Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 1 hour 15 min ago

Differential CO2 effect on primary carbon metabolism of flag leaves in durum wheat (Triticum durum Desf.).

Thu, 18/06/2015 - 14:51
Differential CO2 effect on primary carbon metabolism of flag leaves in durum wheat (Triticum durum Desf.). Plant Cell Environ. 2015 Jun 17; Authors: Aranjuelo I, Erice G, Sanz-Sáez A, Abadie C, Gilard F, Gil E, Avice JC, Staudinger C, Wienkoop S, Araus JL, Bourguignon J, Irigoyen JJ, Tcherkez G Abstract C sink/source balance and N assimilation have been identified as target processes conditioning crop responsiveness to elevated CO2 . However, little is known about phenology-driven modifications of C and N primary metabolism at elevated CO2 in cereals such as wheat. Here, we examined the differential effect of elevated CO2 at two development stages (onset of flowering, onset of grain filling) in durum wheat (Triticum durum, var. Sula) using physiological measurements (photosynthesis, isotopes), metabolomics, proteomics and (15) N-labelling. Our results show that growth at elevated CO2 was accompanied by photosynthetic acclimation through a lower internal (mesophyll) conductance but no significant effect on Rubisco content, maximal carboxylation or electron transfer. Growth at elevated CO2 altered photosynthate export and tended to accelerate leaf N remobilization, which was visible for several proteins and amino acids, as well as lysine degradation metabolism. However, grain biomass produced at elevated CO2 was larger and less N-rich, suggesting that nitrogen use efficiency rather than photosynthesis is an important target for improvement, even in good CO2 -responsive cultivars. PMID: 26081746 [PubMed - as supplied by publisher]

Distribution and biomarker of carbon-14 labeled fullerene C60 ([(14) C(U)]C60 ) in pregnant and lactating rats and their offspring after maternal intravenous exposure.

Thu, 18/06/2015 - 14:51
Distribution and biomarker of carbon-14 labeled fullerene C60 ([(14) C(U)]C60 ) in pregnant and lactating rats and their offspring after maternal intravenous exposure. J Appl Toxicol. 2015 Jun 17; Authors: Snyder RW, Fennell TR, Wingard CJ, Mortensen NP, Holland NA, Shannahan JH, Pathmasiri W, Lewin AH, Sumner SC Abstract A comprehensive distribution study was conducted in pregnant and lactating rats exposed to a suspension of uniformly carbon-14 labeled C60 ([(14) C(U)]C60 ). Rats were administered [(14) C(U)]C60 (~0.2 mg [(14) C(U)]C60 kg(-1) body weight) or 5% polyvinylpyrrolidone (PVP)-saline vehicle via a single tail vein injection. Pregnant rats were injected on gestation day (GD) 11 (terminated with fetuses after either 24 h or 8 days), GD15 (terminated after 24 h or 4 days), or GD18 (terminated after 24 h). Lactating rats were injected on postnatal day 8 and terminated after 24 h, 3 or 11 days. The distribution of radioactivity in pregnant dams was influenced by both the state of pregnancy and time of termination after exposure. The percentage of recovered radioactivity in pregnant and lactating rats was highest in the liver and lungs. Radioactivity was quantitated in over 20 tissues. Radioactivity was found in the placenta and in fetuses of pregnant dams, and in the milk of lactating rats and in pups. Elimination of radioactivity was < 2% in urine and feces at each time point. Radioactivity remained in blood circulation up to 11 days after [(14) C(U)]C60 exposure. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impacts of [(14) C(U)]C60 exposure. Oxidative stress was elevated in female pups of exposed dams. Metabolomics analysis of urine showed that [(14) C(U)]C60 exposure to pregnant rats impacted the pathways of vitamin B, regulation of lipid and sugar metabolism and aminoacyl-tRNA biosynthesis. This study demonstrated that [(14) C(U)]C60 crosses the placenta at all stages of pregnancy examined, and is transferred to pups via milk. Copyright © 2015 John Wiley & Sons, Ltd. PMID: 26081520 [PubMed - as supplied by publisher]

NMR based serum metabolomics discriminates Takayasu Arteritis from Healthy Individuals: A proof of principle study.

