Myo-inositol Concentrations Research Articles

Astrocytic function is associated with both amyloid-β and tau pathology in non-demented APOE ϵ4 carriers.

A growing body of evidence suggests that astrocytes play a major role in the pathophysiology of Alzheimer’s disease. Given that APOE is primarily expressed in astrocytes, these cells might be an important link between the APOE ε4 allele and the development of Alzheimer’s disease pathology. Here, we investigate this hypothesis in vivo by measuring myo-inositol, a metabolite involved in astrocytic functions, with magnetic resonance spectroscopy. Currently, there is conflicting evidence regarding the relationship between APOE ε4 and myo-inositol concentration. Furthermore, data supporting a relationship between APOE ε4, myo-inositol and Alzheimer’s disease pathology (amyloid-beta and tau proteins) in the preclinical stage of Alzheimer’s disease are limited. A previous study revealed differences in myo-inositol levels between APOE ε4 carriers and non-carriers already in preclinical Alzheimer’s disease participants. However, other reports showed no impact of APOE genotype on the association between myo-inositol and the rate of amyloid-beta accumulation. In the present study, we determined the effect of APOE genotype on the association between myo-inositol and both amyloid-β and tau deposition quantified by PET in 428 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER-2 cohort. APOE genotype impacted the associations between myo-inositol and amyloid-β pathology as revealed by an interaction effect between APOE genotype and levels of myo-inositol (P < 0.001) such that higher myo-inositol concentration was related to more amyloid-beta pathology in APOE ε4 carriers only. A similar interaction effect was also found when investigating the effect of APOE on the association between myo-inositol and tau pathology (P < 0.01). Focusing on the APOE ε4 subsample, myo-inositol partially (17%) mediated the association between amyloid-beta and tau pathology (P < 0.05). Furthermore, in a subgroup of participants with available plasma levels of glial fibrillary acidic protein, a marker of astroglial activation and astrocytosis, we found that glial fibrillary acidic protein correlated with myo-inositol only in APOE e4 carriers (APOE ε4 carriers: P < 0.01; APOE ε4 non-carriers: P > 0.8), suggesting that myo-inositol might reflect an aspect of the astrocytic involvement in Alzheimer’s pathology which is specific to the impact of APOE ε4. Therefore, we suggest that myo-inositol is a candidate in vivo marker to study the impact of APOE ε4 on the interplay between astrocytes and the pathophysiology of Alzheimer’s disease.

New insights into the influence of myo-inositol on carbohydrate metabolism during osmoregulation in Nile tilapia (Oreochromis niloticus).

A two-factor (2 × 3) orthogonal test was conducted to investigate the effects of dietary myo-inositol (MI) on the osmoregulation and carbohydrate metabolism of euryhaline fish tilapia (Oreochromis niloticus) under sustained hypertonic stress (20 practical salinity units [psu]). 6 diets containing either normal carbohydrate (NC, 30%) or high carbohydrate (HC, 45%) levels, with 3 levels (0, 400 and 1,200 mg/kg diet) of MI, respectively, were fed to 540 fish under 20 psu for 8 weeks. Dietary MI supplementation significantly improved growth performance and crude protein content of whole fish, and decreased the content of crude lipid of whole fish (P < 0.05). Curled, disordered gill lamella and cracked gill filament cartilage were observed in the gill of fish fed diets without MI supplementation. The ion transport capacity in gill was significantly improved in the 1,200 mg/kg MI supplementation groups compared with the 0 mg/kg MI groups (P < 0.05). Moreover, the contents of Na+, K+, Cl− in serum were markedly reduced with the dietary MI supplementation (P < 0.05). The fish fed 1,200 mg/kg MI supplementation had the highest MI content in the gills and the lowest MI content in the serum (P < 0.05). Additionally, the fish fed with 1,200 mg/kg MI supplementation had the highest MI synthesis capacity in gills and brain (P < 0.05). Dietary MI markedly promoted the ability of carbohydrate metabolism in liver (P < 0.05). Moreover, fish in the 1,200 mg/kg MI groups had the highest antioxidant capacity (P < 0.05). This study indicated that high dietary carbohydrate would intensify stress, and impair the ability of osmoregulation in tilapia under a long-term hypersaline exposure. The supplementation of MI at 1,200 mg/kg in the high carbohydrate diet could promote carbohydrate utilization and improve the osmoregulation capacity of tilapia under long-term hypertonic stress.

