Search

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.

Cataract is one of the most prevalent protein aggregation disorders and still the most common cause of vision loss worldwide. The metabolically quiescent core region of the human lens lacks cellular or protein turnover; it has therefore evolved remarkable mechanisms to resist light-scattering protein aggregation for a lifetime. We now report that one such mechanism involves an unusually abundant lens metabolite, myo- inositol, suppressing aggregation of lens crystallins. We quantified aggregation suppression using our previously well-characterized in vitro aggregation assays of oxidation-mimicking human γD-crystallin variants and investigated myo- inositol's molecular mechanism of action using solution NMR, negative-stain TEM, differential scanning fluorometry, thermal scanning Raman spectroscopy, turbidimetry in redox buffers, and free thiol quantitation. Unlike many known chemical chaperones, myo -inositol's primary target was not the native, unfolded, or final aggregated states of the protein; rather, we propose that it was the rate-limiting bimolecular step on the aggregation pathway. Given recent metabolomic evidence that it is severely depleted in human cataractous lenses compared to age-matched controls, we suggest that maintaining or restoring healthy levels of myo- inositol in the lens may be a simple, safe, and globally accessible strategy to prevent or delay lens opacification due to age-onset cataract., Competing Interests: ES, SC, CW, DT, NW, AM, RK, ES No competing interests declared, (© 2022, Serebryany et al.)

Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Ab-positive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain lesions in 11 MS and 4 AQP4Ab-NMOSD patients using an optimised MRS methodology at ultra-high field strength (7T) incorporating correction for T2 water relaxation differences between lesioned and normal tissue. MS metabolite results were in keeping with the existing literature: total N-acetylaspartate (NAA) was lower in lesions compared to normal appearing brain white matter (NAWM) with reciprocal findings for myo-Inositol. An unexpected subtlety revealed by our technique was that total NAA differences were likely driven by NAA-glutamate (NAAG), a ubiquitous CNS molecule with functions quite distinct from NAA though commonly quantified together with NAA in MRS studies as total NAA. Surprisingly, AQP4Ab-NMOSD showed no significant differences for total NAA, NAA, NAAG or myo-Inositol between lesion and NAWM sites, nor were there any differences between MS and AQP4Ab-NMOSD for a priori hypotheses. Post-hoc testing revealed a significant correlation between NAWM Ins:NAA and disability (as measured by EDSS) for disease groups combined, driven by the AP4Ab-NMOSD group. Utilising an optimised MRS methodology, our study highlights some under-explored subtleties in MRS profiles, such as the absence of myo-Inositol concentration differences in AQP4Ab-NMOSD brain lesions versus NAWM and the potential influence of NAAG differences between lesions and normal appearing white matter in MS., Competing Interests: Declaration of Competing Interest GT reported no declarations of interest.; YK reported no declarations of interest.; RM reported no declarations of interest.; SM reported receiving travel grants from Biogen, Novartis, Bayer, Merck & Co, Roche, and Almirall and honorarium from Biogen for advisory work.; AW reported no declarations of interest.; AC reported no declarations of interest.; RE reported no declarations of interest.; GDL is supported by the NIHR Biomedical Research Centre (BRC), Oxford and has research funding from the Oxford BRC, MRC(UK), UK MS Society, and National Health and Medical Research (Australia). GD has received travel expenses from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, American Academy of Neurology, and MS Academy, and honoraria as an invited speaker for Novartis, American Academy of Neurology, and MS Academy.; AW reported no declarations of interest.; MC reported no declarations of interest.; IT reported no declarations of interest.; JP reported no declarations of interest.; CS reported no declarations of interest.; UE reported no declarations of interest., (Copyright © 2021. Published by Elsevier Inc.)

Glutamate is an important neurotransmitter. Although many studies have measured glutamate concentration in vivo using magnetic resonance spectroscopy (MRS), researchers have not reached a consensus on the accuracy of glutamate quantification at the field strength of 3 T. Besides, there is not an optimal MRS protocol for glutamate measurement. In this work, both simulation and phantom scans indicate that glutamate can be estimated with reasonable accuracy (<10% error on average) using the standard Point-RESolved Spectroscopy (PRESS) technique with TE 30 ms; glutamine, however, is likely underestimated, which is also suggested by results from human scans using the same protocol. The phantom results show an underestimation of glutamate and glutamine for PRESS with long TE and MEGA-PRESS off-resonance spectra. Despite the underestimation, there is a high correlation between the measured values and the true values (r > 0.8). Our results suggest that the quantification of glutamate and glutamine is reliable but can be off by a scaling factor, depending on the imaging technique. The outputs from all three PRESS sequences (TE = 30, 68 and 80 ms) are also highly correlated with each other (r > 0.7) and moderately correlated (r > 0.5) with the results from the MEGA-PRESS difference spectra with moderate to good shimming (linewidth < 16 Hz)., (© 2020 John Wiley & Sons, Ltd.)

Background/objectives: Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels., Methods: Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks' gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed., Results: Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted β [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [-21.2, 183.2], AAT = 0.8 ml [-8.4, 10.0])., Conclusions: High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.

The dissipation and residue of validamycin A in grapes were investigated under field conditions. An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of validamycin A in grapes was established and validated. Methanol and water (90/10, v / v ) were used for validamycin A extraction and purification used MCX solid-phase extraction cartridges. The average recoveries of validamycin A in grapes at 0.01, 0.50, and 5.0 mg/kg levels were between 83.8 and 91.4%, with relative standard deviations of 2.3-3.0%. The half-lives of validamycin A in grape were 4.4-6.1 days. The terminal residues in grapes over a range of harvest times (7, 14, and 21 days) were no more than 0.73 mg/kg. According to Chinese consumption data, the risk quotient (RQ) of validamycin A was 3.22%, demonstrating a low risk to consumers. The current study may offer guidance for validamycin A use and could aid the government in determining the maximum residue level (MRL) values for validamycin A in grapes.

Previous studies support that myo- and D-chiro-inositol isomers are promising bioactives for the treatment of women with polycystic ovary syndrome and for lowering the risk of gestational diabetes mellitus in pregnant women, whereas scyllo-inositol may have some benefits for neurological disorders (e.g., Alzheimer's disease). Though potentially useful to better understand inositol isomer metabolism and study their role in health and disease, routine analysis of inositol isomers in plasma and urine with a single analytical method is not yet feasible due to the lack of a suitable analytical assay. To address this, we developed and validated a robust ultra-high-performance-liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the quantification of inositol isomers in plasma and urine. This method resolves seven inositol isomers with accurate quantification of total chiro- (D and L enantiomers), myo-, and scyllo-inositols and is semi-quantitative for neo-inositol. For urine and plasma myo-inositol, the method repeatability and intermediate reproducibility were below 6% and 8%, respectively. Then, for both chiro- and scyllo-inositols, repeatability and intermediate reproducibility were below 10% and 14%, respectively. A pilot study was carried out to quantify and compare the pattern of inositol isomers in urine and plasma of non-pregnant and pregnant women and showed for the first time that urinary myo- and scyllo-inositol concentrations were significantly higher for women in the third trimester of pregnancy compared with non-pregnant women. These findings warrant further research to understand the biological significance of the observed differences in inositol profiles and suggest a potential role of scyllo-inositol.Graphical abstract Plasma and urinary inositol isomer profiles measured by UHPLC-MS/MS reveal differences in scyllo-inositol levels between non-pregnant and pregnant women.