Thu, 18/06/2015 - 14:51
NMR based serum metabolomics discriminates Takayasu Arteritis from Healthy Individuals: A proof of principle study. J Proteome Res. 2015 Jun 17; Authors: Guleria A, Misra DP, Rawat A, Dubey D, Khetrapal CL, Bacon P, Misra R, Kumar D Abstract Takayasu Arteritis (TA) is a debilitating, systemic disease which involves the aorta and large arteries in a chronic inflammatory process leading to vessel stenosis. Initially, the disease remains clinically silent (or remains undetected) until the patients present with vascular occlusion. Therefore, new methods for appropriate and timely diagnosis of TA cases are needed to start proper therapy on time and also to monitor the patient's response to the given treatment. In this context, NMR-based serum metabolomic profiling has been explored in this proof of principle study for the first time to determine characteristic metabolites that could potentially be helpful for diagnosis and prognosis of TA. Serum metabolic profiling of TA patients (n = 29) and healthy controls (n = 30) was performed using 1D 1H NMR spectroscopy and possible biomarker metabolites were identified. Using projection to least squares discriminant analysis, we could distinguish TA patients from healthy controls. Compared to healthy controls, the TA patients had (a) increased serum levels of choline metabolites, LDL cholesterol, N-acetyl glycoproteins (NAGs), and glucose and (b) decreased serum levels of lactate, lipids, HDL cholesterol, glucogenic amino acids. The results of this study are preliminary and need to be confirmed in a prospective study. PMID: 26081138 [PubMed - as supplied by publisher]

Rapid and reliable identification of phospholipids for untargeted metabolomics with LC-ESI-QTOF-MS/MS.

Thu, 18/06/2015 - 14:51
Rapid and reliable identification of phospholipids for untargeted metabolomics with LC-ESI-QTOF-MS/MS. J Proteome Res. 2015 Jun 17; Authors: Godzien J, Ciborowski M, Martínez-Alcázar MP, Samczuk P, Kretowski A, Barbas C Abstract Lipids are important components of biological systems, and their role is currently investigated by application of untargeted, holistic approaches such us metabolomics/lipidomics. Acquired data is analysed to find significant signals responsible for the differentiation between investigated conditions. Subsequently identification has to be performed to bring biological meaning to the obtained results. Lipid identification seems to be relatively easy due to the known characteristic fragments, however large number of structural isomers and the formation of different adducts, makes it challenging and at risk of misidentification. The inspection of data, acquired for plasma samples by a standard metabolic fingerprinting method, revealed multi-signals formation for phosphatidylcholines, phosphatidylethanolamines and sphingomyelines by formation of ionssuch as: [M+H]+, [M+Na]+, [M+K]+ in positive ionisation mode, [M-H]-, [M+HCOO]- and [M+Cl]- in negative mode. Moreover sodium formate cluster formation was found for [M+H.HCOONa]+ and [H-H.HCOONa]-. The MS/MS spectrum obtained for each of the multi-ions revealed significant differences in the fragmentation, which were confirmed by analysis of the samples in two independent research centres. After inspection of an acquired spectra, a list of characteristic and diagnostic fragments was proposed; which allowed for easy, quick and robust lipid identification providing information about the head group, formed adduct and fatty acyl composition. This ensures successful identification which is of great importance for contextualisation of data and results validation. PMID: 26080858 [PubMed - as supplied by publisher]

[Hypothesis and application of bimolecular marking methods in Chinese materia medica].

Thu, 18/06/2015 - 14:51
[Hypothesis and application of bimolecular marking methods in Chinese materia medica]. Zhongguo Zhong Yao Za Zhi. 2015 Jan;40(2):165-8 Authors: Huang LQ, Qian D, Deng C Abstract Based on the current shortage of genuine/false authentication and quality evaluation in the molecular identification, and the weak functional gene research in the establishment of two-dimensional molecular markering methods for Chinese materia medica, the authors proposed a new method, the bimolecular marking methods (BIMM) for Chinese materia medica, combining DNA marker and metabolomics marker, that could simultaneously research the species and quality differences at the molecular level at the present stage. The authors introduced the concept, principle, methods, and technical process of BIMM, and summarized the technical advantages in this paper. Meanwhile, the application of BIMM in the identification of multiple sources of Chinese materia medica, years-identification, different locations, elite germplasm research, discovery of new drugs resources, protection of new varieties was also discussed. As a supplement of two-dimensional molecular markering method for Chinese materia medica, BIMM would not only expand connotation of identification of Chinese materia medica but also provide another effective way for quality evaluating. PMID: 26080538 [PubMed - in process]

Lipid profiling reveals different therapeutic effects of metformin and glipizide in patients with type 2 diabetes and coronary artery disease.