Quantification of Myoinositol in Serum by Electrochemical Detection with an Unmodified Screen-Printed Carbon Electrode.

Simple, rapid, and accurate detection of myoinositol (MI) concentration in blood is crucial in diagnosing polycystic ovary syndrome, neurological disorders, and cancer. A novel electrochemical detection (IED) method was established to quantify MI in human serum using a disposable unmodified screen-printed carbon electrode (SPCE) for the first time. MI was detected indirectly by the reaction product of myoinositol dehydrogenase (IDH) and cofactor β-nicotinamide adenine dinucleotide (NAD+). Good linear calibration curves were obtained at the concentration range from 5.0 μM to 500.0 μM (R2 = 0.9981) with the lower limits of detection (LOD) and quantification (LOQ) of 1.0 μM and 2.5 μM, respectively. Recoveries were calculated at three spiked concentrations, and the values were between 90.3 and 106%, with relative standard deviation values of 3.2–6.2% for intraday precision and 7.1–9.0% for interday precision. The SPCE-electrochemical biosensor is simple, accurate, and without modification, showing great potential for point-of-care testing (POCT) of serum MI in clinical samples.

A Neurometabolic Pattern of Elevated Myo-Inositol in Children Who Are HIV-Exposed and Uninfected: A South African Birth Cohort Study.

IntroductionExposure to maternal HIV in pregnancy may be a risk factor for impaired child neurodevelopment during the first years of life. Altered neurometabolites have been associated with HIV exposure in older children and may help explain the mechanisms underlying this risk. For the first time, we explored neurometabolic profiles of children who are HIV-exposed and uninfected (CHEU) compared to children who are HIV-unexposed (CHU) at 2-3 years of age.MethodsThe South African Drakenstein Child Health Study enrolled women during pregnancy and is following mother-child pairs through childhood. MRI scans were acquired on a sub-group of children at 2-3 years. We used single voxel magnetic resonance spectroscopy to measure brain metabolite ratios to total creatine in the parietal grey matter, and left and right parietal white matter of 83 children (36 CHEU; 47 CHU). Using factor analysis, we explored brain metabolite patterns in predefined parietal voxels in these groups using logistic regression models. Differences in relative concentrations of individual metabolites (n-acetyl-aspartate, myo-inositol, total choline, and glutamate) to total creatine between CHEU and CHU groups were also examined.ResultsFactor analysis revealed four different metabolite patterns, each one characterized by covarying ratios of a single metabolite in parietal grey and white matter. The cross-regional pattern dominated by myo-inositol, a marker for glial reactivity and inflammation, was associated with HIV exposure status (OR 1.63; 95% CI 1.11–2.50) which held after adjusting for child age, sex, and maternal alcohol use during pregnancy (OR 1.59; 95% CI 1.07 –2.47). Additionally, higher relative concentrations of myo-inositol to total creatine were found in left and right parietal white matter of CHEU compared to CHU (p=0.025 and p=0.001 respectively).DiscussionIncreased ratios of myo-inositol to total creatine in parietal brain regions at age 2-3 years in CHEU are suggestive of early and ongoing neuroinflammatory processes. Altered relative concentrations of neurometabolites were found predominantly in the white matter, which is sensitive to neuroinflammation, and may contribute to developmental risk in this population. Future work on the trajectory of myo-inositol over time in CHEU, alongside markers of neurocognitive development, and the potential for specific neurodevelopmental interventions will be useful.

Effect of phytase supplementation on plasma and organ myo-inositol content and erythrocyte inositol phosphates as pertaining to breast meat quality issues in chickens

