL and compared with gradient sparsity-based Total Variation (TV) and Perona-Malik (PM) methods. A hybrid reconstruction technique, Dictionary Learning-Total Variation (DLTV), was also designed to further improve the quality of reconstructed spectra.ResultsThe CS reconstruction of prospectively undersampled (8x and 12x) 5D EP-JRESI data acquired in prostate cancer and healthy subjects were performed using DL, DLTV, TV and PM. It is evident that the hybrid DLTV method can unambiguously resolve 2D J-resolved peaks including myo-inositol, citrate, creatine, spermine and choline.ConclusionImproved reconstruction of the accelerated 5D EP-JRESI data was observed using the hybrid DLTV. Accelerated acquisition of in vivo 5D data with as low as 8.33% samples (12x) corresponds to a total scan time of 14 min as opposed to a fully sampled scan that needs a total duration of 2.4 h (TR = 1.2 s, 32 [Formula: see text]×16 [Formula: see text]×8 [Formula: see text], 512 [Formula: see text] and 64 [Formula: see text]).

d-Glucaric acid is a potential biobased platform chemical. Previously mainly Escherichia coli, but also the yeast Saccharomyces cerevisiae, and Pichia pastoris, have been engineered for conversion of d-glucose to d-glucaric acid via myo-inositol. One reason for low yields from the yeast strains is the strong flux towards glycolysis. Thus, to decrease the flux of d-glucose to biomass, and to increase d-glucaric acid yield, the four step d-glucaric acid pathway was introduced into a phosphoglucose isomerase deficient (Pgi1p-deficient) Saccharomyces cerevisiae strain. High d-glucose concentrations are toxic to the Pgi1p-deficient strains, so various feeding strategies and use of polymeric substrates were studied. Uniformly labelled 13C-glucose confirmed conversion of d-glucose to d-glucaric acid. In batch bioreactor cultures with pulsed d-fructose and ethanol provision 1.3 g d-glucaric acid L−1 was produced. The d-glucaric acid titer (0.71 g d-glucaric acid L−1) was lower in nitrogen limited conditions, but the yield, 0.23 g d-glucaric acid [g d-glucose consumed]−1, was among the highest that has so far been reported from yeast. Accumulation of myo-inositol indicated that myo-inositol oxygenase activity was limiting, and that there would be potential to even higher yield. The Pgi1p-deficiency in S. cerevisiae provides an approach that in combination with other reported modifications and bioprocess strategies would promote the development of high yield d-glucaric acid yeast strains. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a multisystem reproductive–metabolic disorder and the most common endocrine cause of infertility. The objective of our study was to determine the influence of myo-inositol (MI) on insulin resistance (IR), menstrual cycle regularity, and hyperandrogenism in women suffering from PCOS with normal BMI and diagnosed IR. Methods: We performed a prospective randomized controlled trial (RCT) that included 60 participants with PCOS who had IR and a normal BMI. Two groups were formed. A group of thirty patients received MI, and thirty patients in the control group received metformin (MET). Results: A statistically significant reduction in the area under the curve (AUC) of insulin values during the oral glucose tolerance test (OGTT) was recorded in both examined groups after the applied therapy with MI and MET. The regularity of the menstrual cycle in both groups was improved in >90% of patients. A statistically significant decrease in androgenic hormones (testosterone, SHBG, free androgen index—FAI, androstenedione) was recorded in both groups and did not differ between the groups. Conclusions: Both MI and MET can be considered very effective in the regulation of IR, menstrual cycle irregularities, and hyperandrogenism in women with PCOS. [ABSTRACT FROM AUTHOR]

Recently, we showed that patients with knee osteoarthritis (KOA) demonstrate alterations in the thalamic concentrations of several metabolites compared with healthy controls: higher myo-inositol (mIns), lower N-acetylaspartate (NAA), and lower choline (Cho). Here, we evaluated whether these metabolite alterations are specific to KOA or could also be observed in patients with a different musculoskeletal condition, such as chronic low back pain (cLBP). Thirty-six patients with cLBP and 20 healthy controls were scanned using 1H-magnetic resonance spectroscopy (MRS) and a PRESS (Point RESolved Spectroscopy) sequence with voxel placement in the left thalamus. Compared with healthy controls, patients with cLBP demonstrated lower absolute concentrations of NAA (P = 0.0005) and Cho (P < 0.05) and higher absolute concentrations of mIns (P = 0.01) when controlling for age, as predicted by our previous work in KOA. In contrast to our KOA study, mIns levels in this population did not significantly correlate with pain measures (eg, pain severity or duration). However, exploratory analyses revealed that NAA levels in patients were negatively correlated with the severity of sleep disturbance (P < 0.01), which was higher in patients