A microwave-assisted extraction (MAE) method was developed for the extraction of bioactive inositols (D-chiro- and myo-inositols) from lettuce (Lactuca sativa) leaves as a strategy for the revalorization of these agrofood residues. Gas chromatography-mass spectrometry was selected for the simultaneous determination of inositols and sugars (glucose, fructose, and sucrose) in these samples. A Box-Behnken experimental design was used to maximize the extraction of inositols based on the results of single factor tests. Optimal conditions of the extraction process were as follows: liquid-to-solid ratio of 100:1 v/w, 40°C, 30 min extraction time, 20:80 ethanol:water (v/v), and one extraction cycle. When compared with conventional solid-liquid extraction (SLE), MAE was found to be more effective for the extraction of target bioactive carbohydrates (MAE 5.42 mg/g dry sample versus SLE 4.01 mg/g dry sample). Then, MAE methodology was applied to the extraction of inositols from L. sativa leaves of different varieties (var. longifolia, var. capitata and var. crispa). D-chiro- and myo-inositol contents varied between 0.57-7.15 and 0.83-3.48 mg/g dry sample, respectively. Interfering sugars were removed from the extracts using a biotechnological procedure based on the use of Saccharomyces cerevisiae for 24 h. The developed methodology was a good alternative to classical procedures to obtain extracts enriched in inositols from lettuce residues, which could be of interest for the agrofood industry., (© 2020 Wiley-VCH GmbH.)

Winter provides many challenges for terrestrial arthropods, including low temperatures and decreased food availability. Most arthropods are dormant in the winter and resume activity when conditions are favorable, but a select few species remain active during winter. Winter activity is thought to provide a head start on spring growth and reproduction, but few studies have explicitly tested this idea or investigated tradeoffs associated with winter activity. Here, we detail biochemical changes in overwintering winter-active wolf spiders, Schizocosa stridulans, to test the hypothesis that winter activity promotes growth and energy balance. We also quantified levels of putative cryoprotectants throughout winter to test the prediction that winter activity is incompatible with biochemical adaptations for coping with extreme cold. Body mass of juveniles increased 3.5-fold across winter, providing empirical evidence that winter activity promotes growth and therefore advancement of spring reproduction. While spiders maintained protein content throughout most of the winter, lipid content decreased steadily, suggesting either a lack of available prey to maintain lipids, or more likely, an allometric shift in body composition as spiders grew larger. Carbohydrate content showed no clear seasonal trend but also tended to be higher at the beginning of the winter. Finally, we tested the hypothesis that winter activity is incompatible with cryoprotectant accumulation. However, we observed accumulation of glycerol, myo-inositol, and several other cryoprotectants, although levels were lower than those typically observed in overwintering arthropods. Together, our results indicate that winter-active wolf spiders grow during the winter, and while cryoprotectant accumulation was observed in the winter, the modest levels relative to other species could make them susceptible to extreme winter events., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Mechanisms of pruritus are implicated in the dysregulation of the metabolites in the spinal cord. We investigated pruritus behavioral testing in three groups of young adult male C57Bl/6 mice, including one group treated with normal saline, while the other groups intradermally injected with α-Me-5-HT (histamine-independent pruritogen), compound 48/80 (histamine-dependent pruritogen) at the nape skin of the neck, respectively. Proton nuclear magnetic resonance spectroscopy (MRS) was used to compare spinal metabolites from the vertebral cervical among three groups, and to study the association of spinal metabolite ratio and pruritus intensity. The MRS-measured N-acetylaspartate-to-myoinositol ratio (NAA/Ins) was significantly correlated with the number of scratches between normal saline group and 48/80 group or α-Me-5-HT group (both P<0.0001), indicating that NAA/Ins may be a robust surrogate marker of histamine-independent/dependent pruritogen. There was significant difference in Glu/Ins between normal saline group and 48/80 group (P=0.017), indicating that Glu/Ins may be a surrogate marker of histamine-dependent pruritogen, while GABA/Ins was highly significantly different between normal saline group and α-Me-5-HT group (P=0.008), suggesting that GABA/Ins may be a surrogate marker of histamine-independent pruritogen. MRS may reflect the extent of pruritus intensity elicited by α-Me-5-HT and compound 48/80 with sensitivity similar to the number of scratches, and above potential markers need to be further validated in pre-clinical and clinical treatment trials.

A combination of electrochemistry (EC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry ( off-line EC-MALDI-TOF-MS) was applied for determination of the studied biologically active compounds (D-glucose, D-fructose, D-galactose, D-pinitol, L- chiro -inositol, and myo -inositol) and their possible electrochemical metabolites. In this work, boron-doped diamond electrode (BDD) was used as a working electrode. MALDI-TOF-MS experiments were carried out (both in positive and negative ion modes and using two matrices) to identify the structures of electrochemical products. This was one of the first applications of the EC system for the generation of electrochemical products produced from saccharides and cyclitols. Moreover, exploratory data analysis approaches (correlation networks, hierarchical cluster analysis, weighted plots) were used in order to present differences/similarities between the obtained spectra, regarding the class of analyzed compounds, ionization modes, and used matrices. This work presents the investigation and comparison of fragmentation patterns of sugars, cyclitols, and their respective products generated through the electrochemistry (EC) process.