Thu, 18/06/2015 - 14:51
Related Articles Lipid profiling reveals different therapeutic effects of metformin and glipizide in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2014 Oct;37(10):2804-12 Authors: Zhang Y, Hu C, Hong J, Zeng J, Lai S, Lv A, Su Q, Dong Y, Zhou Z, Tang W, Zhao J, Cui L, Zou D, Wang D, Li H, Liu C, Wu G, Shen J, Zhu D, Wang W, Shen W, Ning G, Xu G Abstract OBJECTIVE: We recently demonstrated a beneficial effect of metformin compared with glipizide in type 2 diabetic patients regarding cardiovascular outcomes for 3-year treatment in the SPREAD-DIMCAD study. However, the potential mechanism for the clinical effects remains unclear. Here, we performed a comprehensive lipidomics study to evaluate the different lipid metabolites in serum samples obtained from participants in this study. RESEARCH DESIGN AND METHODS: Liquid chromatography-quadrupole time of flight-mass spectrometry was used to evaluate the different lipid metabolites in serum samples obtained from the participants (21 patients in glipizide group and 23 patients in metformin group) before and after each year of treatment (at 0 [baseline], 1, 2, and 3 years of study drug administration). RESULTS: A total of 118 serum lipid molecular species was identified and quantified. During treatment, metformin induced a substantially greater change in serum lipid species compared with glipizide, especially at the 2- and 3-year time points (with 2, 11, and 12 lipid species being significantly different between the groups after each year of treatment [1, 2, or 3 years], P < 0.05). Among the significantly changed lipid species, three lipid metabolites were linked to long-term composite cardiovascular events (adjusted P < 0.05). After treatment, triacylglycerols (TAGs) of a relatively higher carbon number showed a clearly increased trend in metformin group compared with the glipizide group, whereas the changes in TAGs with different double bonds were minimal. CONCLUSIONS: Our findings revealed the differential therapeutic effects of metformin and glipizide on comprehensive lipidomics, which were comparable with their different long-term effects on cardiovascular outcomes. PMID: 25011952 [PubMed - indexed for MEDLINE]

Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition.

Thu, 18/06/2015 - 14:51
Related Articles Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition. Oncogene. 2015 Mar 19;34(12):1475-86 Authors: Bonora M, Wieckowski MR, Chinopoulos C, Kepp O, Kroemer G, Galluzzi L, Pinton P Abstract The term mitochondrial permeability transition (MPT) is commonly used to indicate an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes. Widespread MPT has catastrophic consequences for the cell, de facto marking the boundary between cellular life and death. MPT results indeed in the structural and functional collapse of mitochondria, an event that commits cells to suicide via regulated necrosis or apoptosis. MPT has a central role in the etiology of both acute and chronic diseases characterized by the loss of post-mitotic cells. Moreover, cancer cells are often relatively insensitive to the induction of MPT, underlying their increased resistance to potentially lethal cues. Thus, intense efforts have been dedicated not only at the understanding of MPT in mechanistic terms, but also at the development of pharmacological MPT modulators. In this setting, multiple mitochondrial and extramitochondrial proteins have been suspected to critically regulate the MPT. So far, however, only peptidylprolyl isomerase F (best known as cyclophilin D) appears to constitute a key component of the so-called permeability transition pore complex (PTPC), the supramolecular entity that is believed to mediate MPT. Here, after reviewing the structural and functional features of the PTPC, we summarize recent findings suggesting that another of its core components is represented by the c subunit of mitochondrial ATP synthase. PMID: 24727893 [PubMed - indexed for MEDLINE]

Statistical-based approach in potential diagnostic application of urinary nucleosides in urogenital tract cancer.

Wed, 17/06/2015 - 14:16
Statistical-based approach in potential diagnostic application of urinary nucleosides in urogenital tract cancer. Biomark Med. 2015 Jun;9(6):577-595 Authors: Daghir-Wojtkowiak E, Struck-Lewicka W, Waszczuk-Jankowska M, Markuszewski M, Kaliszan R, Markuszewski MJ Abstract AIM: We aimed at evaluation the potential diagnostic role of urinary nucleosides in urogenital tract cancer. MATERIALS & METHODS: Concentrations of 12 nucleosides determined by LC-MS/MS were subjected to correlation, association and interaction analyses. RESULTS: We identified six pairs of nucleosides differently correlated in the group of patients and controls (p < 0.05). N-2-methylguanosine (odds ratio: 4.82; 95% CI: 1.78-12.93; p = 0.002) and N,N-dimethylguanosine (odds ratio: 5.45; 95% CI: 1.78-16.44; p = 0.003), were significantly associated with the disease risk (p-corrected = 0.004). Interaction between N-2-methylguanosine and adenosine (p-interaction = 0.019) suggested their multiplicative effect on the outcome. CONCLUSION: Urinary nucleosides, namely N,N-dimethylguanosine and N-2-methylguanosine may have the potential to serve as prognostic biomarkers. Gender-specific differences in urogenital tract cancer are likely to occur. PMID: 26079962 [PubMed - as supplied by publisher]

Molecular anatomy of ascending aorta in atherosclerosis by MS Imaging: Specific lipid and protein patterns reflect pathology.

Wed, 17/06/2015 - 14:16
Molecular anatomy of ascending aorta in atherosclerosis by MS Imaging: Specific lipid and protein patterns reflect pathology. J Proteomics. 2015 Jun 12; Authors: Martin-Lorenzo M, Balluff B, Maroto AS, Carreira RJ, van Zeijl RJ, Gonzalez-Calero L, de la Cuesta F, Barderas MG, Lopez-Almodovar LF, Padial LR, McDonnell LA, Vivanco F, Alvarez-Llamas G Abstract The molecular anatomy of healthy and atherosclerotic tissue is pursued here to identify ongoing molecular changes in atherosclerosis development. Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. Mass Spectrometry Imaging (MSI) is a novel unexplored ex vivo imaging approach in CVD able to provide in-tissue molecular maps. A rabbit model of early atherosclerosis was developed and high-spatial-resolution MALDI-MSI was applied to comparatively analyze histologically-based arterial regions of interest from control and early atherosclerotic aortas. Specific protocols were applied to identify lipids and proteins significantly altered in response to atherosclerosis. Observed protein alterations were confirmed by immunohistochemistry in rabbit tissue, and additionally in human aortas. Molecular features specifically defining different arterial regions were identified. Localized in the intima, increased expression of SFA and lysolipids and intimal spatial organization showing accumulation of PI, PG and SM point to endothelial dysfunction and triggered inflammatory response. TG, PA, SM and PE-Cer were identified specifically located in calcified regions. Thymosin β4 (TMSB4X) protein was upregulated in intima versus media layer and also in response to atherosclerosis. This overexpression and localization was confirmed in human aortas. In conclusion, molecular histology by MS Imaging identifies spatial organization of arterial tissue in response to atherosclerosis. PMID: 26079611 [PubMed - as supplied by publisher]

DNA barcoding: an efficient tool to overcome authentication challenges in the herbal market.

Wed, 17/06/2015 - 14:16
DNA barcoding: an efficient tool to overcome authentication challenges in the herbal market. Plant Biotechnol J. 2015 Jun 16; Authors: Mishra P, Kumar A, Nagireddy A, Mani DN, Shukla AK, Tiwari R, Sundaresan V Abstract The past couple of decades have witnessed global resurgence of herbal-based health care. As a result, the trade of raw drugs has surged globally. Accurate and fast scientific identification of the plant(s) is the key to success for the herbal drug industry. The conventional approach is to engage an expert taxonomist, who uses a mix of traditional and modern techniques for precise plant identification. However, for bulk identification at industrial scale, the process is protracted and time-consuming. DNA barcoding, on the other hand, offers an alternative and feasible taxonomic tool box for rapid and robust species identification. For the success of DNA barcode, the barcode loci must have sufficient information to differentiate unambiguously between closely related plant species and discover new cryptic species. For herbal plant identification, matK, rbcL, trnH-psbA, ITS, trnL-F, 5S-rRNA and 18S-rRNA have been used as successful DNA barcodes. Emerging advances in DNA barcoding coupled with next-generation sequencing and high-resolution melting curve analysis have paved the way for successful species-level resolution recovered from finished herbal products. Further, development of multilocus strategy and its application has provided new vistas to the DNA barcode-based plant identification for herbal drug industry. For successful and acceptable identification of herbal ingredients and a holistic quality control of the drug, DNA barcoding needs to work harmoniously with other components of the systems biology approach. We suggest that for effectively resolving authentication challenges associated with the herbal market, DNA barcoding must be used in conjunction with metabolomics along with need-based transcriptomics and proteomics. PMID: 26079154 [PubMed - as supplied by publisher]

Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming.

Wed, 17/06/2015 - 14:16
Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming. Int J Biol Sci. 2015;11(7):726-36 Authors: Li HH, Wang YW, Chen R, Zhou B, Ashwell JD, Fornace AJ Abstract Ionizing radiation has a variety of acute and long-lasting adverse effects on the immune system. Whereas measureable effects of radiation on immune cell cytotoxicity and population change have been well studied in human and animal models, little is known about the functional alterations of the surviving immune cells after ionizing radiation. The objective of this study was to delineate the effects of radiation on T cell function by studying the alterations of T cell receptor activation and metabolic changes in activated T cells isolated from previously irradiated animals. Using a global metabolomics profiling approach, for the first time we demonstrate that ionizing radiation impairs metabolic reprogramming of T cell activation, which leads to substantial decreases in the efficiency of key metabolic processes required for activation, such as glucose uptake, glycolysis, and energy metabolism. In-depth understanding of how radiation impacts T cell function highlighting modulation of metabolism during activation is not only a novel approach to investigate the pivotal processes in the shift of T cell homeostasis after radiation, it also may lead to new targets for therapeutic manipulation in the combination of radiotherapy and immune therapy. Given that appreciable effects were observed with as low as 10 cGy, our results also have implications for low dose environmental exposures. PMID: 26078715 [PubMed - in process]

Functional divergence of diterpene syntheses in the medicinal plant Salvia miltiorrhiza Bunge.

Wed, 17/06/2015 - 14:16
Functional divergence of diterpene syntheses in the medicinal plant Salvia miltiorrhiza Bunge. Plant Physiol. 2015 Jun 15; Authors: Cui G, Duan L, Jin B, Qian J, Xue Z, Shen G, Snyder JH, Song J, Chen S, Huang L, Peters RJ, Qi X Abstract The medicinal plant Salvia miltiorrhiza produces various tanshinone diterpenoids that have pharmacological activities such as vasorelaxation, against ischemia-reperfusion injury, and antiarrhythmic effects. Their biosynthesis is initiated from the general diterpenoid precursor (E,E,E)-geranylgeranyl diphosphate by sequential reactions catalyzed by copalyl diphosphate synthase (CPS) and kaurene synthase-like (KSL) cyclases. Here is reported characterization of these enzymatic families from S. miltiorrhiza, which has led to the identification of novel pathways, including roles for separate CPSs in tanshinone production in roots versus aerial tissues (SmCPS1 and SmCPS2, respectively), as well as the novel production of ent-13-epi-manoyl oxide by SmCPS4 and SmKSL2 in floral sepals. The conserved SmCPS5 is involved in gibberellin plant hormone biosynthesis. Down-regulation of SmCPS1 by RNAi resulted in substantial reduction of tanshinones, and metabolomics analysis revealed 21 potential intermediates, indicating a complex network for tanshinone metabolism defined by certain key biosynthetic steps. Notably, the correlation between conservation pattern and stereochemical product outcome of the CPSs observed here, suggests a degree of correlation that, especially when combined with the identity of certain key residues, may be predictive. Accordingly, this study provides molecular insights into the evolutionary diversification of functional diterpenoids in plants. PMID: 26077765 [PubMed - as supplied by publisher]

NMR metabolomics show evidence for mitochondrial oxidative stress in a mouse model of polycystic ovary syndrome.

Wed, 17/06/2015 - 14:16
NMR metabolomics show evidence for mitochondrial oxidative stress in a mouse model of polycystic ovary syndrome. J Proteome Res. 2015 Jun 16; Authors: Selen ES, Bolandnazar Z, Tonelli M, Bütz DE, Haviland JA, Porter WP, Assadi-Porter FM Abstract Polycystic ovary syndrome (PCOS) is associated with metabolic and endocrine disorders in women of reproductive age. The etiology of PCOS is still unknown. Mice prenatally treated with glucocorticoids exhibit metabolic disturbances that are similar to those seen in PCOS women. We used an untargeted nuclear magnetic resonance (NMR)-based metabolomics approach to understand the metabolic changes occurring in the plasma and kidney over time in female glucocorticoid treated (GC-treated) mice. There were significant changes in plasma amino acid levels (valine, tyrosine, and proline), and their intermediates (2-hydroxybutyrate, 4-aminobutyrate, taurine), whereas in kidneys, the TCA cycle metabolism (citrate, fumarate and succinate), and the pentose phosphate (PP) pathway products (inosine and uracil) are changed significantly (p<0.05) from 8 to 16 weeks of age. Levels of NADH, NAD+, NAD+/NADH, and NADH redox in kidneys indicate increased mitochondrial oxidative stress from 8 to 16 weeks in GC-treated mice. These results indicate that altered metabolic substrates in plasma and kidney of treated mice are associated with altered amino acid metabolism, increased cytoplasmic PP, and increased mitochondrial activity leading to a more oxidized state. This study identifies biomarkers associated with metabolic dysfunction in kidney mitochondria of the prenatal gluococorticoid treated mouse model of PCOS that may be used as an early predictive biomarker of oxidative stress in the PCOS metabolic disorder in women. PMID: 26076986 [PubMed - as supplied by publisher]

Roux-en-Y gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the presence of type 2 diabetes.

Wed, 17/06/2015 - 14:16
Related Articles Roux-en-Y gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the presence of type 2 diabetes. Diabetes Care. 2014 Dec;37(12):3150-6 Authors: Lips MA, Van Klinken JB, van Harmelen V, Dharuri HK, 't Hoen PA, Laros JF, van Ommen GJ, Janssen IM, Van Ramshorst B, Van Wagensveld BA, Swank DJ, Van Dielen F, Dane A, Harms A, Vreeken R, Hankemeier T, Smit JW, Pijl H, Willems van Dijk K Abstract OBJECTIVE: Obesity and type 2 diabetes mellitus (T2DM) have been associated with increased levels of circulating branched-chain amino acids (BCAAs) that may be involved in the pathogenesis of insulin resistance. However, weight loss has not been consistently associated with the reduction of BCAA levels. RESEARCH DESIGN AND METHODS: We included 30 obese normal glucose-tolerant (NGT) subjects, 32 obese subjects with T2DM, and 12 lean female subjects. Obese subjects underwent either a restrictive procedure (gastric banding [GB], a very low-calorie diet [VLCD]), or a restrictive/bypass procedure (Roux-en-Y gastric bypass [RYGB] surgery). Fasting blood samples were taken for the determination of amine group containing metabolites 4 weeks before, as well as 3 weeks and 3 months after the intervention. RESULTS: BCAA levels were higher in T2DM subjects, but not in NGT subjects, compared with lean subjects. Principal component (PC) analysis revealed a concise PC consisting of all BCAAs, which showed a correlation with measures of insulin sensitivity and glucose tolerance. Only after the RYGB procedure, and at both 3 weeks and 3 months, were circulating BCAA levels reduced. CONCLUSIONS: Our data confirm an association between deregulation of BCAA metabolism in plasma and insulin resistance and glucose intolerance. Three weeks after undergoing RYGB surgery, a significant decrease in BCAAs in both NGT as well as T2DM subjects was observed. After 3 months, despite inducing significant weight loss, neither GB nor VLCD induced a reduction in BCAA levels. Our results indicate that the bypass procedure of RYGB surgery, independent of weight loss or the presence of T2DM, reduces BCAA levels in obese subjects. PMID: 25315204 [PubMed - indexed for MEDLINE]

Metabolomic profiling of human serum in lung cancer patients using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry and gas chromatography/mass spectrometry.