compared with healthy controls (P < 0.001). Additionally, also in patients, both Cho and mIns levels were positively correlated with age (P < 0.01 and P < 0.05, respectively). Altogether, these results suggest that thalamic metabolite changes may be common across etiologically different musculoskeletal chronic pain conditions, including cLBP and KOA, and may relate to symptoms often comorbid with chronic pain, such as sleep disturbance. The functional and clinical significance of these brain changes remains to be fully understood. [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy (MRS) is the primary method that can measure the levels of metabolites in the brain in vivo. To achieve its potential in clinical usage, the reliability of the measurement requires further articulation. Although there are many studies that investigate the reliability of gamma‐aminobutyric acid (GABA), comparatively few studies have investigated the reliability of other brain metabolites, such as glutamate (Glu), N‐acetyl‐aspartate (NAA), creatine (Cr), phosphocreatine (PCr), or myo‐inositol (mI), which all play a significant role in brain development and functions. In addition, previous studies which predominately used only two measurements (two data points) failed to provide the details of the time effect (e.g., time‐of‐day) on MRS measurement within subjects. Therefore, in this study, MRS data located in the anterior cingulate cortex (ACC) were repeatedly recorded across 1 year leading to at least 25 sessions for each subject with the aim of exploring the variability of other metabolites by using the index coefficient of variability (CV); the smaller the CV, the more reliable the measurements. We found that the metabolites of NAA, tNAA, and tCr showed the smallest CVs (between 1.43% and 4.90%), and the metabolites of Glu, Glx, mI, and tCho showed modest CVs (between 4.26% and 7.89%). Furthermore, we found that the concentration reference of the ratio to water results in smaller CVs compared to the ratio to tCr. In addition, we did not find any time‐of‐day effect on the MRS measurements. Collectively, the results of this study indicate that the MRS measurement is reasonably reliable in quantifying the levels of metabolites. [ABSTRACT FROM AUTHOR]

Inositols are insulin-sensitizing compounds that have also regulatory functions in human reproduction. In the ovary, myo-inositol (myo-ins) mediates the granulosa response to follicle-stimulating hormone stimuli and plays a crucial role in determining oocyte maturation. D-chiro-inositol, by contrast, is involved in the regulation of ovarian steroidogenesis and at high concentrations may be detrimental for oocyte quality due to its aromatase down-modulator activity. Supplementation with myo-ins during assisted reproductive technologies reduces the total amount of gonadotropins used in polycystic ovary syndrome (PCOS) and non-PCOS women and leads to improvements in oocyte quality and maturation and embryo development and an increase in the rate of successful pregnancies. Myo-ins also acts directly on spermatogenesis, improving sperm performance in vitro and in vivo. Inositols are insulin-sensitizing compounds of promising efficacy in the management of polycystic ovary syndrome (PCOS). On the one hand, myo-inositol (myo-ins) plays a regulatory role in male and female reproductive function, influencing the development of oocytes, spermatozoa, and embryos. On the other hand, high concentrations of D-chiro-inositol (D-chiro-ins) in the ovary may adversely affect oocyte quality. This review analyses the available literature, which encourages the clinical use of myo-ins in assisted reproductive technologies (ARTs) due to its beneficial effects on female and male reproduction. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and lipid alterations. Besides pharmacological treatment, lifestyle modifications and nutraceuticals can be used to manage glucose and lipid profiles, which is crucial for preventing, or avoiding, serious consequences associated with the condition. This randomized controlled clinical trial on 75 patients with T2DM evaluated the effects of a combination of myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc on glucose and lipid profile. The intention-to-treat analysis displayed no significant differences in glucose parameters between the groups; however, the study group displayed reduced levels of total cholesterol (p = 0.01) and LDL (p = 0.03) after 3 months of supplementation. A subgroup analysis involving patients who did not modify their antidiabetic therapy, after 6 months displayed improved levels of total cholesterol (p = 0.03) and LDL (p = 0.04) in the study group versus placebo, along with a greater body weight reduction (p = 0.03) after 3 months. Furthermore, within the study group, levels of HDL (p = 0.03) and triglycerides (p = 0.04) improved after 3 months. These findings support supplementation with myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc as an adjuvant and safe strategy to manage the lipid profiles of patients with T2DM. [ABSTRACT FROM AUTHOR]