Influence of atmosphere and storage period on the physicochemical and biological properties of harvested vegetable soybeans stored for 10 d at 25 °C was investigated. Storing vegetable soybeans under modified atmosphere (low O 2 and high CO 2 ), was more effective in maintaining its green color and mass than storing them under normoxia. Principal component 1 (PC1; contribution rate: 25%) was related to the atmospheres, whereas PC2 (contribution rate: 19%) was related to storage period. Cluster analysis showed that some types of sugars decreased, whereas some types of organic and amino acids increased with deterioration. Alanine, an indicator of low O 2 stress, was maintained for 3 d under modified atmospheres, whereas alanine significantly decreased under normoxia. The concentrations of inositol and niacinamide (functional ingredients) under the modified atmospheres were significantly higher than those under normoxia. Thus, storage under modified atmospheres was effective in maintaining freshness and increasing the nutritional content of vegetable soybeans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Previous neuroimaging studies have detected markers of neuroinflammation in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Magnetic Resonance Spectroscopy (MRS) is suitable for measuring brain metabolites linked to inflammation, but has only been applied to discrete regions of interest in ME/CFS. We extended the MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain. Additionally, we tested whether MRS-derived brain temperature is elevated in ME/CFS patients. Fifteen women with ME/CFS and 15 age- and gender-matched healthy controls completed fatigue and mood symptom questionnaires and whole-brain echo-planar spectroscopic imaging (EPSI). Choline (CHO), myo-inositol (MI), lactate (LAC), and N-acetylaspartate (NAA) were quantified in 47 regions, expressed as ratios over creatine (CR), and compared between ME/CFS patients and controls using independent-samples t-tests. Brain temperature was similarly tested between groups. Significant between-group differences were detected in several regions, most notably elevated CHO/CR in the left anterior cingulate (p < 0.001). Metabolite ratios in seven regions were correlated with fatigue (p < 0.05). ME/CFS patients had increased temperature in the right insula, putamen, frontal cortex, thalamus, and the cerebellum (all p < 0.05), which was not attributable to increased body temperature or differences in cerebral perfusion. Brain temperature increases converged with elevated LAC/CR in the right insula, right thalamus, and cerebellum (all p < 0.05). We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed regions. Our findings may indicate that ME/CFS involves neuroinflammation.

Byproducts from artichoke represent the majority of the mass collected from the plant and constitute an interesting source of bioactive compounds such as inositols and caffeoylquinic acids. In this work, a microwave assisted extraction (MAE) methodology was developed for the simultaneous extraction of these compounds from artichoke stalks, leaves, receptacles and external bracts. Optimal MAE conditions to maximize the extraction of these bioactives and the antioxidant activity were 97 °C, 3 min, ethanol:water (50:50, v/v). Moreover, a GC-MS methodology was also developed for the simultaneous determination of these compounds in a single run; optimal derivatization conditions were achieved using hexamethyldisilazane and N,O-bis(trimethylsilyl)trifluoroacetamide with 1% trimethylchlorosilane. Artichoke receptacle extracts were the richest in caffeoylquinic acids (28-35 mg g -1 dry sample), followed by the bracts (9-18 mg g -1 dry sample), while those from leaves showed the highest concentrations of inositols (up to 15 mg g -1 dry sample). Receptacle extracts also had the highest antioxidant activity (123 mg TE g -1 dry sample) and the greatest concentration of total phenolic compounds (47 mg GAE g -1 dry sample). Therefore, the developed methodology could be considered as a valuable procedure to obtain and characterize bioactive ingredients with industrial interest from artichoke byproducts, opening new routes of revalorization of artichoke agro-industrial residues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier B.V.)

The identification of idiopathic infertility cases, actually, is impossible. Among new functional tests, developed to improve the male fertility diagnosis, the evaluation of spermatic myo-inositol (MI) level, known as Andrositol ® test (AT), is one of the most interesting, considering its weak economic burden and ease of use. The aim of this study was to evaluate the predictive power of AT and its potential use for a preliminary evaluation of semen samples. To evaluate the predictive power of AT, 87 sperm samples were analysed in comparison with spermiogram and sperm chromatin dispersion (SCD) Test, the gold standard analyses for male fertility evaluation. The application of AT resulted very useful for a preliminary sample evaluation, predicting the absence of DNA fragmentation in case of Low Responder samples precisely, and the presence of DNA fragmentation in case of medium or High Responder samples with abnormal morphology, predicting SCD results with a probability of 80% for Medium Responder sample and of 96.7% for High Responder sample. Considering the predictive power of this method, we could imagine, as preliminary qualitative analysis, its application before SCD test, deepening sperm analysis, improving the daily activities of laboratory operators and maintaining a good reliability of sperm evaluation., (© 2019 Blackwell Verlag GmbH.)

Validamycin is the most active component of the antibiotic and antifungal validamycin complex. Since it is widely used to protect rice crops, its persistence in soil and rice matrices may affect the quality and the health of the consumer. Methods for its estimation from soil matrices are not available. Besides, its analysis from complex matrices including grain and paddy husk is challenging. So very few reliable analytical methods are available for its residue analysis. Thus, we aimed to develop a new QuPPe technique and new HPLC-ESI-MS/MS analytical method for the estimation of validamycin in grain, paddy husk, and soil. The QuPPe method was validated with a linearity range of 0.00101 to 0.10134 μg/mL. The LOQ of validamycin in grain, paddy husk, and soil was 1.01013 μg/kg and the retention time was 5.62 min. These results will be helpful in further analysis of food safety and environmental pollution.

A modified sensitive, cheap and simple enzymatic assay method is described for the quantitation of inositol (6-carbon polyol) in human placental tissue. Water-soluble and total (water-soluble and lipid-bound) inositol isomers were extracted and quantified using a 96-well adaptation of the Megazyme® assay. This assay specifically recognized myo-inositol (predominant isomer), d-chiro-, epi-, and allo-inositols, but not scyllo-inositol, glucose or fucose. In term placenta, water-soluble and total inositol contents were high [489 (±58) and 635 (±69) μg/g respectively], and reliably quantified with good reproducibility. This modified assay could facilitate placental inositol biology research, particularly pertinent now with interest in myo-inositol supplementation for gestational diabetes (GDM) prevention., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim was to evaluate the diuretic and neuropharmacological actions of d-pinitol and describe a possible mechanism of action. The diuretic effects of d-pinitol were evaluated using mice placed in metabolic cages. The sedative, anxiolytic-like, antidepressant-like, and anticonvulsant effects of 1-100 mg/kg d-pinitol were assessed. The possible mechanisms of action of the anxiolytic-like, antidepressant-like, and anticonvulsant effects of d-pinitol were evaluated using inhibitors. d-pinitol lacked diuretic effects. However, d-pinitol showed the highest anxiolytic-like actions (ED 50  = 70 mg/kg p.o. in mice) in the cylinder exploratory test and the highest antidepressant-like activity in the forced swimming test (ED 50  = 26 mg/kg p.o. in mice). d-pinitol (100 mg/kg) exerted anticonvulsant actions in the pentylenetetrazole-induced seizures test. The pre-treatment with 2 mg/kg flumazenil reverted the anxiolytic-like actions and the anticonvulsant effects of d-pinitol, whereas the pre-treatment with 1 mg/kg yohimbine and 0.05 mg/kg prazosin abolished the antidepressant effects of d-pinitol. PRACTICAL APPLICATIONS: d-pinitol (3-O-methyl-d-chiro-inositol) is a polyol found in many fruits, as well as in many members of the Leguminosae and Fabaceae families. The results propose that this compound could contribute in the treatment of anxiety, depression, and convulsions. The findings suggest the possible participation of the GABAergic system in the anxiolytic-like and anticonvulsant actions of d-pinitol, whereas the noradrenergic system is probably involved in the antidepressant effects of d-pinitol. This study provides new information about other pharmacological uses for d-pinitol., (© 2019 Wiley Periodicals, Inc.)