Wed, 17/06/2015 - 14:16
Related Articles Metabolomic profiling of human serum in lung cancer patients using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry and gas chromatography/mass spectrometry. J Cancer Res Clin Oncol. 2015 Apr;141(4):705-18 Authors: Chen Y, Ma Z, Li A, Li H, Wang B, Zhong J, Min L, Dai L Abstract PURPOSE: Lung cancer is one of the most common causes of death from cancer. Serum markers that enable diagnosis of the disease in the early stage have not been found. METHODS: Serum samples were collected from 30 healthy volunteers and from 30 lung cancer patients preoperatively and postoperatively. Samples were subjected to metabolomic analysis using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry and gas chromatography/mass spectrometry. Differences in metabolomic profiles among the three groups were characterized by multivariate statistical techniques such as principal components analysis and partial least squares discriminant analysis (PLS-DA). An independent t test was used to determine whether levels of biomarker candidates identified using PLS-DA modeling were significantly different among groups at the univariate analysis level (p < 0.05). RESULTS: Based on pattern recognition results and univariate analysis, we showed that levels of ten potential biomarkers in serum were significantly different in the preoperative lung cancer patients compared with healthy volunteers and/or the postoperative lung cancer patients. The levels of sphingosine, phosphorylcholine, glycerophospho-N-arachidonoyl ethanolamine, γ-linolenic acid, 9,12-octadecadienoic acid, oleic acid, and serine were significantly different in preoperative lung cancer patients compared to healthy volunteers and to postoperative lung cancer patients. For prasterone sulfate, α-hydroxyisobutyric acid, 2,3,4-trihydroxybutyric acid, the levels were statistically different in preoperative and postoperative lung cancer patients compared with the healthy volunteers. CONCLUSIONS: Our study identified potential metabolic biomarkers for diagnosis of lung cancer. PMID: 25293627 [PubMed - indexed for MEDLINE]

Changes in urinary metabolic profile after oral administration of curcuma extract in rats.

Wed, 17/06/2015 - 14:16
Related Articles Changes in urinary metabolic profile after oral administration of curcuma extract in rats. J Pharm Biomed Anal. 2014 Nov;100:348-56 Authors: Dall'Acqua S, Stocchero M, Clauser M, Boschiero I, Ndoum E, Schiavon M, Mammi S, Schievano E Abstract The diffusion of phytochemicals in health promoting products is growing, but studies related to their effects on healthy subjects are still lacking despite the large consumption of natural products as nutraceuticals or food supplements. In many cases, research supports the in vitro antioxidant activity of phytochemicals, but the health claims attributed to the final marketed nutraceutical products have dubious scientific foundation. Also, studies focussed on the definition of their biological targets and mechanisms of action can be useful to assess their efficacy and safety. In this study, the effect of oral administration of 80mg/kg of Curcuma longa Linn. extract to 12 healthy rats over 25 days was evaluated by monitoring the changes of urinary composition. 24-h urine was collected during the animal experiment and the composition was analyzed by (1)H NMR and HPLC-MS. The two datasets were studied individually through a metabolomic approach and the multivariate analysis revealed significant differences between the control and the treated group. Curcumin levels were also measured in 24-h urine samples by HPLC-MS. Both the (1)H NMR and the HPLC-MS dataset showed that the administration of 80mg/kg of Curcuma longa extract to healthy animals induces changes in urinary composition. Decreased allantoin urinary levels can be considered a partial demonstration of the in vivo effect of curcumin on oxidative stress in a healthy animal model. PMID: 25200426 [PubMed - indexed for MEDLINE]

Genomics of ageing in twins.

Wed, 17/06/2015 - 14:16
Related Articles Genomics of ageing in twins. Proc Nutr Soc. 2014 Nov;73(4):526-31 Authors: Mangino M Abstract Ageing is a complex multifactorial process, reflecting the progression of all degenerative pathways within an organism. Due to the increase of life expectancy, in recent years, there is a pressing need to identify early-life events and risk factors that determine health outcomes in later life. So far, genetic variation only explains ~20-25 % of the variability of human survival to age 80+. This clearly implies that other factors (environmental, epigenetic and lifestyle) contribute to lifespan and the rate of healthy ageing within an individual. Twin studies in the past two decades proved to be a very powerful tool to discriminate the genetic from the environmental component. The aim of this review is to describe the basic concepts of the twin study design and to report some of the latest studies in which high-throughput technologies (e.g. genome/epigenome-wide assay, next generation sequencing, MS metabolic profiling) combined with the classical twin design have been applied to the analysis of novel 'omics' to further understand the molecular mechanisms of human ageing. PMID: 24984159 [PubMed - indexed for MEDLINE]

[Preliminary study on the discrimination of oral mucosa pathogens Saccharomyces with metabonomics method].