‘Woody breast’ (WB) and ‘white striping’ in broiler meat is a global problem. With unknown etiology, WB negatively impacts bird health, welfare and is a significant economic burden to the poultry industry. New evidence has shown that WB is associated with dysregulation in systemic and breast muscle-oxygen homeostasis, resulting in hypoxia and anaemia. However, it has been observed that phytase (Quantum Blue (QB) a modified, E. coli-derived 6-phytase) super dosing can reverse dysregulation of muscle-oxygen homeostasis and reduces WB severity by ~5%. The objective of this study was to assess whether levels of Ins(1,3,4,5,6)P 5, the main allosteric regulator of haemoglobin, are influenced by changes in plasma myo-inositol arising from super dosing with phytase. To enable this, methods suitable for measurement of myo-inositol in tissues and inositol phosphates in blood were developed. Data were collected from independent trials, including male Ross 308 broilers fed low and adequate calcium/available phosphate (Ca/AvP) diets supplemented with QB at 1,500 phytase units (FTU)/kg, which simultaneously decreased gizzard InsP 6 (P&lt;0.001) and increased gizzard myo-inositol (P&lt;0.001). Similarly, male Cobb 500 broiler chicks fed a negative control (NC) diet deficient in AvP, Ca and sodium or diet supplemented with the QB phytase at 500, 1000 or 2,000 FTU/kg increased plasma (P&lt;0.001) and liver (P=0.007) myo-inositol of 18d-old birds at 2,000 FTU/kg. Finally, QB supplementation of Cobb 500 breeder flock diet at 1,250 FTU/kg increased blood myo-inositol (P&lt;0.001) and erythrocyte Ins(1,3,4,5,6)P 5 (P=0.011) of their 1d-old hatchlings. These data confirmed the ability of phytase to modulate inositol phosphate pathways by provision of metabolic precursors of important signalling molecules. The ameliorations of WB afforded by super doses of phytase may include modulation of hypoxia pathways that also involve inositol signalling molecules. Elevations of erythrocyte Ins(1,3,4,5,6)P 5 by phytase supplementation may enhance systemic oxygen carrying capacity, an important factor in the amelioration of WB and WS myopathy.

Characterizing cerebral metabolite profiles in anorexia and bulimia nervosa and their associations with habitual behavior

Anorexia nervosa (AN) and bulimia nervosa (BN) are associated with altered brain structure and function, as well as increased habitual behavior. This neurobehavioral profile may implicate neurochemical changes in the pathogenesis of these illnesses. Altered glutamate, myo-inositol and N-acetyl aspartate (NAA) concentrations are reported in restrictive AN, yet whether these extend to binge-eating disorders, or relate to habitual traits in affected individuals, remains unknown. We therefore used single-voxel proton magnetic resonance spectroscopy to measure glutamate, myo-inositol, and NAA in the right inferior lateral prefrontal cortex and the right occipital cortex of 85 women [n = 22 AN (binge-eating/purging subtype; AN-BP), n = 33 BN, n = 30 controls]. To index habitual behavior, participants performed an instrumental learning task and completed the Creature of Habit Scale. Women with AN-BP, but not BN, had reduced myo-inositol and NAA concentrations relative to controls in both regions. Although patient groups had intact instrumental learning task performance, both groups reported increased routine behaviors compared to controls, and automaticity was related to reduced prefrontal glutamate and NAA participants with AN-BP. Our findings extend previous reports of reduced myo-inositol and NAA levels in restrictive AN to AN-BP, which may reflect disrupted axonal-glial signaling. Although we found inconsistent support for increased habitual behavior in AN-BP and BN, we identified preliminary associations between prefrontal metabolites and automaticity in AN-BP. These results provide further evidence of unique neurobiological profiles across binge-eating disorders.

Control of fruit softening and Ascorbic acid accumulation by manipulation of SlIMP3 in tomato.

SummaryPostharvest deterioration is among the major challenges for the fruit industry. Regulation of the fruit softening rate is an effective strategy for extending shelf‐life and reducing the economic losses due postharvest deterioration. The tomato myoinositol monophosphatase 3 gene SlIMP3, which showed highest expression level in fruit, was expressed and purified. SlIMP3 demonstrated high affinity with the L‐Gal 1‐P and D‐Ins 3‐P, and acted as a bifunctional enzyme in the biosynthesis of AsA and myoinositol. Overexpression of SlIMP3 not only improved AsA and myoinositol content, but also increased cell wall thickness, improved fruit firmness, delayed fruit softening, decreased water loss, and extended shelf‐life. Overexpression of SlIMP3 also increased uronic acid, rhamnose, xylose, mannose, and galactose content in cell wall of fruit. Treating fruit with myoinositol obtained similar fruit phenotypes of SlIMP3‐overexpressed fruit, with increased cell wall thickness and delayed fruit softening. Meanwhile, overexpression of SlIMP3 conferred tomato fruit tolerance to Botrytis cinerea. The function of SlIMP3 in cell wall biogenesis and fruit softening were also verified using another tomato species, Ailsa Craig (AC). Overexpression of SlDHAR in fruit increased AsA content, but did not affect the cell wall thickness or fruit firmness and softening. The results support a critical role for SlIMP3 in AsA biosynthesis and cell wall biogenesis, and provide a new method of delaying tomato fruit softening, and insight into the link between AsA and cell wall metabolism.