Cortical hyperexcitability has been found in early Amyotrophic Lateral Sclerosis (ALS) and is hypothesized to be a key factor in pathogenesis. The current pilot study aimed to investigate cortical inhibitory/excitatory balance in ALS using short-echo Magnetic Resonance Spectroscopy (MRS). Patients suffering from ALS were scanned on a 3 T Trio Siemens MR scanner using Spin Echo Full Intensity Acquired Localized (SPECIAL) Magnetic Resonance Spectroscopy in primary motor cortex and the occipital lobe. Data was compared to a group of healthy subjects. Nine patients completed the scan. MRS data was of an excellent quality allowing for quantification of a range of metabolites of interest in ALS. In motor cortex, patients had Glutamate/GABA and GABA/Cr- ratios comparable to healthy subjects. However, Glutamate/Cr (p = 0.002) and the neuronal marker N-acetyl-aspartate (NAA/Cr) (p = 0.034) were low, possibly due to grey-matter atrophy, whereas Glutathione/Cr (p = 0.04) was elevated. In patients, NAA levels correlated significantly with both hand strength (p = 0.027) and disease severity (p = 0.016). In summary SPECIAL MRS at 3 T allows of reliable quantification of a range of metabolites of interest in ALS, including both excitatory and inhibitory neurotransmitters. The method is a promising new technique as a biomarker for future studies on ALS pathophysiology and monitoring of disease progression.

1 H magnetic resonance spectroscopy (MRS) can reveal changes in brain biochemistry in vivo in humans and has been applied to late onset Alzheimer disease (AD). Carriers of mutations for autosomal dominant Alzheimer disease (ADAD) may show changes in levels of metabolites prior to the onset of clinical symptoms. Proton MR spectra were acquired at 1.5 T for 16 cognitively asymptomatic or mildly symptomatic mutation carriers (CDR < 1) and 11 non-carriers as part of a comprehensive cross-sectional study of preclinical ADAD. Levels of N-acetyl-aspartate+N-acetyl-aspartyl-glutamate (NAA), glutamate/glutamine (Glx), creatine/phosphocreate (Cr), choline (Cho), and myo-inositol (mI) in the left and right anterior cingulate and midline posterior cingulate and precuneus were compared between mutation carriers (MCs) and non-carriers (NCs) using multivariate analysis of variance with age as a covariate. Among MCs, correlations between metabolite levels and time until expected age of dementia diagnosis were calculated. MCs had significantly lower levels of NAA and Glx in the left pregenual anterior cingulate cortex, and lower levels of NAA and higher levels of mI and Cho in the precuneus compared to NCs. Increased levels of mI were seen in these regions in association with increased proximity to expected age of dementia onset. MRS shows effects of ADAD similar to those seen in late onset AD even during the preclinical period including lower levels of NAA and higher levels of mI. These indices of neuronal and glial dysfunction might serve as surrogate outcome measures in prevention studies of putative disease-modifying agents.

Background: Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry., Objectives: Evaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS)., Methods: Adolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myo-inositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels., Results: Recent exposure to high levels of TRAP was associated with significant increases in myo-inositol (β = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (β = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (β = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels., Conclusions: This is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms., (Copyright © 2019. Published by Elsevier Inc.)

D-pinitol (3-O-methyl-D-chiro-inositol) is a well-known bioactive compound with anti-diabetic and anti-oxidant biological functions. A gas chromatography-mass spectrometry (GC-MS) method was developed for its quantitation in carob syrup, flesh and seed samples originated from Cyprus. The analysis was performed after derivatization of carbohydrates and polyols into trimethylsilyl ether derivatives. D-pinitol was determined in 13 carob syrup samples, in concentrations ranging 65.71 ± 4.60 - 77.72 ± 5.44 mg/g (mean: 68.58 ± 4.80 mg/g, n = 13). In two commercial samples, it was determined in relative medium-low concentrations (21.96 ± 1.54 and 44.71 ± 3.13 mg/g), revealing possible adulteration; however, this needs further investigation. Similarly, it was determined in high concentrations in carob flesh samples, in concentrations ranging 53.20 ± 3.72 - 54.58 ± 3.82 mg/g (mean: 53.81 ± 3.76 mg/g, n = 3). On the other hand, seed samples proved very poor in D-pinitol (

Despite the worldwide consumption of bovine milk, dairy products from small ruminants, such as goat's and sheep's milk, are gaining a large interest especially in the Mediterranean area. The aim of this work was to study the metabolite profiles of 30 sheep's and 28 goat's milk using an untargeted metabolomics approach by a gas chromatography coupled with mass spectrometry (GC-MS) analysis. Results showed several differences in the metabolite profiles: arabitol, citric acid, α-ketoglutaric acid, glyceric acid, myo-inositol, and glycine were more abundant in sheep's milk, while goat's milk had higher levels of mannose-6-phosphate, isomaltulose, valine, pyroglutamic acid, leucine, and fucose. Associations between metabolite profile and milk compositional traits were also found. Predictive capabilities of statistical models indicated a good correlation between the metabolite profile and the protein content in sheep's milk, and with the fat content in goat's milk. This work leads to a better understanding of milk metabolites in small ruminants and their role in the evaluation of milk properties., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Reactive astrocytes exhibit hypertrophic morphology and altered metabolism. Deciphering astrocytic status would be of great importance to understand their role and dysregulation in pathologies, but most analytical methods remain highly invasive or destructive. The diffusion of brain metabolites, as non-invasively measured using diffusion-weighted magnetic resonance spectroscopy (DW-MRS) in vivo, depends on the structure of their micro-environment. Here we perform advanced DW-MRS in a mouse model of reactive astrocytes to determine how cellular compartments confining metabolite diffusion are changing. This reveals myo-inositol as a specific intra-astrocytic marker whose diffusion closely reflects astrocytic morphology, enabling non-invasive detection of astrocyte hypertrophy (subsequently confirmed by confocal microscopy ex vivo). Furthermore, we measure massive variations of lactate diffusion properties, suggesting that intracellular lactate is predominantly astrocytic under control conditions, but predominantly neuronal in case of astrocyte reactivity. This indicates massive remodeling of lactate metabolism, as lactate compartmentation is tightly linked to the astrocyte-to-neuron lactate shuttle mechanism., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To evaluate brain temperature effects of early simian immunodeficiency virus (SIV) infection in rhesus macaques using proton magnetic resonance spectroscopy (MRS) thermometry (MRSt) and to determine whether temperature correlates with brain choline or myo-inositol levels., Methods: Brain temperature was retrospectively determined in serial MRS scans that had been acquired at baseline and at 2 and 4 weeks post-SIV infection (wpi) in 16 monkeys by calculating the chemical shift difference between N-acetylaspartate (NAA) and water peaks in sequentially acquired water-suppressed and unsuppressed point-resolved spectroscopy (PRESS) spectra. Frontal and parietal cortex, basal ganglia, and white matter spectra were analyzed., Results: At 2 wpi, brain and rectal temperatures increased relative to baseline and normalized at 4 wpi. Brain temperatures correlated with choline levels in several brain areas, but not with myo-inositol levels., Conclusion: These data indicate that SIV transiently increases brain temperature soon after infection and that temperature is correlated with transient changes in choline levels. Given that choline levels are associated with brain inflammation in SIV-infected monkeys, our findings suggest that the SIV-induced temperature increase reflects brain inflammation. We conclude that MRSt may be informative in human immunodeficiency virus models and may be useful for assessing effects of treatments that reduce inflammation. This study also illustrates that existing MRS data sets containing unsuppressed water spectra can be used to measure tissue temperature, an important physiological parameter., (© 2019 International Society for Magnetic Resonance in Medicine.)

