Metabolomics study of cereal grains reveals the discriminative metabolic markers associated with anatomical compartments

This study used NMR-based metabolomics to compare the metabolic profile of different anatomical compartments of cereal grains i.e. bran and endosperm in order to gain further insights into their possible role in the beneficial health effects of whole grain products (WG). Polar water-soluble metabolites in 64 bran and endosperm, samples from rye and wheat were observed using 600 MHz NMR. Bran samples had higher contents of 12 metabolites than endosperm samples. A comparative approach revealed higher contents of azelaic acid and sebacic acid in bran than in endosperm. In a pilot study, the consumption of WG rye bread (485 g) caused NMR signals in 24h urine corresponding to azelaic acid. The relatively high abundance, anatomical specificity, pattern of metabolism, urinary excretion in human, antibacterial, and anticancer activities suggest further studying of azelaic acid when exposure to WG or beneficial effects of WG are investigated

Oral metronidazole as antibiotic prophylaxis for patients with nonperforated appendicitis

Hassan Ravari1, Ali Jangjoo2, Jalal Motamedifar2, Kasra Moazzami31Vascular and Endovascular Surgery Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 2Department of General Surgery, Mashhad University of Medical Sciences, Imam Reza Hospital, Mashhad, 3Department of General Surgery, Tehran University of Medical Sciences, Sina Hospital, Tehran, IranBackground: The rate of wound infection after appendectomy without antibiotic prophylaxis is 10%–30%. The role of prophylactic antibiotic therapy in nonperforated appendicitis is still controversial. Metronidazole is against anaerobic organisms and its bioavailability after oral and parenteral administration has been shown to be similar. The objective of the present study is to compare the infective complications rate after open appendectomy for nonperforated appendicitis receiving either oral or intravenous metronidazole as prophylaxis. Methods and Materials: From June 2007 to July 2009 in a randomized controlled trial, 204 patients with nonperforated appendicitis underwent an open appendectomy; 122 male and 82 female with mean age of 25 years. Among these, 102 (case group) received oral metronidazole and in 102 (control group) metronidazole was administered intravenously before surgery. The rate of wound infection and duration of the postoperative hospital stay was studied in the two groups.Results: The rate of wound infection was not significantly different in the two groups. (6% and 4% in study and control group, respectively, P = 0.861). Also the hospital stay was equal in two groups (2.3 days and 2.7 days in study and control group, respectively, P = 0.293).Conclusion: Single dose of oral metronidazole prior to operation can provide a sufficient prophylaxis for nonperforated appendicitis; so, it can be substitute the parental route of antibiotic administration. Keywords: antibiotic prophylaxis, wound infection, appendectomy, complication

A Histological Comparison of a New Pulp Capping Material and Mineral Trioxide Aggregate in Rat Molars

Introduction: Recent investigations have attempted to improve regenerative endodontics with the help of stem cell therapy. In vitro studies have shown the ability of different agents to stimulate the differentiation of dental pulp stem cells (DPSC) into odontoblast-like cells. A combination of dexamethasone, β-glycerophosphate and Vitamin D has been proven to induce a successful differentiation. The aim of this animal study was to evaluate the effect of this combination, named odontoblastic differentiating material (ODM), on pulp tissue when used as a capping material. Materials and Methods: Sixty maxillary right and left molars of 30 Sprague-dawley rats were selected for this study. The teeth were exposed under sterile condition. Half of the teeth were capped with mineral trioxide aggregate (MTA) and the other half with ODM. All cavities were restored with glass ionomer. The rats were sacrificed at post-operative intervals of 2 weeks and 2 months. Samples were histologically evaluated for the degree of inflammation and reparative dentin formation. Finally the data was analyzed with Mann-Whitney and Chi-Square tests. Results: Reparative dentin formed in all groups within both time periods and there was no statistically significant difference between the groups in the mentioned time periods. The MTA group, however, showed a statistically significant reduction in inflammation at both time intervals (P<0.05). Compared to MTA, ODM samples showed a greater amount of inflammation in the pulp tissue. Conclusion: ODM, as a pulp capping material, can induce dentinal bridge formation

