Метаболомика:Открытый доступ

Background: Although many studies have demonstrated that plasma metabolic phenotyping allows discriminating between cancer patients and controls, it remains unclear whether different cancer types elicit distinguishable metabolic signatures. Therefore, the present study was designed to examine whether metabolic phenotyping of blood plasma by proton nuclear magnetic resonance spectroscopy allows discriminating between 37 colorectal cancer, 37 breast cancer and 37 lung cancer patients. Material and methods: Plasma proton nuclear magnetic resonance spectra were rationally divided into 110 integration regions defined on the basis of spiking experiments with known metabolites. The normalized integration values of these 110 regions, which represent the metabolic phenotype, were used as statistical variables to construct a classification model which enables to discriminate between the three aforementioned cancer types. Results: The resulting model allows classifying 78% of the colorectal cancer patients, 95% of the breast cancer patients and 84% of the lung cancer patients correctly. Conclusion: This preliminary feasibility study provides strong indications that the plasma metabolic phenotype has potential to become a complementary diagnostic tool to differentiate between cancer types in addition to known general cancer biomarkers.

Since suicide is a causality of a lot of human mortalities worldwide, its therapeutic study is of great medical significance. Yet human suicide predictions and preventions are still difficult until now. As a result, it needs to find out new ways of solving this dilemma. As human suicide etiological/pathologic undertaking is quite necessary, human suicide treatments can be better transformed from clinical symptom observations into new generations of therapeutics-mental illness-related diagnostics and therapeutics. In future, better clinical suicide predictions, preventions and therapeutic managements can be established via pathways of human mental illness studies.

Glutathione-S-Transferase (GST) genes, including GSTT1, GSTP1, and GSTM1, play a major role in detoxification and metabolism of xenobiotics. The aim of the present study was to test an orally bioavailable GSH-based compound in poor detoxifier subjects regarding their oxidative stress, ammonia metabolism and heavy metal clearance. Eligibility was established with a telephone questionnaire followed by a clinical examination to obtain height, weight, blood pressure and screening blood chemistry and GSTM-1 gene test. Seventy-five GSTM1-null, non-smoking healthy individuals were introduced in the study who were teetotallers or were using a maximum of 20 g alcohol/day men (n = 47) and women (n = 28) aged 38-69 years (mean: 49.7) with body-mass index ranging from 22 to 29 kg/m2) participated in the study. All enrolled participants were free from acute or chronic diseases and did not eat a diet or take medications that might interfere with outcome markers namely antioxidant supplements, high intake of dietary polyphenols including coffee, grapefruit juice or anti-inflammatory medications. Subjects were divided in 3 groups (25 subjects each): a) Given an oral bioabsorbable glutathione-based compound added with selenium, L-cysteine and vitamin C (GLU-9599, Named Research Co., Lesmo, Italy) at the dosage of 1 tab a day for two months; b) 600 mg of glutathione in 250 saline, given intravenously over 90 min, twice a week for 2 months; and c) Given 3 g a day of a strong cation-exchange oral chelator consisting of a mixture of chabasite-phillipsite for two months. Dietary questionnaire was administered to all subjects. Either at baseline, at one month or at the end of the study the following parameters were tested: erythrocytes (RBC) level of GSH/GSSG and Glutathione Peroxidise (GPx), urinary 8-OHdG, 24 h urinary measurement of main heavy metals, faecal metals, ammonia and oxidative stress. GLU-9599 showed to significantly lower either RBC oxidative stress or urinary 8-OHdG as compared to either IV glutathione or oral chelator (p<0.01). There was a significant correlation between urinary 8-OHdG and overall heavy metal excretion (r: 0.58, p<0.005) but no correlation occurred with RBC oxidative stress. Few subjects with fatty liver and abnormal transaminases improved their value during treatment with GLU-9599. Only oral chelator was effective in significantly lower faecal metals, ammonia and faecal oxidative stress (p<0.005). There was a not significant trend increase of mercury faecal excretion and GLU-9599. Overall, it would appear that in poor-detoxifier (GSTM1-null genotype) subjects, an effective orally-absorbable stabilised-glutathione can efficiently restore antioxidant defences in view of a potential wider application as an integrative adjuvant co-treatment in patients environmentally-exposed and also under pharmacological burden. Effective heavy metal clearance remains a still unresolved issue which may benefit from the rational addition of high cation-exchange oral chelators with a likely association with viable glutathione supplements too.

