PubMed

Metabolomics and physiological analyses reveal β-sitosterol as an important plant growth regulator inducing tolerance to water stress in white clover. Planta. 2019 Sep 21;: Authors: Li Z, Cheng B, Yong B, Liu T, Peng Y, Zhang X, Ma X, Huang L, Liu W, Nie G Abstract MAIN CONCLUSION: β-sitosterol influences amino acids, carbohydrates, organic acids, and other metabolite metabolism and homeostasis largely contributing to better tolerance to water stress in white clover. β-sitosterol (BS) could act as an important plant growth regulator when plants are subjected to harsh environmental conditions. Objective of this study was to examine effects of BS on growth and water stress tolerance in white clover based on physiological responses and metabolomics. White clover was pretreated with or without BS and then subjected to water stress for 7 days in controlled growth chambers. Physiological analysis demonstrated that exogenous application of BS (120 μM) could significantly improve stress tolerance associated with better growth performance and photosynthesis, higher leaf relative water content, and less oxidative damage in white clover in response to water stress. Metabolic profiling identified 78 core metabolites involved in amino acids, organic acids, sugars, sugar alcohols, and other metabolites in leaves of white clover. For sugars and sugar alcohol metabolism, the BS treatment enhanced the accumulation of fructose, glucose, maltose, and myo-inositol contributing to better antioxidant capacity, growth maintenance, and osmotic adjustment in white clover under water stress. The application of BS was inclined to convert glutamic acid into proline, 5-oxoproline, and chlorophyll instead of going to pyruvate and alanine; the BS treatment did not significantly affect intermediates of tricarboxylic acid cycle (citrate, aconitate, and malate), but promoted the accumulation of other organic acids including lactic acid, glycolic acid, glyceric acid, shikimic acid, galacturonic acid, and quinic acid in white clover subjected to water stress. In addition, cysteine, an important antioxidant metabolite, was also significantly improved by BS in white clover under water stress. These altered amino acids and organic acids metabolism could play important roles in growth maintenance and modulation of osmotic and redox balance against water stress in white clover. Current findings provide a new insight into BS-induced metabolic homeostasis related to growth and water stress tolerance in plants. PMID: 31542810 [PubMed - as supplied by publisher]

Metabolomics coupled with SystemsDock reveal the protective effect and the potential active components of Naozhenning granule against traumatic brain injury. J Ethnopharmacol. 2019 Sep 19;:112247 Authors: Cao J, Duan Y, Liu Y, Liu H, Wei C, Wang J, Qin X, Wang X, Li Z Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Naozhenning granule (NZN), a widely traditional Chinese medicine (TCM) prescription with a long history of clinical, which is mainly used in the treatment of concussion, cerebral post-traumatic syndrome, consists of Di Huang (Radix of Rehmannia glutinosa (Gaertn.) DC.), Dang Gui (Radix of Angelica sinensis (Oliv.) Diels), Chen Pi (Pericarpium of Citrus reticulata Blanco), Danshen (Radix of Salvia Miltiorrhiza Bunge.), Di Long (Pheretima aspergillum (E. Perrier)), Mu Dan Pi (Cortex of Paeonia suffruticosa Andrews), Suan Zao Ren (Semen of Ziziphus jujuba Mill.), Chuan Xiong (Rhizoma of Ligusticum striatum DC.), Zhu Ru (Phyllostachys nigra (Lodd. Ex Lindl.) Munro), Bai Zi Ren (Semen of Platycladus orientalis (L.) Franco) and Fu Ling (sclerotium of Poria cocos (Schw.)Wolf). AIM OF THE STUDY: This study aimed to unravel the mechanism and material basis of NZN against traumatic brain injury. MATERIALS AND METHODS: In this study, a 1H nuclear magnetic resonance (NMR) based metabolomic approach combined with systemsDock was employed to study the protective effect of NZN against traumatic brain injury using a cerebral concussion rat model. The morris water maze test and biochemical indexes were used to evaluate the efficacy of NZN. RESULTS: The results of morris water maze test suggested NZN can improve the spatial learning and memory of model rats, and the superoxide dismutas (SOD) and malonyldialdehyde (MDA) level indicated that the effect of NZN was related with the regulation of oxidative stress. Multivariate analysis revealed that the effect of NZN was related with regulation of 18 brain metabolites, and the corresponding metabolic pathways were further revealed by MetPA analysis. 13 serum absorbed components were found to hit the targets both related with the metabolic regulation and cerebral trauma through systemsDock-aided molecular docking experiments, and these compounds might be served as the active compounds in NZN against cerebral trauma. CONCLUSION: 1H-NMR based metabolomics and molecular docking provided the insights for the synergistic mechanisms and the potential active compounds of NZN in treating cerebral trauma. However, the bioactive compounds and their synergistic effect need to be further validated. PMID: 31542470 [PubMed - as supplied by publisher]