Učinak kratkotrajne primjene hormona rasta i treninga snage na histopatološke promjene tkiva štitnjače i mutaciju gena BRAF (T1799A) u smeđeg štakora (Rattus norvegicus)

High levels of growth hormone accelerate mitosis rate but decrease the apoptosis process in its target organs. These events might cause the initiation of different cancer types. Thus, the main aims of this study were assessing the effects of short term growth hormone administration and resistance training on the histopathology and detection of the BRAF-V600E mutation in the thyroid tissue of male Rattus norvegicus brown rats. Thirty-two rats were randomly divided into four groups. After 8 weeks of the experiment (i.m), thyroid tissue and blood samples of saline (CS), resistance training+saline (RS), growth hormone (2 mg/kg) (GI) and resistance training+growth hormone (2 mg/kg) (RG) were taken to evaluate histopathology, the BRAF T1799A mutation of thyroid tissue, and circulating levels of IGF-1 and IGFBP-3. The protocol of training consisted of rats climbing a ladder while carrying weights (3 sets/5 reps). Microscopic evaluation of thyroid tissue did not show any histopathological changes, and there were no mutations in the studied region of the BRAF sequence. Serum IGF-1 concentration was significantly lower in the RS group than in other groups (P<0.05). However, serum IGFBP-3 concentration did not change significantly in the RS group. Moreover, serum IGF-1 and IGFBP-3 concentrations were significantly higher in the GI and RG groups than in the others (P<0.05). In conclusion, the decrement of serum IGF-1 concentration and IGF-1/IGFBP-3 ratio after resistance training might decrease the risk of cancer. Furthermore, short term growth hormone administration, with and without resistance training, might increase the risk of cancer through the high levels of serum IGF-1 concentration and IGF-1/ IGFBP-3 ratio in male rats.Visoke razine hormona rasta povećavaju brzinu mitoze, ali smanjuju proces apoptoze u ciljnim organima, što može uzrokovati nastanak različitih tipova raka. Stoga je glavni cilj ovoga istraživanja bio utvrditi učinak kratkotrajne primjene hormona rasta i treninga snage na histopatološke promjene tkiva štitnjače i nalaz mutacije gena BRAF-V600E u mužjaka smeđeg štakora Rattus norvegicus. Ukupno 32 štakora nasumično su podijeljena u četiri skupine koje su ovisno o primjenjenom tretmanu označene kao CS (fiziološka otopina), RS (trening snage + fiziološka otopina), GI (hormone rasta, 2 mg/kg) i RG (trening snage+hormone rasta, 2 mg/kg). Nakon osam tjedana pokusa (i.m.) uzeti su uzorci tkiva štitnjače i uzorci krvi kako bi se procijenila histopatološka svojstva, mutacija BRAF T1799A tkiva štitnjače te razine cirkulacijskog IGF-1 i IGFBP-3. Trening se sastojao od toga da se štakori penju ljestvama noseći težinu (3 seta vježbi, 5 ponavljanja). Mikroskopska procjena tkiva štitnjače nije pokazala histopatološke promjene i nije bilo mutacija u promatranoj regiji sekvencija gena BRAF. Koncentracija serumskog IGF-1 bila je znakovito manja u skupini RS nego u ostalim skupinama (P < 0,05), no u toj skupini nije bilo znakovite promjene u koncentraciji serumskog IGFBP-3. Štoviše, koncentracije serumskog IGF-1 i IGFBP-3 bile su znakovito veće u skupinama GI i RG nego u ostalim skupinama (P < 0,05). Stoga smo zaključili da bi smanjenje koncentracije serumskog IGF-1 i IGF-1/IGFBP-3 nakon treninga snage moglo smanjiti rizik od raka. Osim toga kratkotrajna primjena hormona rasta, s treningom snage kao i bez njega, mogla bi povećati rizik od raka povećavajući koncentracije serumskog IGF-1 i IGF-1/IGFBP-3 u mužjaka štakora

Cadmium Reduction in Spring Wheat: Root Exudate Composition Affects Cd Partitioning Between Roots and Shoots