Aims: To determine the metabolic adaptations to compensated heart failure using a reproducible model of myocardial infarction and an unbiased metabolic screen. To address the limitations in sample availability and model variability observed in preclinical and clinical metabolic investigations of heart failure., Main Methods: Metabolomic analysis was performed on serum and myocardial tissue from rabbits after myocardial infarction (MI) was induced by cryo-injury of the left ventricular free wall. Rabbits followed for 12 weeks after MI exhibited left ventricular dilation and depressed systolic function as determined by echocardiography. Serum and tissue from the viable left ventricular free wall, interventricular septum and right ventricle were analyzed using a gas chromatography time of flight mass spectrometry-based untargeted metabolomics assay for primary metabolites., Key Findings: Unique results included: a two- three-fold increase in taurine levels in all three ventricular regions of MI rabbits and similarly, the three regions had increased inosine levels compared to sham controls. Reduced myocardial levels of myo-inositol in the myocardium of MI animals point to altered phospholipid metabolism and membrane receptor function in heart failure. Metabolite profiles also provide evidence for responses to oxidative stress and an impairment in TCA cycle energy production in the failing heart., Significance: Our results revealed metabolic changes during compensated cardiac dysfunction and suggest potential targets for altering the progression of heart failure., (Published by Elsevier Inc.)

Previously, we found an unidentified sphingolipid in cabbage, and determined it as phytoceramide 1-phosphate (PC1P). PC1P is found to be produced from glycosylinositol phosphoceramide (GIPC) by the action of phospholipase D (PLD) activity. Although GIPC is abundant sphingolipid, especially in cruciferous vegetables, amount of daily intake, digestibility and nutritional activity of GIPC are not well understood. Here, we investigated amounts of GIPC and PC1P in vegetables. GIPC was found in all vegetables examined (13 kinds) at levels 3-20 mg/100 g (wet weight). On the other hand, PC1P was present in limited vegetables which show higher GIPC-PLD activity, such as inner cabbage leaves (5.2 mg/100 g). Because PC1P is formed during homogenization by activated GIPC-PLD, level of PC1P in boiled cabbage leaves was very low. Although digestibility of GIPC is unknown at present, a portion of dietary GIPC is considered to be converted to PC1P during mastication by plant-derived GIPC-PLD activity in some vegetables.

Cycloferin is an extract of the chemicals from the Cyclopia species, which grows only in small areas in the southwest and southeast of South Africa and has been consumed traditionally as a nourishing tea to treat numerous health issues and illnesses. Previous studies report that some of the active compounds in Cycloferin, such as pinitol (a modified sugar) and mangiferin (a glucoside), may reduce blood sugar levels and therefore may be used as a treatment for diabetes. Mangiferin, in particular, has been shown to stimulate carbohydrate oxidation and alleviate some effects of insulin resistance and hyperglycemia. Other active components of Cycloferin include flavones, isoflavones, coumestans, luteolin, 4-hydroxycinnamic acid, polyphenols, and xanthones. These active compounds are antioxidants, which can enhance glucose breakdown, lower blood lipids, and reduce the number of highly reactive compounds known as free radicals, which can alter cellular structure and function when present in large amounts. In this study, we explored the ameliorative effects of Cycloferin by treating streptozotocin- (STZ) injected rats with Cycloferin and evaluating its long-term and short-term effect on blood glucose levels and kidney and liver conditions of the diabetic-rendered rats. Our results demonstrated the ability of Cycloferin to both lower the blood glucose levels and reduce evidence of damage in kidney and liver in diabetic rats with and without exogenous insulin treatment for partial control of diabetic state.

Objective: In the treatment of Bipolar disorder (BD), achieving euthymia is highly complex and usually requires a combination of mood stabilizers. The mechanism of action in stabilizing mood has not been fully elucidated, but alterations in N-Acetylaspartate (NAA), Myo-Inositol (mI) and Choline (Cho) have been implicated. Proton magnetic resonance spectroscopy ( 1 H-MRS) is the gold standard technique for measuring brain NAA, Cho and mI in vivo. The objective of this study was to investigate the association of lithium use in BD type I and brain levels of NAA, mI and Cho in the (anterior cingulate cortex) ACC., Methods: 129 BD type I subjects and 79 healthy controls (HC) were submitted to a 3-Tesla brain magnetic resonance imaging scan ( 1 H-MRS) using a PRESS ACC single voxel (8cm 3 ) sequence., Results: BD patients exhibited higher NAA and Cho levels compared to HC. Lithium prescription was associated with lower mI (combination + monotherapy) and higher NAA levels (monotherapy)., Conclusion: The results observed add to the knowledge about the mechanisms of action of mood stabilizers on brain metabolites during euthymia. Additionally, the observed decrease in mI levels associated with lithium monotherapy is an in vivo finding that supports the inositol-depletion hypothesis of lithium pharmacodynamics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to investigate potential effects of acute caffeine intake on J-difference-edited MRS measures of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA)., Methods: J-difference-edited Mescher-Garwood PRESS (MEGA-PRESS) and conventional PRESS data were acquired at 3T from voxels in the anterior cingulate and occipital area of the brain in 15 healthy subjects, before and after oral intake of a 200-mg caffeine dose. MEGA-PRESS data were analyzed with the MATLAB-based Gannet tool to estimate GABA+ macromolecule (GABA+) levels, while PRESS data were analyzed with LCModel to estimate levels of glutamate, glutamate+glutamine, N-acetylaspartate, and myo-inositol. All metabolites were quantified with respect to the internal reference compounds creatine and tissue water, and compared between the pre- and post-caffeine intake condition., Results: For both MRS voxels, mean GABA+ estimates did not differ before and after caffeine intake. Slightly lower estimates of myo-inositol were observed after caffeine intake in both voxels. N-acetylaspartate, glutamate, and glutamate+glutamine did not show significant differences between conditions., Conclusion: Mean GABA+ estimates from J-difference-edited MRS in two different brain regions are not altered by acute oral administration of caffeine. These findings may increase subject recruitment efficiency for MRS studies., (© 2018 International Society for Magnetic Resonance in Medicine.)

