PubMed

Related Articles [Impact of trauma integration treatment system on the mortality of patients with severe trauma]. Zhonghua Shao Shang Za Zhi. 2016 Jan;32(1):46-50 Authors: Sun MW, Li SJ, Jiang H, Wang ZH, Feng JZ, Yang H, Cai B, Zeng J Abstract OBJECTIVE: To quantitatively evaluate the treatment quality of trauma integration treatment system in the patients with severe trauma. METHODS: Records of patients with severe trauma hospitalized in our department from January 2010 to December 2012 were extracted from trauma database and analyzed, including gender, age, basic situation after admission [including systolic pressure, diastolic pressure, axillary temperature, heart rate, Injury Severity Score (ISS), Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score, Glasgow Coma Score, and urine volume on the first day], the first time determination values of physiological and biochemical indexes after admission (including pH value, base excess, PaCO2, PaO2, standard bicarbonate ion, leucocyte count, neutrophile granulocyte, hemoglobin, platelet count, albumin, urea nitrogen, lactic acid, blood glucose, and blood sodium), surgical situation, length of ICU stay, occurrence of major complications [including infection, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS)/multiple organ failure (MOF)], and death. Single factor analysis was used to screen death-associated exposure factors, then the exposure factors were brought into multivariate Logistic regression to establish adjustment mortality models to calculate observation/expectation (O/E) ratio of adjustment mortality of patients in these three years, and Poisson distribution was used to calculate the 95% confidence interval (CI) of O/E ratio. Data were processed with Student t test, Wilcox test, chi-square test and or Fisher's exact test. RESULTS: A total of 536 patients with severe trauma were enrolled in these three years, with 438 male (81.72%) and 98 female (18.28%). There were no statistically significant differences in gender, age, and basic situation of patients after admission among these three years (χ(2)=0.16, with t values from 0.05 to 104.50, W values from 0.008 to 104.500, P values above 0.05). There were no statistically significant differences in the first time determination values of physiological and biochemical indexes after admission including pH value, base excess, PaCO2, PaO2, hemoglobin, platelet count, and blood sodium of patients among these three years (with t values from 0.80 to 29.10, W values respectively 0.110 and 5.450, P values above 0.05), while there were statistically significant differences in standard bicarbonate ion, leucocyte count, neutrophile granulocyte, albumin, urea nitrogen, lactic acid, and blood glucose of patients among these three years (with t values from 1 542.00 to 500 000.00, W values from 637.000 to 500 000.000, P<0.05 or P<0.01). There were no statistically significant differences in surgical situation, length of ICU stay, and occurrence of major complications including infection, ARDS, and MODS/MOF in patients among these three years (with χ(2) values from 0.48 to 2.43, W =2.100, P values above 0.05). The mortality of patients in 2010, 2011, and 2012 were 11.9% (19/159), 11.2% (21/187), and 7.4% (14/190), respectively, showing a trend of decline, but there was no statistically significant difference (χ(2)=2.43, P>0.05). Death-associated exposure factors were age, ISS, APACHE Ⅱ score, urea volume on the first day, platelet count, albumin, and blood sodium. The O/E ratio of adjustment mortality (95%CI) in 2010, 2011, and 2012 were 0.727 (0.460-1.180), 0.718 (0.460-1.230), and 0.460 (0.270-0.840), respectively, showing a trend of decline each year. CONCLUSIONS: The trauma integration treatment system can improve the treatment quality of patients with severe trauma. PMID: 27426070 [PubMed - in process]

Related Articles Metabolic profile modifications in milk after enrofloxacin administration studied by liquid chromatography coupled with high resolution mass spectrometry. J Chromatogr A. 2016 Jul 7; Authors: Junza A, Saurina J, Barrón D, Minguillón C Abstract High resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was used in the search and identification of metabolites in raw milk from cows medicated with enrofloxacin. Data consisting of m/z features were taken throughout the entire chromatogram of milk samples from medicated animals and were compared with blank samples. Twenty six different compounds were identified. Some of them were attributed to structures related to enrofloxacin while others were dipeptides or tripeptides. Additionally, enrofloxacin was administered in a controlled treatment for three days. Milk was collected daily from the first day of treatment and until four days after in the search for the identified compounds. The obtained data were chemometrically treated by Principal Component Analysis. Samples were classified by this method into three different groups corresponding to days 1-2, day 3 and days 4-7 considering the different concentration profile evolution of metabolites during the days studied. Tentative metabolic pathways were designed to rationalize the presence of the newly identified compounds. PMID: 27425761 [PubMed - as supplied by publisher]