Salinity poses a significant threat to plant growth through induction of osmotic and ionic stress and disruption of nutrient absorption. Biostimulants derived from agricultural waste offer a sustainable solution to alleviate salt-induced damage to plants and contribute to a circular and sustainable economy. In this study, we applied a combination of myo-inositol and corn steep liquor from waste sources to seedling cabbage (Brassica rapa subsp. pekinensis) and investigated their effects on plant growth under NaCl-simulated salt stress. Different concentrations of myo-inositol and corn steep liquor were applied to the roots, revealing that 150 mM NaCl significantly inhibited the growth and physiological metabolism of cabbage seedlings. Substrate application of myo-inositol, corn steep liquor, and their combination materials increased biomass, photosynthetic pigments, soluble sugars, soluble proteins, and the contents of K+, Ca2+, and Mg2+ in cabbage under salt stress conditions, while reducing malondialdehyde, electrolyte leakage, Na+ content, and the ratios of Na+/K+, Na+/Ca2+, and Na+/Mg2+. Therefore, root application of myo-inositol, corn steep liquor, and myo-inositol–corn steep liquor combination materials enhanced photosynthesis and enhanced cabbage salt stress resistance by maintaining cell osmotic and ion balance. The most pronounced positive effects were observed in the treatment with 0.1 mL L−1 corn steep liquor +288 mg L−1 myo-inositol. This study provides a theoretical basis and technical guidance for the combined utilization of myo-inositol and corn steep liquor to boost early growth and salt resistance in crops. [ABSTRACT FROM AUTHOR]

Assisted reproductive techniques can help many infertile couples conceive. Therefore, there is a need for an effective method to overcome the widespread problems of infertile men and women. Oocyte and sperm quality can increase the chances of successful in vitro fertilisation. The maturation environment in which gametes are present can affect their competency for fertilisation. It is well established that myo-inositol (MI) plays a pivotal role in reproductive physiology. It participates in cell membrane formation, lipid synthesis, cell proliferation, cardiac regulation, metabolic alterations, and fertility. This molecule also acts as a direct messenger of insulin and improves glucose uptake in various reproductive tissues. Evidence suggests that MI regulates events such as gamete maturation, fertilisation, and embryo growth through intracellular Ca2 + release and various signalling pathways. In addition to the in-vivo production of MI from glucose in the reproductive organs, its synthesis by in vitro-cultured sperm and follicles has also been reported. Therefore, MI is suggested as a therapeutic approach to maintain sperm and oocyte health in men and women with reproductive disorders and individuals of reproductive age. [ABSTRACT FROM AUTHOR]

• Myo-inositol synthesizes several biochemical components in living systems. • L- myo -inositol-1-phosphate synthase is the principal enzyme for myo-inositol biosynthesis. • Myo-inositol derivatives influence abiotic stress tolerance in plants. • The activity of the rate limiting enzyme is higher in desiccation tolerant bryophytes. L- myo -inositol-1-phosphate synthase (MIPS) and its product, free myo- inositol have been isolated from different bryophytes. MIPS was purified for the first time from the moss, Sphagnum junghuhnianum to 58.67 fold over its homogenate fraction with about 32.86 % recovery. D-glucose-6-phosphate was the exclusive substrate of the enzyme without which there was no enzyme activity and the deduction of NH 4 Cl, ME and NAD+ substantially reduced the activity of the enzyme. The K m for D-glucose-6-phosphate and NAD+were 1.81 mM and 0.25 mM, while the V max for the same were 1.42 mM and 1.12 mM respectively. The molecular weight of the enzyme was assessed to be approximately 174 kDa. The activity of the enzyme increased with the increase in the duration of incubation time for up to 90 min and with the increase in protein concentration for up to 300 µg. The pH and temperature maxima were pH 7.0 and at 30 °C, respectively, but a significant activity was observed at 10 °C also. NH 4 Cl substantially stimulated the enzyme activity while K + and Ca2+ also raised the activity slightly. Li+ greatly inhibited the activity. Inhibitory activity was also shown by Cd2+, Mn2+, Zn2+and Hg2+ of which Hg2+ showed the maximum inhibition. Interestingly, the Sphagnum junghuhnianum MIPS showed the characteristics of both Class-II and Class-III aldolase. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to determine whether neurometabolite abnormalities indicating neuroinflammation and neuronal injury are detectable in individuals post–coronavirus disease 2019 (COVID-19) with persistent neuropsychiatric symptoms. Methods All participants were studied with proton magnetic resonance spectroscopy at 3 T to assess neurometabolite concentrations (point-resolved spectroscopy, relaxation time/echo time = 3000/30 ms) in frontal white matter (FWM) and anterior cingulate cortex–gray matter (ACC-GM). Participants also completed the National Institutes of Health Toolbox cognition and motor batteries and selected modules from the Patient-Reported Outcomes Measurement Information System. Results Fifty-four participants were evaluated: 29 post–COVID-19 (mean ± SD age, 42.4 ± 12.3 years; approximately 8 months from COVID-19 diagnosis; 19 women) and 25 controls (age, 44.1 ± 12.3 years; 14 women). When compared with controls, the post–COVID-19 group had lower total N-acetyl compounds (tNAA; ACC-GM: −5.0%, P =.015; FWM: –4.4%, P =.13), FWM glutamate + glutamine (–9.5%, P =.001), and ACC-GM myo-inositol (−6.2%, P =.024). Additionally, only hospitalized patients post–COVID-19 showed age-related increases in myo-inositol, choline compounds, and total creatine (interaction P =.029 to <.001). Across all participants, lower FWM tNAA and higher ACC-GM myo-inositol predicted poorer performance on several cognitive measures (P =.001–.009), while lower ACC-GM tNAA predicted lower endurance on the 2-minute walk (P =.005). Conclusions In participants post–COVID-19 with persistent neuropsychiatric symptoms, the lower-than-normal tNAA and glutamate + glutamine indicate neuronal injury, while the lower-than-normal myo-inositol reflects glial dysfunction, possibly related to mitochondrial dysfunction and oxidative stress in Post-COVID participants with persistent neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Objective: Polycystic Ovary Syndrome is the most prevalent hormonal disorder in females. Over the years, metformin (MET) has become the first-line choice of treatment; however, due to its gastrointestinal side effects, a more recent drug, myo-inositol (MI), has been introduced. We aim to conduct a systematic review and meta-analysis to compare the effects of MET and MI on hormonal and metabolic parameters. Materials and methods: Authors extensively searched PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science for randomized clinical trials (RCTs) until August 2021. Eight (n = 8) articles were included, with a total sample size of 1088, of which 460 patients received MET, 436 received MI, and 192 received a combination of both. Standard mean differences (SMDs) and Confidence Intervals (CIs) were used for data synthesis, and forest plots were made using Review Manager 5.4 for Statistical Analysis using the random-effect model. Results: The meta-analysis indicates that there is no significant difference between MET and MI in terms of their effects on BMI (SMD = 0.16, 95% CI: − 0.11 to 0.43, p = 0.24), fasting insulin (SMD = 0.00, 95% CI: − 0.26 to 0.27, p = 0.97), fasting blood sugar (SMD = 0.11, 95% CI: − 0.31to 0.53, p = 0.60), HOMA index (SMD = 0.09, 95% CI: − 0.20 to 0.39, p = 0.50), and LH/FSH (SMD = 0.20, 95% CI: − 0.24 to 0.64, p = 0.37). BMI, fasting blood sugar, and LH/FSH ratio reported moderate heterogeneity because of the varying number of study participants. Conclusion: Our meta-analysis comparing hormonal and metabolic parameters between MET and MI did not show much significant difference, indicating both drugs are equally beneficial in improving metabolic and hormonal parameters in patients with PCOS. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is closely associated with higher risks of atherosclerosis through a number of molecular cascades such as the sirtuin-1 (SIRT-1) pathway. Myo-inositol as a precursor isomer of cyclohexanehexols exerts anti-hyperlipidemic and anti-obesity features in metabolic disorders. The current study aimed to assess the effects of myo-inositol supplementation on genes expression of the SIRT-1 pathway, atherogenic indices, and hematological parameters in obese patients with NAFLD. Methods: This double-blinded randomized clinical trial was conducted on 44 obese patients with ultrasound proven- NAFLD who received dietary recommendations and were randomly allocated into either myo-inositol (4 g/day) or placebo (maltodextrin 4 g/day) receiving groups for 8 weeks. At baseline and the end of the study mRNA expression levels of SIRT-1 pathway genes in peripheral blood mononuclear cells (PBMCs), complete blood cell count, lipid profile, and atherogenic indices were assessed. Inter-group differences were determined using analysis of covariance (by adjusting for the potential confounders) at the end of the trial. Results: At the end of the trial mRNA expression levels of low-density- lipoprotein receptor (LDLR) (only in myo-inositol group) and endothelial nitric oxide synthase (eNOS) (in both groups) significantly increased, compared with steady-state levels (p = 0.004 and p = 0.001, respectively). Moreover, myo-inositol supplementation significantly inhibited lectin-like oxidized- low-density lipoprotein receptor-1 (LOX-1) expression compared with the placebo group (p = 0.045). Slight improvements in Cholesterol-related atherogenic indices and hematological parameters were also observed in myo-inositol group, compared with baseline values (p