Selected Metabolites Found in Equine Oviductal Fluid do not Modify the Parameters Associated to Capacitation of the Frozen-thawed Equine Spermatozoa In Vitro

In the horse, a repeatable protocol for in vitro fertilization has not been developed, possibly due to incomplete sperm capacitation. We have previously identified the metabolites present in equine oviductal fluid (OF). We aimed to test the effects of different metabolites found in equine oviductal fluid on quality parameters of frozen-thawed spermatozoa. Different concentrations of myoinositol (5–25 mM), lactate (6–60 mM), glycine (0.1–5 mM), β-alanine (1–6 mM), and histamine (0.05–0.4 mM) were added independently to modified Whitten's medium (pH = 7.25). Thawed equine spermatozoa (three stallions, one ejaculate per stallion, n = 3) were incubated for 2 hours at 37˚C in presence of the selected metabolites. After sperm incubation, total motility (TM), and progressive motility (PM) were evaluated by computer-assisted sperm analysis. Viability (SYBR-14+/PI−), mitochondrial membrane potential (ΔΨm) (JC-1), acrosome reaction (PNA+/PI−) and reactive oxygen species (ROS) production (CellRox+/PI−), were evaluated by flow cytometry. Protein tyrosine phosphorylation (PY) was evaluated by indirect immunofluorescence. Our results show that the addition of the metabolites at the dosages tested does not exert any effect on the sperm parameters analyzed. More research is needed to ascertain if metabolite addition at the dosages found in the equine OF exerts any remarkable effect on in vitro equine sperm capacitation.

The effect of different temperatures applied during extrusion on the nutritional value of faba bean and degradation of phytic P isomers

This study determined the effect of varying extrusion processing temperatures on the content of phytic P isomers (InsP6–InsP3), myo-inositol, nutrients, and antinutritional factors in faba beans and went on to estimate the nutritional value of these extrudates and the effect they had on InP6-Insp3 contents in the gastrointestinal tract of birds. The study was performed on 240 male Ross 308 strain broiler chicks (1-day old) which were divided into six experimental groups (20 replications/group; two birds/replication). A maize/soybean meal basal diet was mixed (60:40 ratio) with faba beans that were fed either raw or extruded at 110, 115, 120, or 125 °C. The extrusion process decreased the level of trypsin inhibitors, phytic P and resistant starch and reduced the content of InsP6 and increased InsP5, InsP4, and InsP3 and myo-inositol. Digestibility of dry matter, crude protein, starch and apparent metabolisable energy (AME) and nitrogen-corrected (AMEN) of the beans were optimized when they were extruded between 110 and 115 °C. Increasing the temperature of extrusion had a linear and quadratic negative effect on nutrient (except starch) digestibility and AMEN value. Increasing extrusion temperatures also resulted in the reduction in ileal InsP4 and InsP3 and an increase in myo-inositol concentrations. Thus, it can be concluded that extrusion can enhance the nutritional value of faba bean by improving the digestibility of several nutrients while at the same time degrading some antinutritional factors including InsP isomers. However, higher temperatures can compromise nutrient digestibility. In the current study, we concluded that the optimal temperature of extrusion is 110–115 °C.

Influence of endogenous estrogen on a network model of female brain integrity.

Recent reports document sex differences in midlife brain integrity and metabolic health, such that more relationships are detectable between metabolic syndrome (MetS) components and markers of brain health in females than in males. Midlife is characterized by a rapid decrease in endogenous estrogen levels for women which is thought to increase risk for cardiometabolic disease and neurocognitive decline. Our study used network models, designed to explore the interconnectedness and organization of relationships among many variables at once, to compare the influence of endogenous estrogen and chronological age on a network of brain and metabolic health in order to investigate the utility of estrogen as a biomarker for brain vulnerability. Data were analyzed from 82 females (ages 40-62). Networks consisted of known biomarkers of risk for late-life cognitive decline: the five components of MetS; Brain-predicted age difference calculated on gray and white matter volume; white matter hyperintensities; Default Mode Network functional connectivity; cerebral concentrations of N-acetyl aspartate, glutamate and myo-inositol; and serum concentrations of estradiol. A second network replaced estradiol with chronological age. Expected influence (EI) of estradiol on the network was -1.190, relative to chronological age at -0.524, indicating that estradiol had a stronger expected influence over the network than age. A negative expected influence indicates that higher levels of estradiol would be expected to decrease the number of relationships in the model, which is thought to indicate lower risk. Overall, levels of estradiol appear more influential than chronological age at midlife for relationships between brain integrity and metabolic health.