Comparative serum metabolomics between SCID mice and BALB/c mice with or without Schistosoma japonicum infection: clues to the abnormal growth and development of schistosome in SCID mice. Acta Trop. 2019 Sep 19;:105186 Authors: Liu R, Ye F, Zhong QP, Wang SH, Chai T, Dong HF, Ming Z Abstract The small blood flukes of genus Schistosoma, which cause one of the most prevalent and serious parasitic zoonosis schistosomiasis, are dependent on immune-related factors of their mammalian host to facilitate their growth and development, and the formation of granulomatous pathology caused by eggs deposited in host's liver and intestinal wall. Schistosome development is hampered in the mice lacking just T cells, and is even more heavily retarded in the severe combined immunodeficient (SCID) mice lacking both T and B lymphocytes. Nevertheless, it's still not clear about the underlying regulatory molecular mechanisms of schistosome growth and development by host's immune system. This study, therefore, detected and compared the serum metabolic profiles between the immunodeficient mice and immunocompetent mice (SCID mice vs. BALB/c mice) before and after S. japonicum infection (on the thirty-fifth day post infection using liquid chromatography-mass spectrometry (LC-MS). Totally, 705 ion features in electrospray ionization in positive-ion mode (ESI+) and 242 ion features in ESI- mode were identified, respectively. First, distinct serum metabolic profiles were identified between SCID mice and BALB/c mice without S. japonicum worms infection. Second, uniquely perturbed serum metabolites and their enriched pathways were also obtained between SCID mice and BALB/c mice after S. japonicum infection, which included differential metabolites due to both species differences and differential responses to S. japonicum infection. The metabolic pathways analysis revealed that arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, alpha-linolenic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and purine metabolism were enriched based on the differential serum metabolites between SCID mice and BALB/c mice after S. japonicum infection, which was addressed to be related to the retarded growth and development of S. japonicum in SCID mice. These findings provide new clues to the underlying molecular events of host's systemic metabolic changes on the growth and development of S. japonicum worms, and also provide quite promising candidates for exploitation of drugs or vaccines against schistosome and schistosomiasis. PMID: 31542371 [PubMed - as supplied by publisher]

Accumulation of sugars and nucleosides in response to high salt and butanol stress in 1-butanol producing Synechococcus elongatus. J Biosci Bioeng. 2019 Sep 18;: Authors: Fathima AM, Laviña WA, Putri SP, Fukusaki E Abstract 1-Butanol production using photosynthetic organisms such as cyanobacteria has garnered interest among researchers due to its high potential as a sustainable biofuel. Previously, the cyanobacterium Synechococcus elongatus PCC 7942 was engineered to produce 1-butanol through the introduction of a modified CoA-dependent pathway. S. elongatus strain DC11, a high producer of 1-butanol, was constructed based on metabolomics-assisted strain engineering. DC11 can reach a production titer of 418.7 mg/L in 6 days, cutting the production time in half compared to the previously constructed DC7. Regardless, the final 1-butanol titer of DC11 was still low compared to other microbial hosts. Sensitivity towards 1-butanol of the producing strain has been known as one of main hurdles for improving cyanobacterial production system. Thus, to improve cyanobacterial-based 1-butanol production in the future, we employed the metabolomics approach to study the intrinsic effect of improved 1-butanol productivity in DC11. This study focused on metabolite profiling of DC11 using LC/MS/MS. Results showed that there is an accumulation of disaccharide-P and sucrose/trehalose in DC11 compared to the DC7. These metabolites were previously reported to have a role in salt and alcohol stress response in cyanobacteria and therefore, DC11 was subjected to 0.2 M of NaCl and 1000 mg/L of 1-butanol for further investigation. DC11 with stress treatment showed a more prominent accumulation of sugars and nucleosides compared to control. The results obtained from this study may be beneficial for future strain improvement strategies in S. elongatus, particularly addressing the metabolic response of this strain upon 1-butanol stress. PMID: 31542348 [PubMed - as supplied by publisher]