Rational and design of an overfeeding protocol in constitutional thinness: Understanding the physiology, metabolism and genetic background of resistance to weight gain. Ann Endocrinol (Paris). 2016 Jul 13; Authors: Ling Y, Galusca B, Hager J, Feasson L, Valsesia A, Epelbaum J, Alexandre V, Wynn E, Dinet C, Palaghiu R, Peoc'h M, Boirie Y, Montaurier C, Estour B, Germain N Abstract BACKGROUND: Constitutional thinness (CT) is a natural state of underweight (13-17.5kg/m(2)) without the presence of any eating disorders and abnormal hormonal profile, and with preserved menses in women. We previously conducted a four-week fat overfeeding study showing weight gain resistance in CT women and one of our main results was the identification of an energy gap: a positive energy balance (higher energy intake than energy expenditure). OBJECTIVE: This new overfeeding study is designed to confirm the energy gap and propose mechanistic hypothesis. DESIGN: A 2-week overfeeding (daily consumption of one bottle of Renutryl(®) Booster (600kcal, 30g protein, 72g carbohydrate, 21g fat) on top of the dietary intake) is performed to compare 15 women and men in each CT group (Body Mass Index [BMI]<18.5kg/m(2)) to their controls (BMI 20-25kg/m(2)). Bodyweight, food intake, energy expenditure (canopy, calorimetric chamber and Actiheart), body composition (DXA), appetite regulatory hormone profiles after a test meal, proteomics, metabolomics, urinary metabolic profiles, stool microbiome and lipids, fat and muscle transcriptomics are monitored before and after overfeeding. RESULTS AND CONCLUSIONS: Data inter-linking will be able to be established with results of this study. The findings could possibly open to therapeutic approaches to help CT patients to gain weight as well as provide a better understanding of energy regulation with regard to treat obesity (resistance to weight loss), a mirror image of CT (resistance to weight gain). PMID: 27424229 [PubMed - as supplied by publisher]

Lactation is associated with altered metabolomic signatures in women with gestational diabetes. Diabetologia. 2016 Jul 16; Authors: Much D, Beyerlein A, Kindt A, Krumsiek J, Stückler F, Rossbauer M, Hofelich A, Wiesenäcker D, Hivner S, Herbst M, Römisch-Margl W, Prehn C, Adamski J, Kastenmüller G, Theis F, Ziegler AG, Hummel S Abstract AIMS/HYPOTHESIS: Lactation for >3 months in women with gestational diabetes is associated with a reduced risk of type 2 diabetes that persists for up to 15 years postpartum. However, the underlying mechanisms are unknown. We examined whether in women with gestational diabetes lactation for >3 months is associated with altered metabolomic signatures postpartum. METHODS: We enrolled 197 women with gestational diabetes at a median of 3.6 years (interquartile range 0.7-6.5 years) after delivery. Targeted metabolomics profiles (including 156 metabolites) were obtained during a glucose challenge test. Comparisons of metabolite concentrations and ratios between women who lactated for >3 months and women who lactated for ≤3 months or not at all were performed using linear regression with adjustment for age and BMI at the postpartum visit, time since delivery, and maternal education level, and correction for multiple testing. Gaussian graphical modelling was used to generate metabolite networks. RESULTS: Lactation for >3 months was associated with a higher total lysophosphatidylcholine/total phosphatidylcholine ratio; in women with short-term follow-up, it was also associated with lower leucine concentrations and a lower total branched-chain amino acid concentration. Gaussian graphical modelling identified subgroups of closely linked metabolites within phosphatidylcholines and branched-chain amino acids that were affected by lactation for >3 months and have been linked to the pathophysiology of type 2 diabetes in previous studies. CONCLUSIONS/INTERPRETATION: Lactation for >3 months in women with gestational diabetes is associated with changes in the metabolomics profile that have been linked to the early pathogenesis of type 2 diabetes. PMID: 27423999 [PubMed - as supplied by publisher]