Dynamic changes in the chemical composition and metabolite profiles of drumstick (Moringa oleifera Lam.) leaf flour during fermentation

Solid-state fermentation (SSF) using mixed strains can increase the nutritional value and antioxidant content of Moringa oliefera Lam. leaf flour (MLF). However, little is known about the chemical composition and metabolite profiles of MLF during the fermentation process. In this work, mixed strains of Aspergillus Niger, Candida utilis and Bacillus subtilis were inoculated into MLF for SSF. The MLF's contents of crude protein (CP), crude fiber (CF), water soluble carbohydrate (WSC), reducing sugar, tannin and phytic acid all changed significantly as fermentation proceeded. A metabolomic analysis was performed using GC-TOF-MS, resulting in the identification of 347 metabolites. Fermentation with mixed strains significantly affected levels of amino acids, sugars, and organic acids; concentrations of most amino acids, oligosaccharides, organic acids, nucleosides, γ-aminobutyric acid (GABA), and myo-inositol were higher after 3 d of SSF than at the start. Additionally, several intermediate metabolites were detected in 3 d fermented MLF. The mixed microorganisms' metabolic activity thus seems to peak after 3 d of fermentation under the tested conditions. These results provide new insights into the changes in the chemical composition and metabolite content of MLF during SSF and reveal possibilities for producing valuable compounds via this process.

The trajectory of putative astroglial dysfunction in first episode schizophrenia: a longitudinal 7-Tesla MRS study

Myo-inositol is mainly found in astroglia and its levels has been shown to be reduced in the anterior cingulate cortex (ACC) of patients with schizophrenia. We investigate the status of astroglial integrity indexed by ACC myo-inositol at the onset and over the first 6 months of treatment of first episode schizophrenia. We employed 7 T magnetic resonance spectroscopy (1H-MRS) and quantified myo-inositol spectra at the dorsal ACC in 31 participants; 21 patients with schizophrenia with median lifetime antipsychotic exposure of less than 3 days, followed up after 6 months of treatment, and 10 healthy subjects scanned twice over the same period. We studied the time by group interaction for myo-inositol after adjusting for gender and age. We report significant reduction in myo-inositol concentration in the ACC in schizophrenia at an early, untreated state of acute illness that becomes insignificant over time, after instituting early intervention. This trajectory indicates that dynamic astroglial changes are likely to operate in the early stages of schizophrenia. MRS myo-inositol may be a critical marker of amelioration of active psychosis in early stages of schizophrenia.

SLC5A3 Transports Myo-Inositol to Support the Growth of Acute Myeloid Leukemia

Metabolic reprogramming contributes to tumor development and sustains cancer cell proliferation. Like other cancers, acute myeloid leukemia (AML), a devastating hematologic malignancy with poor overall survival, has altered metabolic features, providing new possibilities for AML treatment. Since the niche can reshape the metabolic properties of cancer cells, it is critical to validate AML metabolic vulnerabilities in a proper microenvironment. To this end, we optimized a protocol for CRISPR screening in orthotopic xenograft AML models, including patient-derived-xenograft (PDX) models tractable for CRISPR-editing, to enable the systematic evaluation of the physiological relevance of top AML dependencies. We performed in vivo screens in MV4-11 and U937 cell lines and a PDX model, which converged to reveal the sodium/myo-inositol cotransporter SLC5A3 as a top-ranked in vivo gene target.We have validated the SLC5A3 dependency in additional AML cell line and PDX models; SLC5A3 deletion consistently induced apoptotic cell death in all AML models tested. We also observed cell-context dependent alterations of cell cycle and differentiation. In addition, using a PDX model with a doxycycline-inducible CRISPR system, we have confirmed that induction of SLC5A3 knockout post transplantation significantly represses AML progression and prolonged mouse survival. Next, we investigated whether the growth defect caused by SLC5A3 knockout results from the myo-inositol deficiency. Augmentation of myo-inositol concentration in the standard culture medium completely rescued the proliferation of SLC5A3-knockout cells. In accordance, depletion of myo-inositol from the culture medium largely impeded the growth of parental AML cells, causing similar phenotypes as SLC5A3-deletion, with cell-context dependent alterations of cell cycle and induction of apoptotic cell death. Together, these data reveal that myo-inositol is a critical metabolite for AML.Since a subset of AML cell lines were not dependent on SLC5A3 based on a genome-scale CRISPR screen dataset (DepMap), we explored the potential biomarkers associated with SLC5A3 essentiality in AML. Intriguingly, the low expression of Inositol-3-phosphate synthase 1 (ISYNA1) predicted a strong SLC5A3 dependency in AML cell lines. In addition to importing myo-inositol from the extracellular fluid, cells can also synthesize myo-inositol de novo from glucose 6-phosphate, and ISYNA1 encodes the rate-limiting enzyme in this myo-inositol biosynthesis pathway. We confirmed low expression of ISYNA1 protein in AML cells sensitive to SLC5A3 deletion, and importantly, overexpression of ISYNA1 can completely relieve the SLC5A3 dependency. Moreover, knockout of ISYNA1 in an ISYNA1-high cell line M07e exacerbated the growth defect associated with SLC5A3 deletion. Altogether, these results strongly demonstrate that SLC5A3 becomes essential in AML cells with insufficient myo-inositol biosynthesis capacity to support AML proliferation.Finally, we have investigated the clinical features associated with low ISYNA1 expression in genomic datasets of primary AML samples, including TCGA and Beat AML, to postulate the patient population that can benefit from a SLC5A3-directed therapy. Interestingly, low ISYNA1 expression is associated with FAB M4 and M5 AML subtypes. In accordance, a monocyte lineage gene signature is enriched in ISYNA1-low samples. In addition, AML samples with low ISYNA1 expression tend to have IDH2 or DNMT3 mutations. Collectively, our study demonstrated that SLC5A3 is a strong metabolic dependency in AML, and targeting SLC5A3 can provide a therapeutic opportunity for a subset of monocytic AML. DisclosuresDharia: Genentech: Current Employment. Piccioni: Merck Research Laboratories: Current Employment. Stegmaier: AstraZeneca: Consultancy; KronosBio: Consultancy; Bristol Myers Squibb: Consultancy; Auron Therapeutics: Consultancy, Current equity holder in publicly-traded company; Novartis: Research Funding.

A COMPARISON OF METABOLITES IN WOOD-FORMING TISSUES FROM EIGHT COMMERCIAL TIMBER TREE SPECIES OF HEILONGJIANG PROVINCE IN CHINA

Four coniferous and four deciduous commercial tree species from Northeastern ofChina were selected to investigate the differences ofmetabolites in wood-forming tissues bygas chromatography-mass spectrometry. The results showed that the identified metabolites mainly consisted of neutral sugars, lipids, and organic acids. The mean contents of both arabinofuranose and 1-cyclohexene-1-carboxylic acid were higher in coniferous trees thanin deciduous ones. Similarly, the D-fructose and D-glucose content was significantly higherin coniferous trees than deciduous trees, but the total contents of these two sugars was roughly equal among most tree species. The mean content of lactic acid, glycerol and malic acid was lowerin coniferous trees than deciduous trees. The malic acid content decreased in later-stages of wood formation than in early-stagefor all tree species. The content of L-proline and myo-inositol was greater in later-stage of wood formation than early-stage.The contentof octadecanoic acid, D-fructose and D-glucose decreased in later-stage of wood formationfor most tree species. All of thissuggested that the metabolites in wood-forming tissues showed the significance of species-specific and seasonal dynamic differences among the eight tree species.

Phosphorus digestibility and phytate degradation in pigs fed wheat-based diets with different intrinsic phytase activity and added microbial phytase

ABSTRACT The objective of this study was to investigate the effect of variation in wheat-derived phytase activity on myo-inositol 1,2,3,4,5,6-hexakis (dihydrogen phosphate) (InsP6) degradation, inositol phosphate (InsP) isomer concentration and phosphorus (P) digestibility in pigs fed wheat-based diets. Additional effects of a microbial phytase supplementation were also studied. Three wheat genotypes (W1-W3) with an analysed phytase activity between 2760 and 3700 FTU/kg were used to formulate four experimental diets that included soybean meal and rapeseed meal but did not contain a mineral P supplement. DietW1-DietW3 only differed in the included wheat genotypes (W1-W3) at an inclusion level of 400 g/kg. DietW3+ contained W3 and a commercial 6-phytase supplementation at 500 FTU/kg diet. Eight barrows with an initial body weight of 27 kg were fitted with a simple T-cannula at the distal ileum and assigned to the four dietary treatments in a completely randomised row column design. The experiment included four periods of 12 d each. The first 5 d of each period were for diet adaptation, followed by collection of faeces (4 d), ileal digesta (2 d), and blood (last day). In DietW1-DietW3, the mean precaecal (pc) InsP6 disappearance was 48% and the mean pc P digestibility was 37% without a significant effect of the wheat genotype. The InsP6 disappearance measured in the faeces was close to complete in all treatments, and faecal P digestibility was not significantly affected by the wheat genotype (36% overall). The addition of microbial phytase caused a significant increase in pc InsP6 degradation (to 79%) and pc and total tract P digestibility (to 53% and 52%, respectively). The concentration of InsP6 degradation products in ileal digesta was not significantly affected by the wheat genotype, except for that of Ins(1,2,3,4,6)P5 and myo-inositol, which were higher in DietW3 than in DietW1 and DietW2. The added microbial phytase significantly reduced the concentration of InsP5 isomers in the ileal digesta and increased the concentrations of lower InsP isomers and myo-inositol. There were no significant effects of the added microbial phytase on pc amino acid digestibility; however, the wheat genotype exerted significant effects on the pc digestibility of Cys, Gly and Val. It was concluded that an increase in the intrinsic phytase activity of wheat achieved by crossbreeding was not reflected in InsP6 degradation and P digestibility in pigs fed wheat-based diets.

Abnormal neurobiochemical metabolites in the first- episode schizophrenia and clinical high-risk population.

To explore the metabolite characteristics in medial prefrontal cortex (mPFC) by 1H magnetic resonance spectroscopy (1H-MRS) in the first-episode schizophrenia (FES) and clinical high-risk (CHR) people. A total of 46 patients with the first-episode schizophrenia (FES), 49 people with clinical high risk (CHR), 61 people with genetic high risk (GHR), and 58 healthy controls (HC) were enrolled. The levels of N-acetylaspartylglutamate+N-acetylaspartate (tNAA), choline-containing compounds (Cho) and myo-inositol (MI), glutamate+glutamine (Glx) in medial prefrontal cortex were measured by single-voxel 1H-MRS. The clinical symptoms were evaluated in the FES group and the CHR group. Continuous performance test (CPT) were carried out to assess the visual and auditory accuracy and reaction time in the 4 groups. There were significant differences in Glx, tNAA, and MI concentrations among 4 groups (all P<0.05). Compared with the HC group, the FES group showed lower level of MI and Glx. The levels of Glx and tNAA in the CHR group were significantly lower than those in the GHR group (all P<0.05). The visual and auditory accuracies of CPT in the FES group were significantly lower than those in the HC group (P<0.05). In the FES group, Glx was negatively correlated with the reaction time of vision (r=-0.41, P=0.05). The decreased levels of MI and Glx in the FES patients suggest that there may be glial functional damage and glutamatergic transmitter dysfunction in the early stage of the disease. The compensatory increase of metabolites may be a protective factor for schizophrenia in the genetic individuals.

Serum metabolites associated with increased insulin resistance and low cardiorespiratory fitness in overweight adolescents