Metabolic Profiling Associates with Disease Severity in Non-Ischemic Dilated Cardiomyopathy. J Card Fail. 2019 Sep 18;: Authors: Verdonschot JAJ, Wang P, van Bilsen M, Hazebroek MR, Merken JJ, Vanhoutte EK, Henkens MTHM, van den Wijngaard A, Glatz JFC, Krapels IPC, Brunner HG, Heymans SRB, Bierau J Abstract AIMS: Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in non-ischemic dilated cardiomyopathy (DCM) patients and compared its incremental value on top of NT-proBNP. METHODS AND RESULTS: A total of 149 metabolites were measured in plasma and urine samples of 273 DCM patients with different stages of disease (DCM patients with LVRR (normal LVEF), n=70; asymptomatic DCM, n=72 and symptomatic DCM, n=131). Acylcarnitines, sialic acid, and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by uni-biomarker linear regression, sPLSDA, Random Forest and conditional Random Forest analyses. However, the absolute difference of the metabolic profile among groups was marginal. A decision tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish DCM patients with LVRR from symptomatic DCM (AUC 0.813±0.138 versus 0.739±0.114; p=0.02). CONCLUSION: Functional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in non-ischemic DCM. PMID: 31541741 [PubMed - as supplied by publisher]

Related Articles Comparative metabolomic analysis reveals different evolutionary mechanisms for branched-chain amino acids production. Bioprocess Biosyst Eng. 2019 Sep 20;: Authors: Ma Q, Mo X, Zhang Q, Hou Z, Tan M, Xia L, Sun Q, Xie X, Chen N Abstract Evolution is a powerful tool for the breeding of microorganisms, while the connection between the changes of intracellular metabolism and different evolution directions is still unclear, which once clarified, will greatly expand the application of evolutionary engineering. We aim to clarify the correlation between metabolism changes and evolution directions in two Corynebacterium glutamicum strains for L-valine and L-leucine overproducing originated from the same parental strain by repeated random mutagenesis and selection. GC-MS metabolomics was performed to identify and quantify intracellular metabolites of the evolved and wild-type C. glutamicum strains. Time-series comparison of the fermentation processes was performed. The metabolism differences of three strains mainly exist in central carbon metabolism and the stress-resisting modes. C. glutamicum XV developed an overall "pyruvate-saving" mode for L-valine synthesis, and adopted a trehalose accumulating strategy to resist environmental stresses. C. glutamicum CP depended on an enhanced "pyruvate-producing" mode, together with certain "pyruvate-saving" strategies, for efficient L-leucine synthesis, and accumulated proline, my-inositol, and inositol as the stress-resisting measure. These elaborate regulation strategies could be used in future metabolic engineering, making evolution more informative and applicable. PMID: 31541312 [PubMed - as supplied by publisher]

Related Articles Compound danshen dripping pills normalize a reprogrammed metabolism of myocardial ischemia rats to interpret its time-dependent efficacy in clinic trials: a metabolomic study. Metabolomics. 2019 Sep 20;15(10):128 Authors: Aa N, Guo JH, Cao B, Sun RB, Ma XH, Chu Y, Zhou SP, Aa JY, Yang ZJ, Sun H, Wang GJ Abstract INTRODUCTION: Clinical trials of Compound danshen dripping pills (CDDP) indicated distinct improvement in patients with chronic stable angina. Daily fluctuation of therapeutic effect agreed with a peak-valley PK profile during a 4-week CDDP regimen, but stabilized after 8-week treatment. OBJECTIVES: This article aims to explore the underlying mechanism for the time-dependent drug efficacy of the up-down fluctuation or stabilization in clinic trials. METHODS: A rat model of myocardial ischemia was established via isoproterenol induction. Metabolomics was employed to analyze the energy-related substances both in circulatory system and myocardium in the myocardial ischemia model. RESULTS: CDDP treatment ameliorated myocardial ischemia, reversed the reprogramming of the metabolism induced by ISO and normalized the level of most myocardial substrates and the genes/enzymes associated with those metabolic changes. After 1- or 2-week treatment, CDDP regulated plasma and myocardial metabolome in an analogous, time-dependent way, and modulated metabolic patterns of ischemic rats that perfectly matched with the fluctuated or stabilized effects observed in clinical trials with 4 or 8-week treatment, respectively. CONCLUSION: Metabolic modulation by CDDP contributes to the fluctuated or stabilized therapeutic outcome, and is a potential therapeutic approach for myocardial ischemia diseases. PMID: 31541307 [PubMed - in process]