Due to the great interest in obtaining natural bioactive carbohydrates to be used as functional ingredients, a selective microwave assisted extraction (MAE) method was optimized to ensure the exhaustive extraction of inositols and α-galactooligosaccharides (α-GOS) from mung bean. Thereafter, a comprehensive characterization of these compounds was carried out by gas chromatography coupled to mass spectrometry (GC-MS). Apart from free inositols and α-GOS, several glycosyl-methyl-scyllo-inositols and glycosyl-inositols were detected for the first time in this legume. Under optimized MAE conditions (0.5 g dry sample, 2 cycles of 3 min, 50 °C, 10 mL 50:50 ethanol:water, v:v), bioactive carbohydrates yields were similar to those found using solid-liquid extraction (SLE), but with shorter analytical times. Concentrations of bioactive carbohydrates in MAE extracts from samples of different geographical origins ranged between 74.1 and 104.2 mg.g -1 dry sample. MAE was proved a good alternative to SLE to obtain extracts enriched in bioactive carbohydrates., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease., Methods: N-Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot., Results: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice., Conclusion: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.

Context: We previously demonstrated that insulin infusion altered metabolite concentrations in cerebral tissues assessed with proton magnetic resonance spectroscopy (1H-MRS) in young subjects with high insulin sensitivity, but not in those with low insulin sensitivity. Fat overload is an important factor leading to insulin resistance., Objective: The purpose of the current study was to examine the effect of elevated circulating free fatty acid (FFA) levels on metabolites in cerebral tissues assessed with 1H-MRS., Design: The study group comprised 10 young, healthy male subjects. 1H-MRS was performed at baseline and after 4-hour Intralipid (Fresenius Kabi)/heparin or saline infusions administered in random order. Voxels were positioned in the left frontal lobe, left temporal lobe, and hippocampus. The ratios of N-acetylaspartate (NAA), choline (Cho)-containing compounds, myo-inositol (mI), and glutamate/glutamine/γ-aminobutyric acid complex (Glx) to creatine (Cr) and nonsuppressed water signal were determined., Results: Intralipid/heparin infusion resulted in a significant increase in circulating FFAs (P < 0.0001). Significant changes in brain neurometabolite concentrations in response to Intralipid/heparin infusion were increases in frontal mI/Cr (P = 0.041) and mI/H2O (P = 0.037), decreases in frontal and hippocampal Glx/Cr (P = 0.018 and P = 0.015, respectively) and Glx/H2O (P = 0.03 and P = 0.067, respectively), and a decrease in hippocampal NAA/Cr (P = 0.007) and NAA/H2O (P = 0.019). No changes in neurometabolites were observed during the saline infusion., Conclusions: Acute circulating FFA elevation influenced cerebral metabolites in healthy humans and lipid-induced insulin resistance could be partly responsible for these effects.

Quercitol is a cyclohexanepentol that has been recognized as a biomarker of plants in genus Quercus, which includes oak. As a result of its glucose-like structure, it has been introduced as an alternative chiral building block in the synthesis of several bioactive compounds. Our continuing investigations on the synthesis of antidiabetic agents from quercitol have demonstrated that this chiral synthon can generate diverse structural features with improved hypoglycemic activity.

Ilex paraguariensis (mate) is a species native to South America and is widely consumed in countries such Argentina, Uruguay, Paraguay, and Brazil. Mate consumption is associated with several phytotherapeutic functions, in addition to its cultural and regional importance. However, the harvest period can affect the properties of the mate, due to variations in the constituent proportions, as a consequence of seasonal changes. In this work, we employed nuclear magnetic resonance and chemometrics to evaluate the chemical variations in leaf extracts of I. paraguariensis over the four seasons of the year. We found significant changes in the levels of glucose, myo-inositol, caffeine, theobromine, and fatty acids. These changes can be related to resource allocation for the flowering period, or to responses to environmental stresses, such as temperature., (Copyright © 2018 John Wiley & Sons, Ltd.)

The toxic effect of ethanol is one of the most important handicaps for many biotechnological applications of yeasts, such as bioethanol production. Elucidation of ethanol stress response will help to improve yeast performance in biotechnological processes. In the yeast Saccharomyces cerevisiae, ethanol stress has been recently described as an activator of the unfolded protein response (UPR), a conserved intracellular signalling pathway that regulates the transcription of ER homoeostasis-related genes. However, the signal and activation mechanism has not yet been unravelled. Here, we studied UPR's activation after ethanol stress and observed the upregulation of the key target genes, like INO1, involved in lipid metabolism. We found that inositol content influenced UPR activation after ethanol stress and we observed significant changes in lipid composition, which correlate with a major membrane fluidity alteration by this amphipathic molecule. Then, we explored the hypothesis that membrane fluidity changes cause UPR activation upon ethanol stress by studying UPR response against fluidification or rigidification agents and by studying a mutant, erg2, with altered membrane fluidity. The results suggest that the membrane fluidification effects of ethanol and other agents are the signal for UPR activation, a mechanism that has been proposed in higher eukaryotes., (© 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

Two polar aminoglycosides, kasugamycin and validamycin-A, were determined in cereals (brown rice, wheat and corn) by high-performance liquid chromatography-tandem mass spectrometry. The analytes were extracted from samples using methanol and water (70:30, v/v) at pH 5.5, purified using both a hydrophilic-hydrophobic-balanced cartridge and a strong cation-exchange cartridge, and then analysed using multiple reaction monitoring in positive electrospray ionisation mode with a special ReproSil 100 C 18 high-performance liquid chromatography column. This newly proposed method yielded good sensitivity and excellent chromatographic performance. The limits of quantification for kasugamycin and validamycin-A were 4.1 µg/kg and 1.0 µg/kg, respectively. The recoveries for both compounds at three fortification levels (4, 100 and 500 µg/kg for kasugamycin; 1, 10 and 100 µg/kg for validamycin-A) ranged from 75% to 110%, and the relative standard deviations were below 15%.

The targeted analysis of metabolites in complex mixtures is a challenging issue. NMR is one of the major tools in this field, but there is a strong need for more sensitive, better-resolved, and faster quantitative methods. In this framework, we introduce the concept of FAst, QUantitative, hIghly Resolved and sEnsitivity enhanced (FAQUIRE) NMR to push forward the limits of metabolite NMR analysis. 2D 1 H, 13 C 2D quantitative maps are promising alternatives for enhancing the spectral resolution but are highly time-consuming because of (i) the intrinsic nature of 2D, (ii) the longer recycling times required for quantitative conditions, and (iii) the higher number of scans needed to reduce the level of detection/quantification to access low concentrated metabolites. To reach this aim, speeding up the recently developed QUantItative Perfected and pUre shifted HSQC (QUIPU HSQC) is an interesting attempt to develop the FAQUIRE concept. Thanks to the combination of spectral aliasing, nonuniform sampling, and variable repetition time, the acquisition time of 2D quantitative maps is reduced by a factor 6 to 9, while conserving a high spectral resolution thanks to a pure shift approach. The analytical potential of the new Quick QUIPU HSQC (Q QUIPU HSQC) is evaluated on a model metabolite sample, and its potential is shown on breast-cell extracts embedding metabolites at millimolar to submillimolar concentrations.