Sample preparation optimization in fecal metabolic profiling. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jun 28; Authors: Deda O, Chatziioannou AC, Fasoula S, Palachanis D, Raikos Ν, Theodoridis GA, Gika HG Abstract Metabolomic analysis of feces can provide useful insight on the metabolic status, the health/disease state of the human/animal and the symbiosis with the gut microbiome. As a result, recently there is increased interest on the application of holistic analysis of feces for biomarker discovery. For metabolomics applications, the sample preparation process used prior to the analysis of fecal samples is of high importance, as it greatly affects the obtained metabolic profile, especially since feces, as matrix are diversifying in their physicochemical characteristics and molecular content. However there is still little information in the literature and lack of a universal approach on sample treatment for fecal metabolic profiling. The scope of the present work was to study the conditions for sample preparation of rat feces with the ultimate goal of the acquisition of comprehensive metabolic profiles either untargeted by NMR spectroscopy and GC-MS or targeted by HILIC-MS/MS. A fecal sample pooled from male and female Wistar rats was extracted under various conditions by modifying the pH value, the nature of the organic solvent and the sample weight to solvent volume ratio. It was found that the 1/2 (wf/vs) ratio provided the highest number of metabolites under neutral and basic conditions in both untargeted profiling techniques. Concerning LC-MS profiles, neutral acetonitrile and propanol provided higher signals and wide metabolite coverage, though extraction efficiency is metabolite dependent. PMID: 27423778 [PubMed - as supplied by publisher]

Metabolomic-based biomarker discovery for non-invasive lung cancer screening: A case study. Biochim Biophys Acta. 2016 Jul 14; Authors: O'Shea K, Cameron SJ, Lewis KE, Lu C, Mur LA Abstract BACKGROUND: Lung cancer (LC) is one of the leading lethal cancers worldwide, with an estimated 18.4% of all cancer deaths being attributed to the disease. Despite developments in cancer diagnosis and treatment over the previous thirty years, LC has seen little to no improvement in the overall five year survival rate after initial diagnosis. METHODS: In this paper, we extended a recent study which profiled the metabolites in sputum from patients with lung cancer and age-matched volunteers smoking controls using flow infusion electrospray ion mass spectrometry. We selected key metabolites for distinguishing between different classes of lung cancer, and employed artificial neural networks and leave-one-out cross-validation to evaluate the predictive power of the identified biomarkers. RESULTS: The neural network model showed excellent performance in classification between lung cancer and control groups with the area under the receiver operating characteristic curve of 0.99. The sensitivity and specificity of for detecting cancer from controls were 96% and 94% respectively. Furthermore, we have identified six putative metabolites that were able to discriminate between sputum samples derived from patients suffering small cell lung cancer (SCLC) and non-small cell lung cancer. These metabolites achieved excellent cross validation performance with a sensitivity of 80% and specificity of 100% for predicting SCLC. CONCLUSIONS: These results indicate that sputum metabolic profiling may have potential for screening of lung cancer and lung cancer recurrence, and may greatly improve effectiveness of clinical intervention. PMID: 27423423 [PubMed - as supplied by publisher]

Metabolomic approach for identifying and visualizing molecular tissue markers in tadpoles of Xenopus tropicalis by mass spectrometry imaging. Biol Open. 2016 Jul 15; Authors: Goto-Inoue N, Kashiwagi A, Kashiwagi K, Mori T Abstract In developmental and cell biology it is crucial to evaluate the dynamic profiles of metabolites. An emerging frog model system using Xenopus tropicalis, whose genome sequence and inbred strains are available, is now ready for metabolomics investigation in amphibians. In this study we applied matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) analyses to identify and visualize metabolomic molecular markers in tadpoles of Xenopus tropicalisWe detected tissue-specific peaks and visualized their distribution in tissues. We distinguished 19 tissues and their specific peaks. We identified, for the first time, some of their molecular localizations via tandem mass spectrometric analysis: hydrocortisone in artery, L-DOPA in rhombencephalon, taurine in eye, corticosterone in gill, heme in heart, inosine monophosphate and carnosine in muscle, dopamine in nerves, and phosphatidylethanolamine (16:0/20:4) in pharynx.This is the first MALDI-MSI study of X. tropicalis tadpoles. In small tadpoles it is hard to distinguish and dissect the various organs. Furthermore, until now we have no data about the metabolomic profile of each organ. Our results suggest that MALDI-MSI is potentially a powerful tool for examining the dynamics of metabolomics in metamorphosis as well as conformational changes due to metabolic changes. PMID: 27422901 [PubMed - as supplied by publisher]