Cadmium (Cd) in cereals is one of the major sources of Cd intake by human diets, and solutions to reduce Cd concentrations in wheat still need to be developed. Plant breeding, by selecting low-Cd varieties, can be an important tool to reduce Cd in crops. Knowing the genotypic variation in Cd accumulation and furthering our understanding of the impact of root exudates composition on Cd accumulation in crops may provide valuable information for plant breeding. In this study, we selected nine spring wheat varieties and analysed the accumulation and distribution of Cd in shoots, roots, root surfaces and kernels in relation to their qualitative and quantitative composition of root exudates, determined by H-1-NMR (Proton Nuclear Magnetic Resonance). Results showed that the Cd concentration in shoots at an early stage could be used as a predictor for Cd concentration in kernels. Total Cd uptake was not correlated to the mobility of Cd in the rhizosphere, but total Cd was negatively correlated to Cd adsorbed at the root surface. Furthermore, (i) exudation of organic acids (primarily succinate and acetate) increased Cd concentration in shoots, and (ii) exudation of nucleosides, DNA (deoxyribonucleic acid) degradation products, increased Cd adsorption at the root surface. Therefore, root exudates composition should be taken into account when selecting for low-Cd wheat traits

Oleaginous yeast Rhodotorula toruloides biomass effect on the metabolism of Arctic char (Salvelinus alpinus)

Sustainability issues arise when using fish oil and vegetable oils in fish feed production for aquaculture purposes. Microbial production of single cell oil is a potential alternative as a lipid ingredient in the production of fish feed. In this study, we replaced the vegetable oils with the oleaginous yeast R. toruloides biomass in the diet of Arctic char (S. alpinus) and investigated the effects on health and composition. Measurement of fish growth parameters showed a higher liver weight and hepatosomatic index in the experimental group of fish fed partly with yeast biomass compared to a control group fed a diet with vegetable oils. No significant differences in the lipid content of muscle and liver tissues were found. The fatty acid profiles in the muscle of both fish groups were similar while the experimental fish group had a higher amount of monounsaturated fatty acids in the liver. Histology of livers showed no significant difference in the number of lipid droplets. The size of hepatic lipid droplets seemed to be related to liver fat content. Quantification of metabolites in the liver revealed no differences between the fish groups while plasma metabolites involved in energy pathways such as alanine, 3-hydroxybutyrate, creatinine, serine, betaine, and choline were significantly higher in the experimental fish group

Identification of prediagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry-based metabolomics: A case-control study nested in the Northern Sweden Health and Disease Study

Prostate cancer (PCa) is the most common cancer form in males in many European and American countries, but there are still open questions regarding its etiology. Untargeted metabolomics can produce an unbiased global metabolic profile, with the opportunity for uncovering new plasma metabolites prospectively associated with risk of PCa, providing insights into disease etiology. We conducted a prospective untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis using prediagnostic fasting plasma samples from 752 PCa case-control pairs nested within the Northern Sweden Health and Disease Study (NSHDS). The pairs were matched by age, BMI, and sample storage time. Discriminating features were identified by a combination of orthogonal projection to latent structures-effect projections (OPLS-EP) and Wilcoxon signed-rank tests. Their prospective associations with PCa risk were investigated by conditional logistic regression. Subgroup analyses based on stratification by disease aggressiveness and baseline age were also conducted. Various free fatty acids and phospholipids were positively associated with overall risk of PCa and in various stratification subgroups. Aromatic amino acids were positively associated with overall risk of PCa. Uric acid was positively, and glucose negatively, associated with risk of PCa in the older subgroup. This is the largest untargeted LC-MS based metabolomics study to date on plasma metabolites prospectively associated with risk of developing PCa. Different subgroups of disease aggressiveness and baseline age showed different associations with metabolites. The findings suggest that shifts in plasma concentrations of metabolites in lipid, aromatic amino acid, and glucose metabolism are associated with risk of developing PCa during the following two decades

Fecal Short-Chain Fatty Acid Ratios as Related to Gastrointestinal and Depressive Symptoms in Young Adults