Type 2 diabetes drug tablets containing voglibose having dose strengths of 0.2 and 0.3 mg of various brands have been examined, using laser-induced breakdown spectroscopy (LIBS) technique. The statistical methods such as the principal component analysis (PCA) and the partial least square regression analysis (PLSR) have been employed on LIBS spectral data for classifying and developing the calibration models of drug samples. We have developed the ratio-based calibration model applying PLSR in which relative spectral intensity ratios H/C, H/N and O/N are used. Further, the developed model has been employed to predict the relative concentration of element in unknown drug samples. The experiment has been performed in air and argon atmosphere, respectively, and the obtained results have been compared. The present model provides rapid spectroscopic method for drug analysis with high statistical significance for online control and measurement process in a wide variety of pharmaceutical industrial applications.

It is sometimes difficult to distinguish gliomas from other tumors on routine imaging. In this study, we assessed whether 3-T magnetic resonance spectroscopy (MRS) with LCModel software might be useful for discriminating glioma from other brain tumors, such as primary central nervous system lymphomas (PCNSLs) and metastatic tumors. A total of 104 cases of brain tumor (66 gliomas, 20 PCNSLs, 6 metastatic tumors, 12 other tumors) were preoperatively investigated with short echo time (35 ms) single-voxel 3-T MRS. LCModel software was used to evaluate differences in the absolute concentrations of choline, N-acetylaspartate, N-acetylaspartylglutamate, glutamate + glutamine, myo-inositol (mIns), and lipid. mIns levels were significantly increased in high-grade glioma (HGG) compared with PCNSL (p < 0.001). In multivariate logistic regression analysis, mIns was the best marker for differentiating HGG from PCNSL (p < 0.0001, odds ratio 1.9927, 95% confidence interval 1.3628-3.2637). Conventional MRS detection of mIns resulted in a high diagnostic accuracy (sensitivity, 64%; specificity, 90%; area under the receiver operator curve, 0.80) for HGG. The expression of inositol 3-phosphate synthase (ISYNA1) was significantly higher in gliomas than in PCNSLs (p < 0.05), suggesting that the increased level of mIns in glioma is due to high expression of ISYNA1, the rate-limiting enzyme in the mIns-producing pathway. In conclusion, noninvasive analysis of mIns using single-voxel MRS may be useful in distinguishing gliomas from other brain tumors, particularly PCNSLs.

Objective: It was previously shown that higher concentrations of myo-inositol in human follicular fluid improve oocyte and embryo quality, whereas D-chiro-inositol seems to worsen oocyte quality and ovarian response in polycystic ovary syndrome patients. Our study was the first one aiming to test whether different myo-inositol and D-chiro-inositol concentration in follicular fluids correlate with blastocyst quality in healthy young women., Patients and Methods: Eight egg donors and eleven couples undergoing in vitro fertilization, were involved in a prospective observational study. Myo-inositol/D-chiro-inositol ratio was calculated in the follicular fluids and associated with different blastocyst grades. Donors were homogeneous and followed the same standard stimulation protocol., Results: The ratio between myo-inositol and D-chiro-inositol was significantly higher in the specimens rated as good quality blastocysts, compared to those rated as poor-quality blastocysts. In this study, almost all the transferred blastocysts were graded as good quality and were correlated to lower D-chiro-inositol content in the follicular fluid; the implantation rate and pregnancy rate were satisfying. Our data suggest that the reduction of such ratio in follicular fluid seems to play a negative role in follicular development., Conclusions: We found a correlation between myo-inositol/D-chiro-inositol ratio in follicular fluid and blastocyst quality. The value of this ratio may represent a new biomarker for estimating the good features of blastocysts, and a prognostic factor of embryo implantation and pregnancy success. Moreover, the pre-treatment with myo-inositol in women undergoing in vitro fertilization (IVF) may improve oocyte quality and ART outcome., Clinical Trial Registration Number: NCT03055442 (ClinicalTrials.gov registry).

During exposure of yeast cells to low levels of hydrogen peroxide (H 2 O 2 ), the expression of several genes is regulated for cells to adapt to the surrounding oxidative environment. Such adaptation involves modification of plasma membrane lipid composition, reorganization of ergosterol-rich microdomains and altered gene expression of proteins involved in lipid and vesicle traffic, to decrease permeability to exogenous H 2 O 2 . Opi1p is a transcriptional repressor that is inactive when present at the nuclear membrane/endoplasmic reticulum, but represseses transcription of inositol upstream activating sequence (UAS INO )-containing genes, many of which are involved in the synthesis of phospholipids and fatty acids, when it is translocated to the nucleus. We investigated whether H 2 O 2 in concentrations inducing adaptation regulates Opi1p function. We found that, in the presence of H 2 O 2 , GFP-Opi1p fusion protein translocates to the nucleus and, concomitantly, the expression of UAS INO -containing genes is affected. We also investigated whether cysteine residues of Opi1p were implicated in the H 2 O 2 -mediated translocation of this protein to the nucleus and identified cysteine residue 159 as essential for this process. Our work shows that Opi1p is redox-regulated and establishes a new mechanism of gene regulation involving Opi1p, which is important for adaptation to H 2 O 2 in yeast cells. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

The aim of this study was to examine brain neurometabolite concentrations in retired rugby league players who had a history of numerous self-reported concussions. Participants were 16 retired professional rugby league players (ages 30-45 years) with an extensive history of concussion and participation in contact sports, and 16 age- and education-matched controls who had no history of neurotrauma or participation in contact sports. All completed a clinical interview, psychological and cognitive testing, and magnetic resonance spectroscopy (MRS) investigation. MRS voxels were placed in posterior cingulate grey matter and parietal white matter. Neurometabolite concentrations were quantified using LCModel. It was hypothesized that retired athletes would differ on N-acetyl aspartate, myo-inositol, choline, glutamate, and glutathione. Retired players had significantly lower concentrations of grey matter glutathione (p=0.02, d=0.91). They did not significantly differ in concentrations of other neurometabolites. There were no significant differences between groups on measures of depression, anxiety, or cognitive functioning. The retired athletes reported significantly greater alcohol use (p<0.01; Cohen's d=1.49), and they had worse manual dexterity using their non-dominant hand (p=0.03; d=1.08). These preliminary findings suggest that MRS might be modestly sensitive to biochemical differences in athletes after their athletic careers have ended in the absence of clinical differences in cognitive performance and self-reported psychological functioning., (© Georg Thieme Verlag KG Stuttgart · New York.)