Wed, 17/06/2015 - 14:16
Related Articles [Preliminary study on the discrimination of oral mucosa pathogens Saccharomyces with metabonomics method]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2013 Jun;31(3):291-3, 299 Authors: Li M, Zhang X, Si Q Abstract OBJECTIVE: To evaluate the feasibility of identifying oral mucosa pathogenic bacteria by comparing the metabolic profiling of Saccharomyces and try to find a convenient and rapid way to discriminate oral micro-organisms. METHODS: Saccharomyces albicans ATCC 10231 and Saccharomyces tropicalis ATCC 13803 and Saccharomyces glabrata ATCC 15126 were respectively inoculated in sabouraud medium. The growth quantity were measured periodically by a spectrophotometer. And the growth curves of the inoculated bacteria were completed. The culture solutions in stationary phases of the three bacteria were respectively tested with 'H-nuclear magnetic resonance(1H-NMR) spectroscopy. The data of 1H-NMR spectroscopy results were analyzed by principal components analysis (PCA). RESULTS: The PCA showed respectively a obvious clustering phenomena and the points of every two groups' data stayed separately. Therefore, the NMR-based metabonomics profiles could discriminate the three kinds of mucosa pathogenic bacteria. CONCLUSION: The metabonomics can be expected to be a kind of promising useful method in quick discrimination of oral pathogenic bacteria. PMID: 23841304 [PubMed - indexed for MEDLINE]

Keratotic follicular plugs with calcifications in Conradi-Hünermann-Happle syndrome: histologic, biochemical and genetic testing correlation.

Tue, 16/06/2015 - 13:43
Keratotic follicular plugs with calcifications in Conradi-Hünermann-Happle syndrome: histologic, biochemical and genetic testing correlation. Br J Dermatol. 2015 Jun 15; Authors: Leclerc-Mercier S, Dufernez F, Fraitag S, Coulombe J, Dompmartin A, Barreau M, Bozon D, Lamazière A, Bonnefont JP, Khalifa E, Bodemer C, Hadj-Rabia S Abstract Conradi-Hünermann-Happle Syndrome (CHH, chondrodysplasia punctata type 2, MIM#302960), is an extremely rare X-linked dominant disorder of cholesterol metabolism which is usually lethal in male fetuses. Phenotypic expression is variable.(1, 2) The classical phenotype associates skeletal defects (cranio-facial anomalies, short stature, shortened asymmetric limbs associated with epiphyseal stippling), ocular anomalies (congenital cataract, microphtalmia) and skin lesions. At birth, transient ichthyosiform erythroderma is reported followed by linear ichthyosis on Blaschko lines (Figure 1A). Follicular atrophoderma reminiscent of "orange peel" skin occurs in later life (Figure 1B). This article is protected by copyright. All rights reserved. PMID: 26075358 [PubMed - as supplied by publisher]

Inborn Errors of Metabolism: Advances in Diagnosis and Therapy.

Tue, 16/06/2015 - 13:43
Inborn Errors of Metabolism: Advances in Diagnosis and Therapy. JAMA Pediatr. 2015 Jun 15; Authors: Vernon HJ Abstract Inborn errors of metabolism (IEMs) are a large class of genetic disorders characterized by disruption of cellular biochemical functions. Although individual IEMs are rare, collectively they represent a large and diverse class of genetic conditions, with new disorders and disease mechanisms being described regularly. Advances in the understanding of the molecular and biochemical etiologies of many IEMs via modalities such as whole-exome sequencing and metabolomics have led to significant progress in detection and treatment in recent years. In this review, we examine the current state of newborn screening for IEMs, recent advances in therapy for IEMs (including glutaric aciduria type I, urea cycle disorders, mitochondrial disorders, and lysosomal storage disorders), and opportunities for further exploration and discovery. PMID: 26075348 [PubMed - as supplied by publisher]

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