PubMed

Multiplex Biomarker Approaches in Type 2 Diabetes Mellitus Research. Methods Mol Biol. 2017;1546:37-55 Authors: Ozanne SE, Rahmoune H, Guest PC Abstract Type 2 diabetes mellitus is a multifactorial condition resulting in high fasting blood glucose levels. Although its diagnosis is straightforward, there is not one set of biomarkers or drug targets that can be used for classification or personalized treatment of individuals who suffer from this condition. Instead, the application of multiplex methods incorporating a systems biology approach is essential in order to increase our understanding of this disease. This chapter reviews the state of the art in biomarker studies of human type 2 diabetes from a proteomic and metabolomic perspective. Our main focus was on biomarkers for disease prediction as these could lead to early intervention strategies for the best possible patient outcomes. PMID: 27896756 [PubMed - in process]

Application of Multiplex Biomarker Approaches to Accelerate Drug Discovery and Development. Methods Mol Biol. 2017;1546:3-17 Authors: Rahmoune H, Guest PC Abstract Multiplex biomarker tests are becoming an essential part of the drug development process. This chapter explores the role of biomarker-based tests as effective tools in improving preclinical research and clinical development, and the challenges that this presents. The potential of incorporating biomarkers in the clinical pipeline to improve decision making, accelerate drug development, improve translation, and reduce development costs is discussed. This chapter also discusses the latest biomarker technologies in use to make this possible and details the next steps that must undertaken to keep driving this process forwards. PMID: 27896754 [PubMed - in process]

High-throughput metabolomics approach reveals new mechanistic insights for drug response of phenotypes of geniposide towards alcohol-induced liver injury by using liquid chromatography coupled to high resolution mass spectrometry. Mol Biosyst. 2016 Nov 29; Authors: Zhang T, Zhang A, Qiu S, Sun H, Han Y, Guan Y, Wang X Abstract Alcohol-induced liver injury (ALD) shows obvious metabolic disorders, categorized by a wide range of metabolite abnormalities. High-throughput metabolomics technology appears to be an appropriate solution. In this study, a urine metabolic profile was assessed using a UPLC-Q-TOF/HDMS (liquid chromatography coupled to high resolution mass spectrometry) approach to investigate the underlying molecular mechanisms of ALD and the therapeutic effect of geniposide. The endogenous low-molecular-weight metabolites in the mouse model of ALD were observed and 48 specific biomarkers were identified. Geniposide was found to have a regulatory effect on 32 of them. Furthermore, targeted analysis of biomarkers showed clear separation between the model and geniposide treatment group. Fifteen biomarkers with high contribution to group differentiation were screened out. Also, a comprehensive analysis of a significant disturbance of multiple metabolic pathways indicated that geniposide could modify abnormal metabolism due to ethanol exposure, during which disorders relating to amino acid metabolism and the oxidative stress state could be alleviated. At the same time, accessory examinations, including plasma biochemical indicators and liver tissue pathological analysis, showed similar results. It was suggested that geniposide was effective as a hepatoprotective agent against ethanol-induced liver damage by re-balancing a wide range of metabolic disorders. PMID: 27896352 [PubMed - as supplied by publisher]

'Omics' and Plant Responses to Botrytis cinerea. Front Plant Sci. 2016;7:1658 Authors: AbuQamar SF, Moustafa K, Tran LP Abstract Botrytis cinerea is a dangerous plant pathogenic fungus with wide host ranges. This aggressive pathogen uses multiple weapons to invade and cause serious damages on its host plants. The continuing efforts of how to solve the "puzzle" of the multigenic nature of B. cinerea's pathogenesis and plant defense mechanisms against the disease caused by this mold, the integration of omic approaches, including genomics, transcriptomics, proteomics and metabolomics, along with functional analysis could be a potential solution. Omic studies will provide a foundation for development of genetic manipulation and breeding programs that will eventually lead to crop improvement and protection. In this mini-review, we will highlight the current progresses in research in plant stress responses to B. cinerea using high-throughput omic technologies. We also discuss the opportunities that omic technologies can provide to research on B. cinerea-plant interactions as an example showing the impacts of omics on agricultural research. PMID: 27895649 [PubMed - in process]

Glycoproteins and glycoproteomics in pancreatic cancer. World J Gastroenterol. 2016 Nov 14;22(42):9288-9299 Authors: Pan S, Brentnall TA, Chen R Abstract Aberrations in protein glycosylation and polysaccharides play a pivotal role in pancreatic tumorigenesis, influencing cancer progression, metastasis, immuno-response and chemoresistance. Abnormal expression in sugar moieties can impact the function of various glycoproteins, including mucins, surface receptors, adhesive proteins, proteoglycans, as well as their effectors and binding ligands, resulting in an increase in pancreatic cancer invasiveness and a cancer-favored microenvironment. Recent advance in glycoproteomics, glycomics and other chemical biology techniques have been employed to better understand the complex mechanism of glycosylation events and how they orchestrate molecular activities in genomics, proteomics and metabolomics implicated in pancreatic adenocarcinoma. A variety of strategies have been demonstrated targeting protein glycosylation and polysaccharides for diagnostic and therapeutic development. PMID: 27895417 [PubMed - in process]

UPLC-QTOF analysis reveals metabolomic changes in the flag leaf of wheat (Triticum aestivum L.) under low-nitrogen stress. Plant Physiol Biochem. 2016 Nov 18;111:30-38 Authors: Zhang Y, Ma XM, Wang XC, Liu JH, Huang BY, Guo XY, Xiong SP, La GX Abstract Wheat is one of the most important grain crop plants worldwide. Nitrogen (N) is an essential macronutrient for the growth and development of wheat and exerts a marked influence on its metabolites. To investigate the influence of low nitrogen stress on various metabolites of the flag leaf of wheat (Triticum aestivum L.), a metabolomic analysis of two wheat cultivars under different induced nitrogen levels was conducted during two important growth periods based on large-scale untargeted metabolomic analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF). Multivariate analyses-such as principle components analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA)-were used for data analysis. PCA yielded distinctive clustering information among the samples, classifying the wheat flag samples into two categories: those under normal N treatment and low N treatment. By processing OPLS-DA, eleven secondary metabolites were shown to be responsible for classifying the two groups. The secondary metabolites may be considered potential biomarkers of low nitrogen stress. Chemical analyses showed that most of the identified secondary metabolites were flavonoids and their related derivatives, such as iso-vitexin, iso-orientin and methylisoorientin-2″-O-rhamnoside, etc. This study confirmed the effect of low nitrogen stress on the metabolism of wheat, and revealed that the accumulation of secondary metabolites is a response to abiotic stresses. Meanwhile, we aimed to identify markers which could be used to monitor the nitrogen status of wheat crops, presumably to guide appropriate fertilization regimens. Furthermore, the UPLC-QTOF metabolic platform technology can be used to study metabolomic variations of wheat under abiotic stresses. PMID: 27894005 [PubMed - as supplied by publisher]

Resistance Training Improves Muscle Function and Cardiometabolic Risks But Not Quality of Life in Older People With Type 2 Diabetes Mellitus: A Randomized Controlled Trial. J Geriatr Phys Ther. 2016 Nov 23; Authors: Hsieh PL, Tseng CH, Tseng YJ, Yang WS Abstract BACKGROUND AND PURPOSE: In older people with type 2 diabetes mellitus (T2DM), the effects of aging and T2DM may compromise the function of skeletal muscle, deteriorate metabolic status, and jeopardize physical performance, aerobic capacity, and quality of life (QoL). The purpose of this study was to investigate the effects of 12 weeks of resistance training (RT) on muscle function, physical performance, cardiometabolic risks, and QoL in older people with T2DM. METHODS: This study was a randomized controlled trial that employed block randomization, assessor blinding, and the intention-to-treat principle. Thirty people 65 years or older with a diagnosis of T2DM were randomly assigned to either an exercise group or a control group and were further stratified by gender. The exercise group performed 8 RT exercises in 3 sets of 8 to 12 repetitions at 75% 1-repetition maximum (1-RM) 3 times per week for 12 weeks. The control group received usual care and maintained their daily activities and lifestyle. Muscle function (1-RM and muscle oxygenation responses), physical performance (5-repetition sit-to-stand test and Timed Up and Go test), cardiometabolic risks (aerobic capacity, blood pressure, body composition, glycemic control, lipids levels, and high-sensitivity C-reactive protein levels), and QoL (Audit of Diabetes-Dependent Quality of Life 19) were assessed at baseline (week 0) and after the 12-week interventions (week 12). RESULTS: The 1-RM chest-press and leg-press strength and physical performance in 5-repetition sit-to-stand test were significantly improved in the exercise group compared with the controls after the interventions. The exercise group had significantly lower resting systolic blood pressure (by -12.1 mm Hg, P = .036) than did the controls after 12 weeks of RT, without any significant within-group change in either group after intervention. The waist circumference, fasting glucose levels, and peak diastolic blood pressure tended to favor RT over usual care after the interventions. CONCLUSION: Twelve weeks of RT increased the maximal strength in chest-press and leg-press tests, and improved 5-repetition sit-to-stand performance in older people with T2DM. Our study demonstrated that supervised, structured RT was able to promote muscle function and alleviate cardiometabolic risks in people with T2DM 65 years or older. PMID: 27893563 [PubMed - as supplied by publisher]

A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2016 Nov 28;: Authors: Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L, Myridakis A, Delzenne NM, Klievink J, Bhattacharjee A, van der Ark KC, Aalvink S, Martinez LO, Dumas ME, Maiter D, Loumaye A, Hermans MP, Thissen JP, Belzer C, de Vos WM, Cani PD Abstract Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition. We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications. However, the underlying mechanisms of this protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine. We have addressed these issues here by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice. These improvements were notably associated with a modulation of the host urinary metabolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans. These findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders. PMID: 27892954 [PubMed - as supplied by publisher]

Metabolic response induced by parasitic plant-fungus interactions hinder amino sugar and nucleotide sugar metabolism in the host. Sci Rep. 2016 Nov 28;6:37434 Authors: Lee DK, Ahn S, Cho HY, Yun HY, Park JH, Lim J, Lee J, Kwon SW Abstract Infestation by the biotrophic pathogen Gymnosporangium asiaticum can be devastating for plant of the family Rosaceae. However, the phytopathology of this process has not been thoroughly elucidated. Using a metabolomics approach, we discovered the intrinsic activities that induce disease symptoms after fungal invasion in terms of microbe-induced metabolic responses. Through metabolic pathway enrichment and mapping, we found that the host altered its metabolite levels, resulting in accumulation of tetrose and pentose sugar alcohols, in response to this fungus. We then used a multiple linear regression model to evaluate the effect of the interaction between this abnormal accumulation of sugar alcohol and the group variable (control/parasitism). The results revealed that this accumulation resulted in deficiency in the supply of specific sugars, which led to a lack of amino sugar and nucleotide sugar metabolism. Halting this metabolism could hamper pivotal functions in the plant host, including cell wall synthesis and lesion repair. In conclusion, our findings indicate that altered metabolic responses that occur during fungal parasitism can cause deficiency in substrates in pivotal pathways and thereby trigger pathological symptoms. PMID: 27892480 [PubMed - in process]

Metabolic signatures of birthweight in 18 288 adolescents and adults. Int J Epidemiol. 2016 Oct;45(5):1539-1550 Authors: Würtz P, Wang Q, Niironen M, Tynkkynen T, Tiainen M, Drenos F, Kangas AJ, Soininen P, Skilton MR, Heikkilä K, Pouta A, Kähönen M, Lehtimäki T, Rose RJ, Kajantie E, Perola M, Kaprio J, Eriksson JG, Raitakari OT, Lawlor DA, Davey Smith G, Järvelin MR, Ala-Korpela M, Auro K Abstract BACKGROUND: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults. METHODS: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15-75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI). RESULTS: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R(2) = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood. CONCLUSIONS: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood. PMID: 27892411 [PubMed - in process]

Short-term NO2 exposure is associated with long-chain fatty acids in prospective cohorts from Augsburg, Germany: results from an analysis of 138 metabolites and three exposures. Int J Epidemiol. 2016 Oct;45(5):1528-1538 Authors: Ward-Caviness CK, Breitner S, Wolf K, Cyrys J, Kastenmüller G, Wang-Sattler R, Schneider A, Peters A Abstract BACKGROUND: Short-term exposure to air pollution is associated with morbidity and mortality. Metabolites are intermediaries in biochemical processes, and associations between air pollution and metabolites can yield unique mechanistic insights. METHODS: We used independent cross-sectional samples with targeted metabolomics (138 metabolites across five metabolite classes) from three cohort studies, each a part of the Cooperative Health Research in the Region of Augsburg (KORA). The KORA cohorts are numbered (1 to 4) according to which survey they belong to, and lettered S or F according to whether the survey was a baseline or follow-up survey. KORA F4 (N = 3044) served as our discovery cohort, with KORA S4 (N = 485) serving as the primary replication cohort. KORA F4 and KORA S4 were primarily fasting cohorts. We used the non-fasting KORA F3 (N = 377) cohort to evaluate replicated associations in non-fasting individuals, and we performed a random effects meta-analysis of all three cohorts. Associations between the 0-4-day lags and the 5-day average of particulate matter (PM)2.5, NO2 and ozone were modelled via generalized additive models. All air pollution exposures were scaled to the interquartile range, and effect estimates presented as percent changes relative to the geometric mean of the metabolite concentration (ΔGM). RESULTS: There were 10 discovery cohort associations, of which seven were lysophosphatidylcholines (LPCs); NO2 was the most ubiquitous exposure (5/10). The 5-day average NO2-LPC(28:0) association was associated at a Bonferroni corrected P-value threshold (P < 1.2x10(-4)) in KORA F4 [ΔGM = 11.5%; 95% confidence interval (CI) = 6.60, 16.3], and replicated (P < 0.05) in KORA S4 (ΔGM = 21.0%; CI = 4.56, 37.5). This association was not observed in the non-fasting KORA F3 cohort (ΔGM = -5.96%; CI = -26.3, 14.3), but remained in the random effects meta-analysis (ΔGM = 10.6%; CI = 0.16, 21). CONCLUSIONS: LPCs are associated with short-term exposure to air pollutants, in particular NO2 Further research is needed to understand the effect of nutritional/fasting status on these associations and the causal mechanisms linking air pollution exposure and metabolite profiles. PMID: 27892410 [PubMed - in process]

Metabolomics, nutrition and why epidemiology matters. Int J Epidemiol. 2016 Oct;45(5):1307-1310 Authors: Ebrahim S PMID: 27892407 [PubMed - in process]

Metabolomics-guided insights on bariatric surgery versus behavioral interventions for weight loss. Obesity (Silver Spring). 2016 Dec;24(12):2451-2466 Authors: Tulipani S, Griffin J, Palau-Rodriguez M, Mora-Cubillos X, Bernal-Lopez RM, Tinahones FJ, Corkey BE, Andres-Lacueva C Abstract OBJECTIVE: To review the metabolomic studies carried out so far to identify metabolic markers associated with surgical and dietary treatments for weight loss in subjects with obesity. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Thirty-two studies successfully met the eligibility criteria. The metabolic adaptations shared by surgical and dietary interventions mirrored a state of starvation ketoacidosis (increase of circulating ketone bodies), an increase of acylcarnitines and fatty acid β-oxidation, a decrease of specific amino acids including branched-chain amino acids (BCAA) and (lyso)glycerophospholipids previously associated with obesity, and adipose tissue expansion. The metabolic footprint of bariatric procedures was specifically characterized by an increase of bile acid circulating pools and a decrease of ceramide levels, a greater perioperative decline in BCAA, and the rise of circulating serine and glycine, mirroring glycemic control and inflammation improvement. In one study, 3-hydroxybutyrate was particularly identified as an early metabolic marker of long-term prognosis after surgery and proposed to increase current prognostic modalities and contribute to personalized treatment. CONCLUSIONS: Metabolomics helped in deciphering the metabolic response to weight loss treatments. Moving from association to causation is the next challenge to move to a further level of clinical application. PMID: 27891833 [PubMed - in process]

Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn. Br J Haematol. 2016 Nov 28;: Authors: Sonneveld ME, Koelewijn J, de Haas M, Admiraal J, Plomp R, Koeleman CA, Hipgrave Ederveen AL, Ligthart P, Wuhrer M, van der Schoot CE, Vidarsson G Abstract Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. HDFN is most often caused by anti-D but may also occur due to anti-K, -c- or -E. We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. IgG-Fc glycosylation of anti-RBC antibodies is shaped depending on the antigen. These features influence their clinical potency and may therefore be used to predict severity and identify those needing treatment. PMID: 27891581 [PubMed - as supplied by publisher]

Metabolic responses of Haliotis diversicolor to Vibrio parahaemolyticus infection. Fish Shellfish Immunol. 2016 Nov 24;: Authors: Lu J, Shi Y, Cai S, Feng J Abstract Vibrio parahemolyticus is a devastating bacterial pathogen that often causes outbreak of vibriosis in abalone Haliotis diversicolor. Elucidation of metabolic mechanisms of abalones in responding to V. parahemolyticus infection is essential for controlling the epidemic. In this work, (1)H NMR-based metabolomic techniques along with correlation and network analyses are used to investigate characteristic metabolites, as well as corresponding disturbed pathways in hepatopancreas and gill of H. diversicolor after V. parahemolyticus infection for 48 h. Results indicate that obvious gender- and tissue-specific metabolic responses are induced. Metabolic responses in female abalones are more clearly observed than those in males, which are primarily manifested in the accumulation of branched-chain amino acids and the depletion of organic osmolytes (homarine, betaine and taurine) in the infected gills of female abalones, as well as in the depletion of glutamate, branched-chain and aromatic amino acids in the infected hepatopancreases of female abalones. Moreover, based on major metabolic functions of the characteristic metabolites, we have found that V. parahemolyticus infection not only cause the disturbance in energy metabolism, nucleotide metabolism and osmotic balance, but also induce oxidative stress, immune stress and neurotoxic effect in different tissues with various mechanisms. Our study provides details of metabolic responses of abalones to V. parahemolyticus infection and will shed light on biochemical defence mechanisms of male and female hosts against pathogen infection. PMID: 27890800 [PubMed - as supplied by publisher]

The putative role of MALDI-MSI in the study of Membranous Nephropathy. Biochim Biophys Acta. 2016 Nov 23;: Authors: Smith A, L'Imperio V, Ajello E, Ferrario F, Mosele N, Stella M, Galli M, Chinello C, Pieruzzi F, Spasovski G, Pagni F, Magni F Abstract Membranous Nephropathy (MN) is an immunocomplex mediated renal disease that represents the leading cause of nephrotic syndrome in adults and is one of the most frequent glomerulopathies worldwide. This glomerular disease can manifest as primary (idiopathic) or secondary and this distinction is crucial when choosing the most appropriate management of patients. In secondary cases, the best strategy consists in treating the underlying disease whereas in primary forms, the possible identification of confirmatory markers of the idiopathic etiology underlining the process is requested by clinicians. Among those currently reported, the positivity to circulating antigens (PLA2R, IgG4 and THSD7A) was demonstrated in approximately 75% of iMN patients, while approximately 1 in 4 patients with iMN still lack a putative diagnostic marker. Ultimately, the discovery of useful biomarkers to help further stratify these two different forms of glomerulopathy seems mandatory. Here, MALDI-MSI was applied to formalin-fixed paraffin-embedded (FFPE) renal biopsies from histologically diagnosed primary and secondary MN patients (n=20) in order to evaluate the capability of this technology to detect alterations in their tissue proteome. MALDI-MSI was able to generate molecular signatures of primary and secondary MN, with one particular signal (m/z 1459), identified as Serine/threonine-protein kinase MRCK gamma, being over-expressed in the glomeruli of primary MN patients with respect to secondary MN. Furthermore, this proteomic approach detected a number of signals that could differentiate the different forms of iMN that were positive to PLA2R or IgG4 as well as a further set of signals (m/z 1094, 1116, 1381 and 1459) that distinguish these patients from those who were negative to both. These signals could potentially represent future targets to be investigated as proteomic markers for the further stratification of iMN patients. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. PMID: 27890680 [PubMed - as supplied by publisher]

Inhibition of autophagy with bafilomycin and chloroquine decreases mitochondrial quality and bioenergetic function in primary neurons. Redox Biol. 2016 Nov 18;11:73-81 Authors: Redmann M, Benavides GA, Berryhill TF, Wani WY, Ouyang X, Johnson MS, Ravi S, Barnes S, Darley-Usmar VM, Zhang J Abstract Autophagy is an important cell recycling program responsible for the clearance of damaged or long-lived proteins and organelles. Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that inhibit autophagy by targeting the lysosomes but through distinct mechanisms. Since it is now clear that mitochondrial quality control, particularly in neurons, is dependent on autophagy, it is important to determine whether these compounds modify cellular bioenergetics. To address this, we cultured primary rat cortical neurons from E18 embryos and used the Seahorse XF96 analyzer and a targeted metabolomics approach to measure the effects of bafilomycin A1 and chloroquine on bioenergetics and metabolism. We found that both bafilomycin and chloroquine could significantly increase the autophagosome marker LC3-II and inhibit key parameters of mitochondrial function, and increase mtDNA damage. Furthermore, we observed significant alterations in TCA cycle intermediates, particularly those downstream of citrate synthase and those linked to glutaminolysis. Taken together, these data demonstrate a significant impact of bafilomycin and chloroquine on cellular bioenergetics and metabolism consistent with decreased mitochondrial quality associated with inhibition of autophagy. PMID: 27889640 [PubMed - as supplied by publisher]