A universal molybdenum-containing cofactor is necessary for the activity of all eukaryotic molybdoenzymes. In humans four such enzymes are known: Sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase and a mitochondrial amidoxime reducing component. Of these, sulfite oxidase is the most important and clinically relevant one. Mutations in the genes MOCS1, MOCS2 or GPHN - all encoding cofactor biosynthesis proteins - lead to molybdenum cofactor deficiency type A, B or C, respectively. All three types plus mutations in the SUOX gene responsible for isolated sulfite oxidase deficiency lead to progressive neurological disease which untreated in most cases leads to death in early childhood. Currently, only for type A of the cofactor deficiency an experimental treatment is available.

intervention strategies. The mammalian Target of Rapamycin (mTOR) is a conserved kinase and master regulator of metabolism and cell growth. mTOR is dysregulated in diabetes and pancreatic cancer. Recent reports indicate that 50% of Pancreatic Ductal Adenocarcinoma (PDAC) patients are diabetic at the time of diagnosis. Furthermore, the anti- diabetic drug, metformin, which indirectly inhibits mTOR, has emerged as a potential therapeutic target for PC.

The objective of this study is to determine the targeted-metabolomics profile in PDAC cell line (HPAF-II) with mTOR inhibition and that interaction between mTOR ATP-competitive inhibitor (Torin 2) and metformin as potential combined therapy in PC.

HPAF-II cell lines were cultured in the presence of either Torin 2, metformin, both, or control vehicle. We utilized targeted LC/MS/MS to characterize the alterations in glycolytic and tricarboxylic acid cycle metabolomics, and employed Western Blot analysis for cell signaling activation by phosphorylation. Comparisons between groups were analyzed using one-way Analysis of Variance followed by secondary post-hoc analysis.

After 1 h incubation with metformin, AMP concentration was significantly increased compared to other groups (p<0.03). After 24 h, Torin-2 significantly decreased glycolysis intermediates (fructose 1,6-bisphosphate (FBP), and 2-phosphoglycerate/3-phosphoglycerate), TCA intermediate metabolites (citrate/isocitrate, and malate), as well as Nicotinamide Adenine Dinucleotide (NAD+) and Flavin Adenine Dinucleotide (FAD), and ATP levels. When HPAF-II cells were incubated with both Torin-2 and metformin, there was a significant reduction in NAD+ and FAD, suggesting decreased levels of the energy equivalents that are available to the electron transport chain.

Targeted metabolomics data indicate that mTOR complexes inhibition by Torin 2 reduced glycolytic intermediates and TCA metabolites in HPAF- II and may synergize with metformin to decrease the electron acceptors NAD+ and FAD which may lead to reduced energy production.

Plant Growth-Promoting Rhizobacteria (PGPR) enhances host plant growth and tolerance to biotic and abiotic stresses. Despite increased knowledge of their functional activities, reports of their impact on host metabolism and signalling networks are rare. In this study, small organic substances were analysed in the ascending xylem sap of maize plantlets that were inoculated with the PGPR Azospirillum lipoferum. In this feasibility study, xylem sap collection using a Scholander chamber was combined with metabolome analysis by Gas Chromatography-Mass Spectrometry (GC-MS) based profiling. Two genotypes of maize were investigated. Cultivar Seiddi displayed A. lipoferum-mediated increases in lateral root growth and enhanced photosynthetic potential unlike non-responsive cultivar FuturiXX. A total of 119 small organic substances were annotated in maize xylem sap. The content of 17 substances, including primary metabolites, such as sucrose, maltose, glucose, TCA cycle intermediates, amino acids, GABA and shikimate pathway metabolites, decreased in both cultivars after A. lipoferum inoculation and may thus reflect general effects of the maize-A. lipoferum interaction. The content of 28 additional substances, namely glucose, lactic acid, acidic intermediates of the pentose phosphate and ascorbate/aldarate pathways and defense-related hydroxycinnamic acids, specifically changed in the xylem sap of the A. lipoferum-phytostimulated cultivar Seiddi, therefore, suggesting that phytostimulation of maize by A. lipoferum may involve xylem-transported metabolic signalling. Glucose or other metabolites that are retrograde transported through the xylem to the shoot by transpirational pull may act as feedback signals of the root status. Such signals may stimulate leaves to enhance photosynthesis-mediated C-assimilation that is needed to sustain A. lipoferum-triggered root growth. The untargeted metabolome analysis of the xylem, i.e., the xylenome, indicates that the differential interactions of the two maize cultivars Seiddi and FuturiXX with Azospirillum lipoferum could represent a feasible system for the study of the role of xylem transported signals in plant/ PGPR interactions.

More recently, it has been gradually recognized that natural chemical drugs often exhibit higher therapeutic efficacy and lower toxicities than synthetic drugs in most disease managements and therapeutics. After this discovery, growing attentions have been focused on this type of drug development chain updating worldwide. Yet, these kinds of pharmacological efforts still like finding a needle from hay-stakes owing to drug screening system limitations globally. As a result, higher efficient drug screening routines must be established-including new generations of experimental models, quick plant chemical discovery processes structurally and extractive quality, revisit from ancient wisdoms, especially from traditional Chinese medicine. This article addresses this matter in detail and future perspectives.

Background: The aims of the study were to evaluate glycemic, insulinemic, lipidemic and antioxidant properties of C. arietinum in neonatal-streptozotocin (nSTZ) rats.

Materials and methods: Seeds were collected from the commercially available sources of Dhaka city, identified from Bangladesh National Herbarium and absolute ethanol extract was prepared. A single iv injection of STZ were given to neonate rats of Long Evans strain and 12 weeks later an OGTT was done and rats with fasting glucose level above 7.5 mmol/L were selected. The rats were divided into four groups: i) Water control, ii) Glibenclamide (5 mg/kg bw), iii) C. arietinum 0.625 g/kg bw (CA Ext 1) and iv) 1.25 g/kg bw (CA Ext 2) treated. Body weight was measured weekly. Blood was collected by cutting the tail tip on 0 day and by decapitation on 28 day. Fasting serum glucose, insulin, lipid profiles, creatinine, ALT, MDA, GSH, hepatic glycogen were measured. HOMA B% and HOMA S% were calculated. The data were analyzed using appropriate tools.

Results: A significant decrease of fasting glucose level was noticed on 28 day with CA Ext 2 compared to baseline (p<0.05); 26% and 18% decrease were found in comparison to water and glibenclamide treated groups respectively. Blood glucose lowering effect was associated with insulin lowering effect of CA Ext 2. Treatment with CA Ext 2 improved HOMAB%, and both treated groups improved HOMA IR of nSTZ diabetic rats. Total cholesterol was significantly decreased in comparison to water control on 28 day (p=0.014); triglycerides decreased by 11% and HDL increased by 4% respectively in CA Ext 2 group. Serum ALT and creatinine levels were remained unchanged by C. arietinum. A significant increase of reduced-GSH level was found in CA Ext 1 treated group (p=0.031).

Conclusion: CA Ext 2 showed significant hypoglycemic and antilipidemic effects most likely through decreasing insulin resistance and improving insulin sensitivity. It also has antioxidant activity that reduces the oxidative changes induced by STZ administration.