Impact of Cranberries on Gut Microbiota and Cardiometabolic Health: Proceedings of the Cranberry Health Research Conference 2015. Adv Nutr. 2016 Jul;7(4):759S-70S Authors: Blumberg JB, Basu A, Krueger CG, Lila MA, Neto CC, Novotny JA, Reed JD, Rodriguez-Mateos A, Toner CD Abstract Recent advances in cranberry research have expanded the evidence for the role of this Vaccinium berry fruit in modulating gut microbiota function and cardiometabolic risk factors. The A-type structure of cranberry proanthocyanidins seems to be responsible for much of this fruit's efficacy as a natural antimicrobial. Cranberry proanthocyanidins interfere with colonization of the gut by extraintestinal pathogenic Escherichia coli in vitro and attenuate gut barrier dysfunction caused by dietary insults in vivo. Furthermore, new studies indicate synergy between these proanthocyanidins, other cranberry components such as isoprenoids and xyloglucans, and gut microbiota. Together, cranberry constituents and their bioactive catabolites have been found to contribute to mechanisms affecting bacterial adhesion, coaggregation, and biofilm formation that may underlie potential clinical benefits on gastrointestinal and urinary tract infections, as well as on systemic anti-inflammatory actions mediated via the gut microbiome. A limited but growing body of evidence from randomized clinical trials reveals favorable effects of cranberry consumption on measures of cardiometabolic health, including serum lipid profiles, blood pressure, endothelial function, glucoregulation, and a variety of biomarkers of inflammation and oxidative stress. These results warrant further research, particularly studies dedicated to the elucidation of dose-response relations, pharmacokinetic/metabolomics profiles, and relevant biomarkers of action with the use of fully characterized cranberry products. Freeze-dried whole cranberry powder and a matched placebo were recently made available to investigators to facilitate such work, including interlaboratory comparability. PMID: 27422512 [PubMed - in process]

Comparative proteomic and metabolomic analysis reveal the antiosteoporotic molecular mechanism of icariin from Epimedium brevicornu Maxim. J Ethnopharmacol. 2016 Jul 12; Authors: Xue L, Jiang Y, Han T, Zhang N, Qin L, Xin H, Zhang Q Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Icariin, a principal flavonoid glycoside of Epimedium brevicornu Maxim, has been widely proved to possess antiosteoporotic activity with promoting bone frormation and decreasing bone resorption. However, the involving mechanisms remain unclear. AIM OF THE STUDY: To clear a global insight of signal pathways involved in anti-osteoporotic mechanism of icariin at proteins and metabolites level by integrating the proteomics and NMR metabonomics, in a systems biology approach. MATERIAL AND METHODS: Mice were divided into sham, OVX model and icariin-treated OVX group, after 90 days treatment, difference gel electrophoresis combined with MALDI-TOF/TOF proteomics analysis on bone femur and serum metabolomics were carried out for monitor intracellular processes and elucidate anti-osteoporotic mechanism of icariin. Osteoblast and osteoclast were applied to evaluate the potential signal pathways. RESULTS: 23 proteins in bone femur, and 8 metabolites in serum, were significantly altered and identified, involving in bone remodeling, energy metabolism, cytoskeleton, lipid metabolism, MAPK signaling, Ca(2+) signaling et, al. Furthermore, animal experiment show icariin could enhance the BMD and BMC, decrease CTX-I level in ovariectomized mice. The mitochondrial membrane potential and the intracellular ATP levels were increased significantly, and the cytoskeleton were improved in icariin-treatment osteoblast and osteoclast. Icariin also increased mRNA expression of Runx2 and osterix of OB, decreased CTR and CAII mRNA expression and protein expression of P38 and JNK. However, icariin did not reveal any inhibition of the collagenolytic activity of cathepsin K, mRNA expression of MMP-9 and protein expression of ERK in osteoclast. CONCLUSION: we consider icariin as multi-targeting compounds for treating with osteoporosis, involve intiating osteoblastogenesis, inhibiting adipogenesis, and preventing osteoclast differentiation. PMID: 27422162 [PubMed - as supplied by publisher]

Perinatal Triphenyl Phosphate Exposure Accelerates Type 2 Diabetes Onset and Increases Adipose Accumulation in UCD-Type 2 Diabetes Mellitus Rats. Reprod Toxicol. 2016 Jul 12; Authors: Green AJ, Graham JL, Gonzalez EA, La Frano MR, Petropoulou SE, Park JS, Newman JW, Stanhope KL, Havel PJ, La Merrill MA Abstract Triphenyl phosphate (TPhP) is a flame retardant additive frequently found in consumer products and household dust. We administered 170μg of TPhP in maternal food from gestational day 8.5 to weaning and evaluated metabolic phenotypes of 3.5 month old male and female rats, and weight-matched males up to 6 months, to assess the development of obesity and type 2 diabetes mellitus (T2DM), respectively. Perinatal TPhP exposure increased body and fat mass in 3.5 month old male and female rats, while leptin and cumulative energy intake were elevated in males and females, respectively. Independent of body mass, perinatal TPhP exposure accelerated T2DM onset in males and increased plasma non-esterified- fasting fatty acids. These observations suggest that perinatal exposure to TPhP exacerbates the development of obesity in male and female UCDavis-T2DM rats and accelerates T2DM onset in male UCD-T2DM rats. PMID: 27421578 [PubMed - as supplied by publisher]

The Karlsruhe Metabolomics and Nutrition (KarMeN) Study: Protocol and Methods of a Cross-Sectional Study to Characterize the Metabolome of Healthy Men and Women. JMIR Res Protoc. 2016;5(3):e146 Authors: Bub A, Kriebel A, Dörr C, Bandt S, Rist M, Roth A, Hummel E, Kulling S, Hoffmann I, Watzl B Abstract BACKGROUND: The human metabolome is influenced by various intrinsic and extrinsic factors. A precondition to identify such biomarkers is the comprehensive understanding of the composition and variability of the metabolome of healthy humans. Sample handling aspects have an important impact on the composition of the metabolome; therefore, it is crucial for any metabolomics study to standardize protocols on sample collection, preanalytical sample handling, storage, and analytics to keep the nonbiological variability as low as possible. OBJECTIVE: The main objective of the KarMeN study is to analyze the human metabolome in blood and urine by targeted and untargeted metabolite profiling (gas chromatography-mass spectrometry [GC-MS], GC×GC-MS, liquid chromatography-mass spectrometry [LC-MS/MS], and(1)H nuclear magnetic resonance [NMR] spectroscopy) and to determine the impact of sex, age, body composition, diet, and physical activity on metabolite profiles of healthy women and men. Here, we report the outline of the study protocol with special regard to all aspects that should be considered in studies applying metabolomics. METHODS: Healthy men and women, aged 18 years or older, were recruited. In addition to a number of anthropometric (height, weight, body mass index, waist circumference, body composition), clinical (blood pressure, electrocardiogram, blood and urine clinical chemistry) and functional parameters (lung function, arterial stiffness), resting metabolic rate, physical activity, fitness, and dietary intake were assessed, and 24-hour urine, fasting spot urine, and plasma samples were collected. Standard operating procedures were established for all steps of the study design. Using different analytical techniques (LC-MS, GC×GC-MS,(1)H NMR spectroscopy), metabolite profiles of urine and plasma were determined. Data will be analyzed using univariate and multivariate as well as predictive modeling methods. RESULTS: The project was funded in 2011 and enrollment was carried out between March 2012 and July 2013. A total of 301 volunteers were eligible to participate in the study. Metabolite profiling of plasma and urine samples has been completed and data analysis is currently underway. CONCLUSIONS: We established the KarMeN study applying a broad set of clinical and physiological examinations with a high degree of standardization. Our experimental approach of combining scheduled timing of examinations and sampling with the multiplatform approach (GC×GC-MS, GC-MS, LC-MS/MS, and(1)H NMR spectroscopy) will enable us to differentiate between current and long-term effects of diet and physical activity on metabolite profiles, while enabling us at the same time to consider confounders such as age and sex in the KarMeN study. TRIAL REGISTRATION: German Clinical Trials Register DRKS00004890; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00004890 (Archived by WebCite at http://www.webcitation.org/6iyM8dMtx). PMID: 27421387 [PubMed]

Hydrogen rearrangement rules: computational MS/MS fragmentation and structure elucidation using MS-FINDER software. Anal Chem. 2016 Jul 15; Authors: Tsugawa H, Kind T, Nakabayashi R, Yukihira D, Tanaka W, Cajka T, Saito K, Fiehn O, Arita M Abstract Compound identification from accurate mass MS/MS spectra is a bottleneck for untargeted metabolomics. In this study, we propose nine rules of hydrogen rearrangement (HR) during bond cleavages in low-energy collision-induced dissociation (CID). These rules are based on the classic even-electron rule and cover heteroatoms and multi-stage fragmentation. We evaluated our HR rules by the statistics of MassBank MS/MS spectra in addition to enthalpy calculations, yielding three levels of computational MS/MS annotation: 'resolved' (regular HR behavior following HR rules), 'semi-resolved' (irregular HR behavior), and 'formula-assigned' (lacking structure assignment). With this nomenclature, 78.4% of total 18,506 MS/MS fragment ions in the MassBank database and 84.8% of total 36,370 MS/MS fragment ions in the GNPS database were (semi-) resolved by predicted bond cleavages. We also introduce the MS-FINDER software for structure elucidation. Molecular formulas of precursor ions are determined from accurate mass, isotope ratio, and product ion information. All isomer structures of the predicted formula are retrieved from metabolome databases and MS/MS fragmentations are predicted in silico. The structures are ranked by a combined weighting score considering bond dissociation energies, mass accuracies, fragment linkages and, most importantly, nine HR rules. The program was validated by its ability to correctly calculate molecular formulas with 98.0% accuracy for 5,063 MassBank MS/MS records, and to yield the correct structural isomer with 82.1% accuracy within the top-3 candidates. In a test with 936 manually identified spectra from an untargeted HILIC-QTOF MS data set of human plasma, formulas were correctly predicted in 90.4% of the cases, and the correct isomer structure was retrieved at 80.4% probability within the top-3 candidates, including for compounds that were absent in mass spectral libraries. The MS-FINDER software is freely available at http://prime.psc.riken.jp/. PMID: 27419259 [PubMed - as supplied by publisher]

A 3-methylcrotonyl-CoA carboxylase deficient human skin fibroblast transcriptome reveals underlying mitochondrial dysfunction and oxidative stress. Int J Biochem Cell Biol. 2016 Jul 11; Authors: Zandberg L, van Dyk HC, van der Westhuizen FH, van Dijk AA Abstract Isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive inherited metabolic disease of leucine catabolism with a highly variable phenotype. Apart from extensive mutation analyses of the MCCC1 and MCCC2 genes encoding 3-methylcrotonyl-CoA carboxylase (EC 6.4.1.4), molecular data on MCC deficiency gene expression studies in human tissues is lacking. For IEMs, unbiased '-omics' approaches are starting to reveal the secondary cellular responses to defects in biochemical pathways. Here we present the first whole genome expression profile of immortalized cultured skin fibroblast cells of two clinically affected MCC deficient patients and two healthy individuals generated using Affymetrix(®)HuExST1.0 arrays. There were 16191 significantly differentially expressed transcript IDs of which 3591 were well annotated and present in the predefined knowledge database of Ingenuity Pathway Analysis software used for downstream functional analyses. The most noticeable feature of this MCCA deficient skin fibroblast transcriptome was the typical genetic hallmark of mitochondrial dysfunction, decreased antioxidant response and disruption of energy homeostasis, which was confirmed by mitochondrial functional analyses. The MCC deficient transcriptome seems to predict oxidative stress that could alter the complex secondary cellular response that involve genes of the glycolysis, the TCA cycle, OXPHOS, gluconeogenesis, β-oxidation and the branched-chain fatty acid metabolism. An important emerging insight from this human MCCA transcriptome in combination with previous reports is that chronic exposure to the primary and secondary metabolites of MCC deficiency and the resulting oxidative stress might impact adversely on the quality of life and energy levels, irrespective of whether MCC deficient individuals are clinically affected or asymptomatic. PMID: 27417235 [PubMed - as supplied by publisher]

32nd International Symposium on Microscale Separations and Bioanalysis (MSB 2016). Bioanalysis. 2016 Jul 15; Authors: Ramautar R Abstract 32nd International Symposium on Microscale Separations and Bioanalysis, Niagara-on-the-Lake, Canada, 3-7 April 2016 The 32nd edition of the International Symposium on Microscale Separations and Bioanalysis (MSB) was held in Niagara-on-the-Lake, Canada, from 3 to 7 April 2016. This article outlines the aim and the main distinctive features of the MSB symposium. A selection of the scientific research presented at MSB 2016 is highlighted with a special focus on microscale separation developments in the fields of sample preparation, (glyco)proteomics and metabolomics. PMID: 27416852 [PubMed - as supplied by publisher]

Metabonomics applied in exploring the antitumour mechanism of physapubenolide on hepatocellular carcinoma cells by targeting glycolysis through the Akt-p53 pathway. Sci Rep. 2016;6:29926 Authors: Ma T, Fan BY, Zhang C, Zhao HJ, Han C, Gao CY, Luo JG, Kong LY Abstract Metabolomics can be used to identify potential markers and discover new targets for future therapeutic interventions. Here, we developed a novel application of the metabonomics method based on gas chromatography-mass spectrometry (GC/MS) analysis and principal component analysis (PCA) for rapidly exploring the anticancer mechanism of physapubenolide (PB), a cytotoxic withanolide isolated from Physalis species. PB inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vivo, accompanied by apoptosis-related biochemical events, including the cleavage of caspase-3/7/9 and PARP. Metabolic profiling analysis revealed that PB disturbed the metabolic pattern and significantly decreased lactate production. This suggests that the suppression of glycolysis plays an important role in the anti-tumour effects induced by PB, which is further supported by the decreased expression of glycolysis-related genes and proteins. Furthermore, the increased level of p53 and decreased expression of p-Akt were observed, and the attenuated glycolysis and enhanced apoptosis were reversed in the presence of Akt cDNA or p53 siRNA. These results confirm that PB exhibits anti-cancer activities through the Akt-p53 pathway. Our study not only reports for the first time the anti-tumour mechanism of PB, but also suggests that PB is a promising therapeutic agent for use in cancer treatments and that metabolomic approaches provide a new strategy to effectively explore the molecular mechanisms of promising anticancer compounds. PMID: 27416811 [PubMed - in process]

Genetic markers: Potential candidates for cardiovascular disease. Int J Cardiol. 2016 Jun 27;220:914-923 Authors: Rather RA, Dhawan V Abstract The effective prevention of cardiovascular disease depends upon the ability to recognize the high-risk individuals at an early stage of the disease or long before the development of adverse events. Evolving technologies in the fields of proteomics, metabolomics, and genomics have played a significant role in the discovery of cardiovascular biomarkers, but so far these methods have achieved the modest success. Hence, there is a crucial need for more reliable, suitable, and lasting diagnostic and therapeutic markers to screen the disease well in time to start the clinical aid to the patients. Gene polymorphisms associated with the cardiovascular disease play a decisive role in the disease onset. Therefore, the genetic marker evaluation to classify high-risk patients from low-risk patients trends an effective approach to patient management and care. Currently, there are no genetic markers available for extensive adoption as risk factors for coronary vascular disease, yet, there are numerous promising, biologically acceptable candidates. Many of these gene biomarkers, alone or in combination, can play an essential role in the prediction of cardiovascular risk. The present review highlights some putative emerging genetic biomarkers that could facilitate more authentic and fast diagnosis of CVD. This review also briefly describes few technological approaches employed in the biomarker search. PMID: 27416153 [PubMed - as supplied by publisher]

Emerging Biomarkers for the Diagnosis and Monitoring of Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2016 Jul 12; Authors: Soubières AA, Poullis A Abstract There is currently no single test available to confidently diagnose cases of inflammatory bowel disease (IBD). Physicians rely on a number of diagnostic tools, including clinical evaluation, serum testing, and imaging, which are used on conjunction with endoscopic evaluation. It is often difficult to determine whether patients with abdominal pain and change in bowel habit have functional bowel symptoms or whether they have a true diagnosis of IBD. Even once a diagnosis of IBD has been made, a significant proportion of patients are labeled with the term "indeterminate colitis" where histological sampling cannot confidently subclassify patients as either Crohn's or ulcerative colitis. Colonoscopy is an inconvenient and uncomfortable test for most patients. In addition, it is not without serious risks of perforation, as well as risks which can be associated with sedation and analgesia given during the procedure. The use of biomarkers to aid in the diagnosis, subclassification, and monitoring of IBD is an ever expanding area. In this review, we have concentrated on noninvasive biomarkers of IBD, because these are more acceptable to patients and easier to perform in everyday clinical practice. We will first touch on those biomarkers currently well established and in wide clinical use, such as C-reactive protein, ESR. Faecal calprotectin and their use in the diagnosis of IBD. Following on, we will review more novel biomarkers and their use in subclassification and monitoring of IBD, including a variety of antibodies, genetics, and microRNAs, as well as touching on metabolomics. PMID: 27416044 [PubMed - as supplied by publisher]

Ten Simple Rules for Taking Advantage of Git and GitHub. PLoS Comput Biol. 2016 Jul;12(7):e1004947 Authors: Perez-Riverol Y, Gatto L, Wang R, Sachsenberg T, Uszkoreit J, Leprevost FD, Fufezan C, Ternent T, Eglen SJ, Katz DS, Pollard TJ, Konovalov A, Flight RM, Blin K, Vizcaíno JA PMID: 27415786 [PubMed - as supplied by publisher]

Seeking an objective diagnosis of depression. Biomark Med. 2016 Jul 14; Authors: Bilello JA Abstract Major depressive disorder (MDD: unipolar depression) is widely distributed in the USA and world-wide populations and it is one of the leading causes of disability in both adolescents and adults. Traditional diagnostic approaches for MDD are based on patient interviews, which provide a subjective assessment of clinical symptoms which are frequently shared with other maladies. Reliance upon clinical assessments and patient interviews for diagnosing MDD is frequently associated with misdiagnosis and suboptimal treatment outcomes. As such, there is increasing interest in the identification of objective methods for the diagnosis of depression. Newer technologies from genomics, transcriptomics, proteomics, metabolomics and imaging are technically sophisticated and objective but their application to diagnostic tests in psychiatry is still emerging. This brief overview evaluates the technical basis for these technologies and discusses how the extension of their clinical performance can lead to an objective diagnosis of MDD. PMID: 27415130 [PubMed - as supplied by publisher]

Ultrafast Online SPE-MS/MS Method for Quantification of 3 Tyrosine Kinase Inhibitors in Human Plasma. Ther Drug Monit. 2016 Aug;38(4):516-524 Authors: Vrobel I, Janečková H, Faber E, Bouchalová K, Mičová K, Friedecký D, Adam T Abstract BACKGROUND: With an increasing number of cancer patients receiving tyrosine kinase inhibitors (TKIs), therapeutic drug monitoring of these molecules is becoming more widespread today. It is mainly based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) methods with typical run times of several minutes. In an online solid phase extraction-MS/MS (SPE-MS/MS) system, the chromatography column is replaced with a reusable solid phase extraction (SPE) cartridge and the analysis time is shortened to less than half a minute. The aim of this study was to develop such a method and test the performance of this high-throughput system in the analysis of imatinib (IMA), nilotinib (NIL), and lapatinib (LAP) in human plasma. METHODS: Samples were prepared by simple protein precipitation with methanol containing deuterated internal standards. After centrifugation, the supernatant was diluted 10 fold with a mixture of methanol and water (1:1). A C4 cartridge was used for SPE and the analytes were eluted by acetonitrile. All the analytes were measured within a wide calibration range (50-5000 ng/mL for nilotinib and imatinib, 100-10,000 ng/mL for lapatinib). The method was compared with the LC-MS/MS method by the analysis of 176 clinical samples. RESULTS: Intraday and interday inaccuracies within 15% and a coefficient of variation less than 15% were achieved for all the TKIs that were measured. Even though the matrix effects were higher in comparison with LC-MS/MS methods, their effect on the performance of the method was eliminated by the usage of deuterated internal standards. The total run time of the new method was 29 seconds for one analysis and the results were fully comparable with LC-MS/MS. CONCLUSIONS: Routine clinical practice requiring high-throughput methods for therapeutic drug monitoring of TKIs may benefit from the online SPE-MS/MS method that provides fast, low-cost analysis, and results that are comparable with conventional methods. PMID: 27414975 [PubMed - as supplied by publisher]