Background and aimsObesity affects metabolism, increasing the risk of developing non-communicable diseases in adolescence, due to excess adipose tissue and low cardiorespiratory fitness (CRF). The metabolomics approach allows the elucidation of metabolites, which may have the concentrations altered by several factors, such as body composition (BC). We aimed to analyze the metabolomic profile of normal-weight and overweight adolescents and associate the metabolites with clinical markers related to BC, insulin resistance (IR), and CRF. Methods and resultsThe sample was composed of 57 adolescents and divided into two groups: the normal-weight group (NWG, n = 24) and the overweight group (OWG, n = 33). They underwent blood collection and anthropometric, BC, and CRF assessment. Blood serum samples were analyzed by 1H-NMR spectroscopy (600 MHz). The OWG presented higher values of body weight (BW), body mass index (BMI), waist circumference (WC), fasting glucose, insulin, IR, cholesterol, and percentage of fat mass (%FM) and lower levels of peak oxygen consumption (VO2 peak) compared with the NWG. The OWG presented lower concentrations of 3-hydroxyisovalerate, glutamate, and methionine as well as higher concentrations of aspartate, asparagine, creatine, glycerol, myo-inositol, proline, pyruvate, tyrosine, and valerate compared with the NWG. The concentrations of glutamate, myo-inositol, creatine, methionine, and valerate correlated with %FM; pyruvate and valerate positively correlated with IR; and glutamate, tyrosine, and valerate negatively correlated with CRF. ConclusionChanges in the BC lead to changes in the metabolomic profile of adolescents, and the altered metabolites are associated with increased IR and low CRF. These results indicate new targets for health monitoring and prevention of cardiovascular and metabolic diseases in adolescents.

Evaluation of the Activity of Prostate Cancer Biomarkers in Post-massage Urine

Evaluation of the Activity of Prostate Cancer Biomarkers in Post-massage Urine

Determination of myo-inositol content in milk by high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD)

A method to determine inositol content in milk using high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) was developed and validated. Samples were hydrolyzed with 10 mL HCl in a vacuum oven at 120oC, prolonging 6 h. Hydrolyzed samples were neutralized to a pH from 6 to 7.5 before analysing in an HPAEC-PAD system. The analytical program used Dionex CarboPacTM&amp;nbsp;MA1 column (4 &amp;times; 250 mm) with a mobile phase of a gradient program including NaOH 50 mM and NaOH 1M. The method was validated following AOAC guidelines: selectivity, linear range from 0,01 to 20 mg/L with&amp;nbsp;a coefficient (R) 0.9998, the recoveries in the range of 99 - 102%, and repeatability with RSD under 1.8%. The limit of detection (LOD) and the limit of quantification (LOQ) of inositol were 0.047 &amp;micro;g/g and 0.155 &amp;micro;g/g, respectively. The method has been applied to determine of inositol content in milk samples with content ranging from 22.5 mg/100g to 64.7 mg/100g.

A magnetic resonance imaging study in etiology of nonobstructive azoospermia.

Testicular magnetic resonance imaging parameters, including apparent diffusion coefficient, fractional anisotropy, magnetization transfer ratio, and normalized metabolite concentrations represent useful noninvasive fingerprints of nonobstructive azoospermia. Nonobstructive azoospermia etiology might correlate with the spermatogenesis status. To assess the possible association between apparent diffusion coefficient, fractional anisotropy, magnetization transfer ratio, and normalised metabolite concentrations with nonobstructive azoospermia etiology. This retrospective study included 48 consecutive men with nonobstructive azoospermia and 18 age-matched controls. All participants underwent scrotal magnetic resonance imaging. The testicular apparent diffusion coefficient, fractional anisotropy, magnetization transfer ratio, and normalized metabolite concentrations were calculated. nonobstructive azoospermia men were classified into three groups, based on etiology: group 1, idiopathic; group 2, genetic causes; and group 3, non-genetic causes. Parametric and nonparametric statistical tests were used to evaluate differences in magnetic resonance imaging parameters between nonobstructive azoospermia groups and normal testes (group 4). Regression analysis was performed to assess the most predictive magnetic resonance imaging factor of nonobstructive azoospermia etiology. Differences in mean apparent diffusion coefficient (p<.001), fractional anisotropy (p<.001), magnetization transfer ratio (p<.001), and normalized concentrations of total choline (p=.005), glucose (p=.012), myo-inositol (p=.024), and lipids (p=.010) were observed among groups. Regression analysis failed to identify the most discriminating magnetic resonance imaging feature for nonobstructive azoospermia etiology. Apparent diffusion coefficient, fractional anisotropy, magnetization transfer ratio, and normalized concentrations of total choline, glucose, myo-inositol, and lipids are helpful in discriminating nonobstructive azoospermia etiology. Magnetic resonance imaging may provide useful, noninvasive information on the microstructural and biochemical milieu of nonobstructive azoospermia testes.