Objective: Short-chain fatty acids (SCFAs) are produced by the gut microbiota and may reflect health. Gut symptoms are common in individuals with depressive disorders, and recent data indicate relationships between gut microbiota and psychiatric health. We aimed to investigate potential associations between SCFAs and self-reported depressive and gut symptoms in young adults.Methods: Fecal samples from 164 individuals (125 were patients with psychiatric disorders: mean [standard deviation] age = 21.9 [2.6] years, 14% men; 39 nonpsychiatric controls: age = 28.5 [9.5] years, 38% men) were analyzed for the SCFA acetate, butyrate, and propionate by nuclear magnetic resonance spectroscopy. We then compared SCFA ratios with dimensional measures of self-reported depressive and gut symptoms.Results: Depressive symptoms showed a positive association with acetate levels (rho = 0.235, p =.003) and negative associations with both butyrate (rho = -0.195, p =.014) and propionate levels (rho = -0.201, p =.009) in relation to total SCFA levels. Furthermore, symptoms of diarrhea showed positive associations with acetate (rho = 0.217, p =.010) and negative associations with propionate in relation to total SCFA levels (rho = 0.229, p = 0-007). Cluster analysis revealed a heterogeneous pattern where shifts in SCFA ratios were observed in individuals with elevated levels of depressive symptoms, elevated levels of gut symptoms, or both.Conclusions: Shifts in SCFAs are associated with both depressive symptoms and gut symptoms in young adults and may have of relevance for treatment

Oleaginous yeast Rhodotorula toruloides biomass effect on the metabolism of Arctic char (Salvelinus alpinus)

Sustainability issues arise when using fish oil and vegetable oils in fish feed production for aquaculture purposes. Microbial production of single cell oil is a potential alternative as a lipid ingredient in the production of fish feed. In this study, we replaced the vegetable oils with the oleaginous yeast R. toruloides biomass in the diet of Arctic char (S. alpinus) and investigated the effects on health and composition. Measurement of fish growth parameters showed a higher liver weight and hepatosomatic index in the experimental group of fish fed partly with yeast biomass compared to a control group fed a diet with vegetable oils. No significant differences in the lipid content of muscle and liver tissues were found. The fatty acid profiles in the muscle of both fish groups were similar while the experimental fish group had a higher amount of monounsaturated fatty acids in the liver. Histology of livers showed no significant difference in the number of lipid droplets. The size of hepatic lipid droplets seemed to be related to liver fat content. Quantification of metabolites in the liver revealed no differences between the fish groups while plasma metabolites involved in energy pathways such as alanine, 3-hydroxybutyrate, creatinine, serine, betaine, and choline were significantly higher in the experimental fish group

STAT3 regulated ARF expression suppresses prostate cancer metastasis.

Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten-deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19(ARF) as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF-Mdm2-p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14(ARF) expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition.Lukas Kenner and Jan Pencik are supported by FWF, P26011 and the Genome Research-Austria project “Inflammobiota” grants. Helmut Dolznig is supported by the Herzfelder Family Foundation and the Niederösterr. Forschungs-und Bildungsges.m.b.H (nfb). Richard Moriggl is supported by grant SFB-F2807 and SFB-F4707 from the Austrian Science Fund (FWF), Ali Moazzami is supported by Infrastructure for biosciences-Strategic fund, SciLifeLab and Formas, Zoran Culig is supported by FWF, P24428, Athena Chalaris and Stefan Rose-John are supported by the Deutsche Forschungsgemeinschaft (Grant SFB 877, Project A1and the Cluster of Excellence --“Inflammation at Interfaces”). Work of the Aberger lab was supported by the Austrian Science Fund FWF (Projects P25629 and W1213), the European FP7 Marie-Curie Initial Training Network HEALING and the priority program Biosciences and Health of the Paris-Lodron University of Salzburg. Valeria Poli is supported by the Italian Association for Cancer Research (AIRC, No IG13009). Richard Kennedy and Steven Walker are supported by the McClay Foundation and the Movember Centre of Excellence (PC-UK and Movember). Gerda Egger is supported by FWF, P27616. Tim Malcolm and Suzanne Turner are supported by Leukaemia and Lymphoma Research.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms873