Diagnostic Models for Screening of Periodontitis with Inflammatory Mediators and Microbial Profiles in Saliva.

This study aims to investigate and assess salivary biomarkers and microbial profiles as a means of diagnosing periodontitis. A total of 121 subjects were included: 28 periodontally healthy subjects, 24 with Stage I periodontitis, 24 with Stage II, 23 with Stage III, and 22 with Stage IV. Salivary proteins (including active matrix metalloproteinase-8 (MMP-8), pro-MMP-8, total MMP-8, C-reactive protein, secretory immunoglobulin A) and planktonic bacteria (including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas nigrescens, Parvimonas micra, Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens, Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Actinomyces viscosus) were measured from salivary samples. The performance of the diagnostic models was assessed by receiver operating characteristics (ROCs) and area under the ROC curve (AUC) analysis. The diagnostic models were constructed based on the subjects' proteins and/or microbial profiles, resulting in two potential diagnosis models that achieved better diagnostic powers, with an AUC value > 0.750 for the diagnosis of Stages II, III, and IV periodontitis (Model PA-I; AUC: 0.796, sensitivity: 0.754, specificity: 0.712) and for the diagnosis of Stages III and IV periodontitis (Model PA-II; AUC: 0.796, sensitivity: 0.756, specificity: 0.868). This study can contribute to screening for periodontitis based on salivary biomarkers.

Metabolomic signatures in peripheral blood associated with Alzheimer's disease amyloid-ß-induced neuroinflammation.

Discovery of biomarkers in peripheral blood is a crucial step toward the early diagnosis and repetitive monitoring of treatment response for Alzheimer's disease (AD). Metabolomics is a promising technology that can identify unbiased biomarkers. To explore potential blood biomarkers for AD via metabolic profiling with high-resolution magic angle spinning nuclear magnetic resonance techniques, we identified changes in peripheral blood metabolomic profiles in response to amyloid-ß (Aß)-induced neuroinflammation and co-treatment with gallate, a phytochemical known to have anti-neuroinflammatory properties. Alzheimer's-like (AL) model mice were produced by intracerebroventricular infusion of Aß and compared with normal control mice with infusion of vehicle. AL mice were treated with either gallate (treated AL mice) or vehicle (untreated AL mice). Metabolomic analyses of both whole blood and plasma showed a clear separation between untreated AL mice and the other two groups, with levels of several metabolites involved in energy metabolism, including pyruvate and creatine, being significantly reduced in untreated AL mice compared with control and treated AL mice. Gallate treatment suppressed Aß-induced overproduction of the inflammatory cytokine tumor necrosis factor-α in the hippocampus and normalized plasma levels of the affected metabolites. These results suggest that plasma levels of several metabolites could be indicative of both brain pathology and therapeutic responses, supporting the possibility of a close relationship between central neuroinflammation and systemic metabolic disturbance. These findings also suggest the potential of NMR-based metabolomics as a method to identify novel plasma biomarkers for AD, which could be confirmed by future translational research with human patients.

Assessment of peeling of Astragalus roots using 1H NMR- and UPLC-MS-based metabolite profiling.

A metabolomic analysis was performed to examine the postharvest processing of Astragalus membranaceus roots with a focus on the peeling procedure using (1)H NMR and UPLC-MS analyses. Principal component analysis (PCA) score plots from the (1)H NMR and UPLC-MS data showed clear separation between peeled and unpeeled Astragalus roots. Peeled roots exhibited significant losses of several primary metabolites, including acetate, alanine, arginine, caprate, fumarate, glutamate, histidine, N-acetylaspartate, malate, proline, sucrose, trigonelline, and valine. In contrast, the peeled roots contained higher levels of asparagine, aspartate, and xylose, which are xylem-related compounds, and formate, which is produced in response to wound stress incurred during postharvest processing. In addition, the levels of isoflavonoids and astragalosides were significantly reduced in peeled Astragalus root. These results demonstrate that metabolite profiling based on a combination of (1)H NMR and UPLC-MS analyses can be used to evaluate peeling procedures used in the postharvest processing of herbal medicines.

Urinary ketone is associated with the heart failure severity.

OBJECTIVES: To test the hypothesis that urinary metabolites characterizing heart failure (HF) are associated with the magnitude of echocardiographic measurements and ultimately the severity of HF. DESIGN/METHODS: Patients with systolic HF (n=46) and control subjects (n=32) participated in this study. Patients with type 2 diabetes mellitus were excluded. Echocardiographic measurements were performed, and selected urinary metabolites were quantified. RESULTS: Urinary levels of acetate (p<0.05), acetone (p<0.01), cytosine (p<0.001), methylmalonate (p<0.001), and phenylacetylglycine (p<0.01) were significantly higher, while 1-methylnicotinamide (p<0.05) were significantly lower in HF patients than in controls. There were significant differences in E/E' (p<0.05), urinary levels of acetate (p<0.005), acetoacetate (p<0.05), acetone (p<0.05) and ketones (p<0.01) according to the New York Heart Association (NYHA) classification in HF patients. Multiple linear regression analysis revealed that urinary ketones were found to be independent factors for both left ventricular ejection fraction and E/E' after adjusting for confounders. CONCLUSION: Our results showed that urinary levels of ketone bodies are associated with the magnitude of echocardiographic parameters.

1H NMR-based metabolite profiling of diet-induced obesity in a mouse mode.

High-fat diets (HFD) and high-carbohydrate diets (HCD)- induced obesity through different pathways, but the metabolic differences between these diets are not fully understood. Therefore, we applied proton nuclear magnetic resonance ((1)H NMR)-based metabolomics to compare the metabolic patterns between C57BL/6 mice fed HCD and those fed HFD. Principal component analysis derived from (1)H NMR spectra of urine showed a clear separation between the HCD and HFD groups. Based on the changes in urinary metabolites, the slow rate of weight gain in mice fed the HCD related to activation of the tricarboxylic acid cycle (resulting in increased levels of citrate and succinate in HCD mice), while the HFD affected nicotinamide metabolism (increased levels of 1-methylnicotineamide, nicotinamide-N-oxide in HFD mice), which leads to systemic oxidative stress. In addition, perturbation of gut microflora metabolism was also related to different metabolic patterns of those two diets. These findings demonstrate that (1)H NMR-based metabolomics can identify diet-dependent perturbations in biological pathways.

Metabolic profiling of an alcoholic fatty liver in zebrafish (Danio rerio).

Zebrafish (Danio rerio) is becoming a popular developmental biology model to study diseases and for drug discovery. In this study, we performed proton nuclear magnetic resonance spectroscopy ((1)H-NMR)- and gas chromatography-mass spectrometry (GC/MS)-based metabolic profiling of an alcoholic fatty liver using a zebrafish disease model. We examined metabolic differences between the control and alcoholic fatty liver groups in zebrafish to determine how metabolism in an alcoholic fatty liver is regulated. Multivariate statistical analysis showed a significant difference between the control and alcoholic fatty liver groups. The alcoholic fatty liver group showed increased excretion of isoleucine, acetate, succinate, choline, creatine, acetoacetate, 3-hydroxybutyrate (3HB), ethyl glucuronide (EtG), lactate/pyruvate ratio, fatty acids, and cholesterol, and decreased excretion of citrate, aspartate, tyrosine, glycine, glucose, alanine, betaine, and maltose. Metabolites identified in the fatty liver groups were associated with long-term alcohol consumption, which causes both oxidation-reduction (redox) changes and oxidative stress. This study suggests that global metabolite profiling in a zebrafish model can provide insights into the metabolic changes in an alcoholic fatty liver.