Validamycin A (Val-A), produced by Streptomyces hygroscopicus 5008 in industrial fermentation, is one of the most widely used anti-fungal agro-antibiotics in Asia and high performance liquid chromatography (HPLC) assay is usually used to determine the production of Val-A. A new approach to determine Val-A by spectrophotometer is developed. During the fermentation of S. hygroscopicus 5008, a pigment secretion was found along with the Val-A biosynthesis. There was a stable relationship between the concentration of Val-A and spectral absorption (SA) value of this pigment at 450 nm, even in different fermentation cultures or conditions. Using SA value as interior label, a rapid spectrophotometric method for determining Val-A production was established. In comparing Val-A productivity by HPLC method with that by SA method, the relative standard deviation (R.S.D.) was 0.007 (less than 0.05, no variation) and the conditional probability [Pr(T < t)] was 0.3491 (greater than 0.05, no difference) at the optimal time point of Val-A fermentation, which demonstrated SA method was as stable and accurate as standard HPLC method. It was applied successfully to finding positive strains with high Val-A productivity and short fermentation time. SA assay is an accurate and cost-effective method for measuring Val-A and screening high-producing strains, and this work provides a new insight for rapid quantitative analysis of antibiotics in fermentation of pigment-producing strains., (Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

The available components in the flesh of litchi seem insufficient to interpret its wide and significant physiological effects. Some unusual compounds, including myo-inositol, inositol methyl derivatives and γ-aminobutyric acid (GABA) were identified as main constituents in the flesh of litchi. Their concentrations varied among cultivars but remain relatively constant during development. Litchi flesh was shown to contain moderate myo-inositol (0.28-0.78 mg g(-1) FW), ascorbic acid (0.08-0.39 mg g(-1) FW) and phenolics (0.47-1.60 mg g(-1) FW), but abundant l-quebrachitol (1.6-6.4 mg g(-1) FW) and GABA (1.7-3.5 mg g(-1) FW). The concentration of GABA in the flesh of litchi was about 100 times higher than in other fruits. And l-quebrachitol is not a common component in fruits. The biological and physiological activities of inositols, inositol derivatives and GABA have been extensively documented. These compounds are probably important compositional characteristic contributing to the widely shown health benefits of litchi.

The critical role of metabolic abnormality in hypertension is increasingly recognized, but its biomarkers are not clearly identified. In this study, 47 chemical compounds recorded by literature were employed as target metabolites of essential hypertension (EH). We detected their content in the plasma of EH patients and healthy subjects by using the Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS). After screening the most altered compounds, acupuncture was used to treat patients for 3 months and these plasma metabolites were tested again. The results showed that oleic acid (OA) and myoinositol (MI) were the most important differential metabolites between the hypertensive plasma and the healthy plasma. They were also closely correlated with 24-hour blood pressure and nocturnal dipping. Moreover, plasma OA and MI could be restored to normal levels by acupuncture, accompanying with reduction of 24-hour systolic and diastolic blood pressure [from 145.10 ± 9.28 mm Hg to 140.70 ± 9.59 mm Hg (P < 0.0001), and 88.35 ± 7.92 mm Hg to 85.86 ± 7.95 mm Hg (P = 0.0024), respectively] and improvement of circadian blood pressure rhythm. This study demonstrated that plasma OA and MI were potential hypertension biomarkers and they could be used to preliminarily assess the treating effects such as acupuncture.

Objective: The objective of this study is to assess the correlation between the degree of degeneration of lumbar discs according to the Pfirrmann classification system and the concentrations of metabolites determined by means of 1H high-resolution magic angle spinning nuclear magnetic resonance (1H HR MAS NMR) spectroscopy., Materials and Methods: Twenty-six human intervertebral lumbar discs that were operated on due to degenerative disease were analyzed. Routine preoperative 1.5T, T2-weighed magnetic resonance (MR) images were used to classify the cases according to the Pfirrmann classification system. In all the cases, during microdiscectomy, the fragments of the annulus fibrosus and nucleus pulposus were harvested and their metabolic profile was examined by means of 1H HR MAS. The grades of disc degeneration on the Pfirrmann scale were correlated with the metabolite concentrations., Results: Spectral analyses of the intervertebral discs with Pfirrmann grades IV and V demonstrated significantly higher concentrations of creatine, glycine, hydroxyproline, alanine, leucine, valine, acetate, isoleucine, α,β-glucose, and myo-inositol, and a lower intensity of the N-acetyl peak of chondroitin sulfate, compared to the spectra with Pfirrmann grade III., Conclusion: Our results demonstrate correlations between metabolite concentrations and the degree of lumbar disc degeneration assessed using the Pfirrmann grading system and provide another step toward the potential use of in vivo MR spectroscopy for investigation of biomarkers in lumbar disc degeneration., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Powder-like extract of Ricinus communis seeds contain a toxic protein, ricin, which has a history of military, criminal and terroristic use. As the detection of ricin in this "terrorist powder" is difficult and time-consuming, related low mass metabolites have been suggested to be useful for screening as biomarkers of ricin., Objective: To apply a comprehensive NMR-based analysis strategy for annotation, isolation and structure elucidation of low molecular weight plant metabolites of Ricinus communis seeds., Methodology: The seed extract was prepared with a well-known acetone extraction approach. The common metabolites were annotated from seed extract dissolved in acidic solution using (1)H NMR spectroscopy with spectrum library comparison and standard addition, whereas unconfirmed metabolites were identified using multi-step off-line HPLC-DAD-NMR approach., Results: In addition to the common plant metabolites, two previously unreported compounds, 1,3-digalactoinositol and ricinyl-alanine, were identified with support of MS analyses., Conclusion: The applied comprehensive NMR-based analysis strategy provided identification of the prominent low molecular weight metabolites with high confidence., (Copyright © 2015 John Wiley & Sons, Ltd.)

This study reports a method for the analysis of mannitol, sorbitol and myo-inositol in olive tree roots and rhizospheric soil with gas chromatography. The analytical method consists of extraction with a mixture of dichloromethane:methanol (2:1, v/v) for soil samples and a mixture of ethanol:water (80:20) for root samples, silylation using pyridine, hexamethyldisilazane (HMDS) and trimethylchlorosilane (TMCS). The recovery of mannitol sorbitol and myo-inositol (for extraction and analysis in dichloromethane:methanol and ethanol:water) was acceptable and ranged from 100.3 to 114.7%. The time of analysis was <24 min. Among identified polyols extracted from rhizosphere and roots of olive plants, mannitol was the major compound. A marked increase in mannitol content occurred in rhizosphere and roots of water-stressed plants, suggesting a much broader role of mannitol in stress response based on its ability to act as a compatible solute., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)