Related Articles Inflammation markers in the saliva of infants born from Zika-infected mothers: exploring potential mechanisms of microcephaly during fetal development. Sci Rep. 2019 Sep 20;9(1):13606 Authors: de Oliveira DN, Lima EO, Melo CFOR, Delafiori J, Guerreiro TM, Rodrigues RGM, Morishita KN, Silveira C, Muraro SP, de Souza GF, Vieira A, Silva A, Batista RF, Doriqui MJR, Sousa PS, Milanez GP, Proença-Módena JL, Cavalcanti DP, Catharino RR Abstract Zika virus (ZIKV) has emerged as one of the most medically relevant viral infections of the past decades; the devastating effects of this virus over the developing brain are a major matter of concern during pregnancy. Although the connection with congenital malformations are well documented, the mechanisms by which ZIKV reach the central nervous system (CNS) and the causes of impaired cortical growth in affected fetuses need to be better addressed. We performed a non-invasive, metabolomics-based screening of saliva from infants with congenital Zika syndrome (CZS), born from mothers that were infected with ZIKV during pregnancy. We were able to identify three biomarkers that suggest that this population suffered from an important inflammatory process; with the detection of mediators associated with glial activation, we propose that microcephaly is a product of immune response to the virus, as well as excitotoxicity mechanisms, which remain ongoing even after birth. PMID: 31541139 [PubMed - in process]

Related Articles Inactivation of NF-κB2 (p52) restrains hepatic glucagon response via preserving PDE4B induction. Nat Commun. 2019 Sep 20;10(1):4303 Authors: Zhang WS, Pan A, Zhang X, Ying A, Ma G, Liu BL, Qi LW, Liu Q, Li P Abstract Glucagon promotes hepatic gluconeogenesis and maintains whole-body glucose levels during fasting. The regulatory factors that are involved in fasting glucagon response are not well understood. Here we report a role of p52, a key activator of the noncanonical nuclear factor-kappaB signaling, in hepatic glucagon response. We show that p52 is activated in livers of HFD-fed and glucagon-challenged mice. Knockdown of p52 lowers glucagon-stimulated hyperglycemia, while p52 overexpression augments glucagon response. Mechanistically, p52 binds to phosphodiesterase 4B promoter to inhibit its transcription and promotes cAMP accumulation, thus augmenting the glucagon response through cAMP/PKA signaling. The anti-diabetic drug metformin and ginsenoside Rb1 lower blood glucose at least in part by inhibiting p52 activation. Our findings reveal that p52 mediates glucagon-triggered hepatic gluconeogenesis and suggests that pharmacological intervention to prevent p52 processing is a potential therapeutic strategy for diabetes. PMID: 31541100 [PubMed - in process]

Related Articles Differences in Pregnancy Metabolic Profiles and Their Determinants between White European and South Asian Women: Findings from the Born in Bradford Cohort. Metabolites. 2019 Sep 18;9(9): Authors: Taylor K, Ferreira DLS, West J, Yang T, Caputo M, Lawlor DA Abstract There is widespread metabolic disruption in women upon becoming pregnant. South Asians (SA) compared to White Europeans (WE) have more fat mass and are more insulin-resistant at a given body mass index (BMI). Whether these are reflected in other gestational metabolomic differences is unclear. Our aim was to compare gestational metabolic profiles and their determinants between WE and SA women. We used data from a United Kingdom (UK) cohort to compare metabolic profiles and associations of maternal age, education, parity, height, BMI, tricep skinfold thickness, gestational diabetes (GD), pre-eclampsia, and gestational hypertension with 156 metabolic measurements in WE (n = 4072) and SA (n = 4702) women. Metabolic profiles, measured in fasting serum taken between 26-28 weeks gestation, were quantified by nuclear magnetic resonance. Distributions of most metabolic measures differed by ethnicity. WE women had higher levels of most lipoprotein subclasses, cholesterol, glycerides and phospholipids, monosaturated fatty acids, and creatinine but lower levels of glucose, linoleic acid, omega-6 and polyunsaturated fatty acids, and most amino acids. Higher BMI and having GD were associated with higher levels of several lipoprotein subclasses, triglycerides, and other metabolites, mostly with stronger associations in WEs. We have shown differences in gestational metabolic profiles between WE and SA women and demonstrated that associations of exposures with these metabolites differ by ethnicity. PMID: 31540515 [PubMed]

Related Articles Comparative Evaluation of Six Traditional Fermented Soybean Products in East Asia: A Metabolomics Approach. Metabolites. 2019 Sep 13;9(9): Authors: Kwon YS, Lee S, Lee SH, Kim HJ, Lee CH Abstract Many ethnic fermented soybean products (FSPs) have long been consumed as seasoning and protein sources in East Asia. To evaluate the quality of various FSPs in East Asia, non-targeted metabolite profiling with multivariate analysis of six traditional FSPs (Natto; NT, Cheonggukjang; CG, Doenjang; DJ, Miso; MS, Doubanjiang; DB, Tianmianjiang; TM) was performed. Six FSPs could be clearly distinguished by principle component analysis (PCA) and partial least square-discriminant analysis (PLS-DA). Amino acid contents were relatively higher in NT and CG, sugar and sugar alcohol contents were relatively higher in MS and TM, isoflavone glycoside contents were relatively highest in CG, isoflavone aglycon contents were the highest in DJ, and soyasaponin contents were the highest in CG. Antioxidant activity and physicochemical properties were determined to examine the relationships between the FSPs and their antioxidant activities. We observed a negative correlation between isoflavone aglycon contents and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) activity. Furthermore, the order of ABTS activity of FSPs has a positive correlation with the order of soybean content in the six FSPs. Herein it was found that primary metabolites were affected by the main ingredients and secondary metabolites were most influenced by the fermentation time, and that soybean content contributed more to antioxidant activity than fermentation time. PMID: 31540263 [PubMed]

Related Articles Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients. Metabolites. 2019 Sep 14;9(9): Authors: Ahonen L, Jäntti S, Suvitaival T, Theilade S, Risz C, Kostiainen R, Rossing P, Orešič M, Hyötyläinen T Abstract Several small molecule biomarkers have been reported in the literature for prediction and diagnosis of (pre)diabetes, its co-morbidities, and complications. Here, we report the development and validation of a novel, quantitative method for the determination of a selected panel of 34 metabolite biomarkers from human plasma. We selected a panel of metabolites indicative of various clinically-relevant pathogenic stages of diabetes. We combined these candidate biomarkers into a single ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method and optimized it, prioritizing simplicity of sample preparation and time needed for analysis, enabling high-throughput analysis in clinical laboratory settings. We validated the method in terms of limits of detection (LOD) and quantitation (LOQ), linearity (R2), and intra- and inter-day repeatability of each metabolite. The method's performance was demonstrated in the analysis of selected samples from a diabetes cohort study. Metabolite levels were associated with clinical measurements and kidney complications in type 1 diabetes (T1D) patients. Specifically, both amino acids and amino acid-related analytes, as well as specific bile acids, were associated with macro-albuminuria. Additionally, specific bile acids were associated with glycemic control, anti-hypertensive medication, statin medication, and clinical lipid measurements. The developed analytical method is suitable for robust determination of selected plasma metabolites in the diabetes clinic. PMID: 31540069 [PubMed]

Related Articles Altered Metabolomic Profile in Patients with Peripheral Artery Disease. J Clin Med. 2019 Sep 14;8(9): Authors: Ismaeel A, Franco ME, Lavado R, Papoutsi E, Casale GP, Fuglestad M, Mietus CJ, Haynatzki GR, Smith RS, Bohannon WT, Sawicki I, Pipinos II, Koutakis P Abstract Peripheral artery disease (PAD) is a common atherosclerotic disease characterized by narrowed or blocked arteries in the lower extremities. Circulating serum biomarkers can provide significant insight regarding the disease progression. Here, we explore the metabolomics signatures associated with different stages of PAD and investigate potential mechanisms of the disease. We compared the serum metabolites of a cohort of 26 PAD patients presenting with claudication and 26 PAD patients presenting with critical limb ischemia (CLI) to those of 26 non-PAD controls. A difference between the metabolite profiles of PAD patients from non-PAD controls was observed for several amino acids, acylcarnitines, ceramides, and cholesteryl esters. Furthermore, our data demonstrate that patients with CLI possess an altered metabolomic signature different from that of both claudicants and non-PAD controls. These findings provide new insight into the pathophysiology of PAD and may help develop future diagnostic procedures and therapies for PAD patients. PMID: 31540015 [PubMed]

Related Articles Twenty-Eight Fungal Secondary Metabolites Detected in Pig Feed Samples: Their Occurrence, Relevance and Cytotoxic Effects In Vitro. Toxins (Basel). 2019 Sep 14;11(9): Authors: Novak B, Rainer V, Sulyok M, Haltrich D, Schatzmayr G, Mayer E Abstract Feed samples are frequently contaminated by a wide range of chemically diverse natural products, which can be determined using highly sensitive analytical techniques. Next to already well-investigated mycotoxins, unknown or unregulated fungal secondary metabolites have also been found, some of which at significant concentrations. In our study, 1141 pig feed samples were analyzed for more than 800 secondary fungal metabolites using the same LC-MS/MS method and ranked according to their prevalence. Effects on the viability of the 28 most relevant were tested on an intestinal porcine epithelial cell line (IPEC-J2). The most frequently occurring compounds were determined as being cyclo-(L-Pro-L-Tyr), moniliformin, and enniatin B, followed by enniatin B1, aurofusarin, culmorin, and enniatin A1. The main mycotoxins, deoxynivalenol and zearalenone, were found only at ranks 8 and 10. Regarding cytotoxicity, apicidin, gliotoxin, bikaverin, and beauvericin led to lower IC50 values, between 0.52 and 2.43 µM, compared to deoxynivalenol (IC50 = 2.55 µM). Significant cytotoxic effects were also seen for the group of enniatins, which occurred in up to 82.2% of the feed samples. Our study gives an overall insight into the amount of fungal secondary metabolites found in pig feed samples compared to their cytotoxic effects in vitro. PMID: 31540008 [PubMed - in process]

Related Articles Comparative molecular and metabolic responses of wheat seedlings (Triticum aestivum L.) to the imazethapyr enantiomers S-IM and R-IM. Sci Total Environ. 2019 Nov 20;692:723-731 Authors: Qu Q, Zhang Z, Li Y, Zhou Z, Ye Y, Lu T, Sun L, Qian H Abstract The enantioselective effects of imazethapyr (IM) enantiomers on wheat seedlings in a hydroponic medium were studied. R-IM at 0.05mg/L exerted a stronger inhibitory effect on shoot weight and root weight than 0.05mg/L S-IM, suggesting that R-IM more severely inhibited growth. Oxidative damage, based on the anthocyanin content, malondialdehyde (MDA) content, antioxidant enzyme activities and transcript levels of antioxidant enzyme genes, were studied together with the cellular ultrastructure of wheat leaves. The anthocyanin and MDA contents in the R-IM treatment group were significantly increased compared with those in the control group, but no significant changes were observed in the S-IM treatment group. The antioxidant enzyme activities of CAT and SOD were inhibited by 0.32- and 0.73-fold, respectively, in the 14day R-IM treatment group compared to those in the control. However, the transcript levels of antioxidant enzyme genes, including CuZnSOD, POD and CAT, were downregulated in the 14day R-IM exposure group, but those of DHAR were not. The number and size of starch granules increased and chloroplast swelling was observed in wheat leaf cells after R-IM exposure, which showed that photosynthetic functions were potentially disturbed. These results directly or indirectly imply that R-IM exposure causes more oxidative stress and exerts a stronger negative effect on wheat than S-IM. A metabolomics approach revealed that the tricarboxylic acid cycle was heavily suppressed by R-IM treatment. Some amino acids (proline, threonine, lysine, valine) were increased by only the R-IM treatment, indicating the activation of antioxidant pathways. The decrease in a series of fatty acids implied that the cell membrane composition changed in response to R-IM. These results provide a deeper understanding of the enantioselective effects of IM enantiomers on the molecular and metabolic responses in wheat seedlings. PMID: 31539980 [PubMed - in process]

Different forms of nitrogen application affect metabolite patterns in grapevine leaves and the sensory of wine. Plant Physiol Biochem. 2019 Sep 11;143:308-319 Authors: Lang CP, Merkt N, Klaiber I, Pfannstiel J, Zörb C Abstract The quality of grapevine berries, must and wine is influenced by environmental and viticultural inputs and their complex interactions. Aroma and flavour are decisive for quality and are mainly determined by primary and secondary metabolites. In particular, phenolic compounds contribute to berry and wine quality. The influence of various nitrogen forms on i) the composition of phenolic compounds in leaves and wine and; ii) the resulting wine quality were studied in a vineyard system. Must and wine quality was evaluated by chemical analysis and sensory testing. Metabolomic profiling was also performed. Aroma and sensory profile were significantly changed by the application of nitrogen in contrast to no nitrogen fertilisation. The levels of 33 metabolites in leaves and 55 metabolites in wine were significantly changed altered by fertilisation with the various nitrogen forms. In leaves, more metabolites were increased by the use of calcium nitrate or ammonium but were decreased by the use of urea. In terms of wine, the used nitrogen forms decreased more metabolites compared with no fertilisation. PMID: 31539760 [PubMed - as supplied by publisher]

Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China. JAMA Netw Open. 2019 Sep 04;2(9):e1911970 Authors: Seow WJ, Shu XO, Nicholson JK, Holmes E, Walker DI, Hu W, Cai Q, Gao YT, Xiang YB, Moore SC, Bassig BA, Wong JYY, Zhang J, Ji BT, Boulangé CL, Kaluarachchi M, Wijeyesekera A, Zheng W, Elliott P, Rothman N, Lan Q Abstract Importance: Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood. Objective: To assess the association between metabolomics and lung cancer risk among never-smoking women. Design, Setting, and Participants: This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018. Exposures: Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured. Main Outcomes and Measures: Incident lung cancer. Results: Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odds ratio for second tertile, 0.52 [95% CI, 0.34-0.80]; and odds ratio for third tertile, 0.46 [95% CI, 0.30-0.70]), and the association was consistent across different histological subtypes and follow-up times. Additionally, metabolic pathway analysis found several systemic biological alterations that were associated with lung cancer risk, including 1-carbon metabolism, nucleotide metabolism, oxidative stress, and inflammation. Conclusions and Relevance: This prospective study of the untargeted urinary metabolome and lung cancer among never-smoking women in China provides support for the hypothesis that soy-based metabolites are associated with lower lung cancer risk in never-smoking women and suggests that biological processes linked to air pollution may be associated with higher lung cancer risk in this population. PMID: 31539079 [PubMed - in process]

Related Articles The omics approach to bee nutritional landscape. Metabolomics. 2019 Sep 20;15(10):127 Authors: Chakrabarti P, Morré JT, Lucas HM, Maier CS, Sagili RR Abstract BACKGROUND: Significant annual honey bee colony losses have been reported in the USA and across the world over the past years. Malnutrition is one among several causative factors for such declines. Optimal nutrition serves as the first line of defense against multiple stressors such as parasites/pathogens and pesticides. Given the importance of nutrition, it is imperative to understand bee nutrition holistically, identifying dietary sources that may fulfill bee nutritional needs. Pollen is the primary source of protein for bees and is critical for brood rearing and colony growth. Currently, there is significant gap in knowledge regarding the chemical and nutritional composition of pollen. METHODS: Targeted sterol analysis and untargeted metabolomics were conducted on five commercially available crop pollens, three bee-collected crop pollens, three vegetable oils (often added to artificial protein supplements by beekeepers), and one commonly used artificial protein supplement. RESULTS: This study reports key phytosterols and metabolites present across a spectrum of bee diets, including some of the major bee-pollinated crop pollens in the western United States. Significant differences were observed in sterol concentrations among the dietary sources tested. Among all quantified sterols, the highest concentrations were observed for 24-methylenecholesterol and further, pollen samples exhibited the highest 24-methylenecholesterol among all diet sources that were tested. Also, 236 metabolites were identified across all dietary sources examined. CONCLUSION: Information gleaned from this study is crucial in understanding the nutritional landscape available to all bee pollinators and may further assist in future efforts to develop comprehensive database of nutrients and metabolites present in all bee diets. PMID: 31538263 [PubMed - in process]

Related Articles MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle associated with early onset severe encephalopathy. Hum Genet. 2019 Sep 19;: Authors: Broeks MH, Shamseldin HE, Alhashem A, Hashem M, Abdulwahab F, Alshedi T, Alobaid I, Zwartkruis F, Westland D, Fuchs S, Verhoeven-Duif NM, Jans JJM, Alkuraya FS Abstract The reversible oxidation of L-malate to oxaloacetate is catalyzed by NAD(H)-dependent malate dehydrogenase (MDH). MDH plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle. These metabolic processes are important in mitochondrial NADH supply for oxidative phosphorylation. Recently, bi-allelic mutations in mitochondrial MDH2 were identified in patients with global developmental delay, epilepsy and lactic acidosis. We now report two patients from an extended consanguineous family with a deleterious variant in the cytosolic isoenzyme of MDH (MDH1). The homozygous missense variant in the NAD+-binding domain of MDH1 led to severely diminished MDH protein expression. The patients presented with global developmental delay, epilepsy and progressive microcephaly. Both patients had normal concentrations of plasma amino acids, acylcarnitines, lactate, and urine organic acids. To identify the metabolic consequences of MDH1 deficiency, untargeted metabolomics was performed on dried blood spots (DBS) from the patients and in MDH1 knockout HEK293 cells that were generated by Crispr/Cas9. Increased levels of glutamate and glycerol-3-phosphate were found in DBS of both patients. In MDH1 KO HEK293 cells, increased levels of glycerol-3-phosphate were also observed, as well as increased levels of aspartate and decreased levels of fumarate. The consistent finding of increased concentrations of glycerol-3-phosphate may represent a compensatory mechanism to enhance cytosolic oxidation of NADH by the glycerol-P-shuttle. In conclusion, MDH1 deficiency is a new metabolic defect in the malate-aspartate shuttle characterized by a severe neurodevelopmental phenotype with elevated concentrations of glycerol-3-phosphate as a potential biomarker. PMID: 31538237 [PubMed - as supplied by publisher]

Related Articles Biobanking for discovery of novel cardiovascular biomarkers using imaging-quantified disease burden: protocol for the longitudinal, prospective, BioHEART-CT cohort study. BMJ Open. 2019 Sep 18;9(9):e028649 Authors: Kott KA, Vernon ST, Hansen T, Yu C, Bubb KJ, Coffey S, Sullivan D, Yang J, O'Sullivan J, Chow C, Patel S, Chong J, Celermajer DS, Kritharides L, Grieve SM, Figtree GA Abstract INTRODUCTION: Coronary artery disease (CAD) persists as a major cause of morbidity and mortality worldwide despite intensive identification and treatment of traditional risk factors. Data emerging over the past decade show a quarter of patients have disease in the absence of any known risk factor, and half have only one risk factor. Improvements in quantification and characterisation of coronary atherosclerosis by CT coronary angiography (CTCA) can provide quantitative measures of subclinical atherosclerosis-enhancing the power of unbiased 'omics' studies to unravel the missing biology of personal susceptibility, identify new biomarkers for early diagnosis and to suggest new targeted therapeutics. METHODS AND ANALYSIS: BioHEART-CT is a longitudinal, prospective cohort study, aiming to recruit 5000 adult patients undergoing clinically indicated CTCA. After informed consent, patient data, blood samples and CTCA imaging data are recorded. Follow-up for all patients is conducted 1 month after recruitment, and then annually for the life of the study. CTCA data provide volumetric quantification of total calcified and non-calcified plaque, which will be assessed using established and novel scoring systems. Comprehensive molecular phenotyping will be performed using state-of-the-art genomics, metabolomics, proteomics and immunophenotyping. Complex network and machine learning approaches will be applied to biological and clinical datasets to identify novel pathophysiological pathways and to prioritise new biomarkers. Discovery analysis will be performed in the first 1000 patients of BioHEART-CT, with validation analysis in the following 4000 patients. Outcome data will be used to build improved risk models for CAD. ETHICS AND DISSEMINATION: The study protocol has been approved by the human research ethics committee of North Shore Local Health District in Sydney, Australia. All findings will be published in peer-reviewed journals or at scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001322224. PMID: 31537558 [PubMed - in process]