Early responses of mature Arabidopsis thaliana plants to reduced water potential in the agar-based polyethylene glycol infusion drought model. J Plant Physiol. 2016 Nov 10;208:70-83 Authors: Frolov A, Bilova T, Paudel G, Berger R, Balcke GU, Birkemeyer C, Wessjohann LA Abstract Drought is one of the most important environmental stressors resulting in increasing losses of crop plant productivity all over the world. Therefore, development of new approaches to increase the stress tolerance of crop plants is strongly desired. This requires precise and adequate modeling of drought stress. As this type of stress manifests itself as a steady decrease in the substrate water potential (ψw), agar plates infused with polyethylene glycol (PEG) are the perfect experimental tool: they are easy in preparation and provide a constantly reduced ψw, which is not possible in soil models. However, currently, this model is applicable only to seedlings and cannot be used for evaluation of stress responses in mature plants, which are obviously the most appropriate objects for drought tolerance research. To overcome this limitation, here we introduce a PEG-based agar infusion model suitable for 6-8-week-old A. thaliana plants, and characterize, to the best of our knowledge for the first time, the early drought stress responses of adult plants grown on PEG-infused agar. We describe essential alterations in the primary metabolome (sugars and related compounds, amino acids and polyamines) accompanied by qualitative and quantitative changes in protein patterns: up to 87 unique stress-related proteins were annotated under drought stress conditions, whereas further 84 proteins showed a change in abundance. The obtained proteome patterns differed slightly from those reported for seedlings and soil-based models. PMID: 27889524 [PubMed - as supplied by publisher]

Spectroscopic and E-tongue evaluation of medicinal plants: A taste of how rasa can be studied. J Ayurveda Integr Med. 2016 Nov 23;: Authors: Jayasundar R, Ghatak S Abstract BACKGROUND: The use of medicinal plants in Ayurveda is based on rasa, generally taken to represent taste as a sensory perception. This chemosensory parameter plays an important role in Ayurvedic pharmacology. OBJECTIVE: The aim is to explore the use of structuro-functional information deduced from analytical techniques for the rasa-based classification of medicinal plants in Ayurveda. MATERIALS AND METHODS: Methods of differential sensing and spectroscopic metabolomics have been used in select medicinal plants from three different taste categories (sweet, pungent and multiple taste): Tribulus terrestris, Vitis vinifera and Glycyrrhiza glabra from sweet category; Piper longum, Cuminum cyminum and Capsicum annum from pungent group; Emblica officinalis with five tastes. While Electronic tongue was used for evaluation of the sensorial property of taste, the chemical properties were studied with Nuclear Magnetic Resonance (NMR), Fourier Transform InfraRed (FTIR) and Laser Induced Breakdown Spectroscopy (LIBS). RESULTS: In terms of taste and phytochemical profiles, all samples were unique but with similarities within each group. While the sensor response in E-tongue showed similarities within the sweet and pungent categories, NMR spectra in the aromatic region showed close similarities between the plants in the sweet category. The sensory, phytochemical and phytoelemental profiles of E. officinalis (with five rasa) in particular, were unique. CONCLUSION: A combination of sensorial and chemical descriptors is a promising approach for a comprehensive evaluation and fingerprinting of the Ayurvedic pharmacological parameter rasa. PMID: 27889428 [PubMed - as supplied by publisher]

Andrée Gruslin award lecture: Metabolomics as an important modality to better understand preeclampsia. Placenta. 2016 Nov 16;: Authors: Benton SJ, Ly C, Vukovic S, Bainbridge SA Abstract Preeclampsia (PE) is a complex disorder that affects 3-5% of all pregnancies and is a leading cause of maternal and fetal morbidity and mortality. To date, the heterogeneity of clinical presentation, disease severity and outcomes have limited significant advances in early prediction, diagnosis, and therapeutic intervention of PE. The rapidly expanding field of metabolomics, which has the capacity to quantitatively detect low molecular weight compounds (metabolites) in tissue and biological fluids, shows tremendous promise in gaining a better understanding of PE. This review will discuss this emerging field and its contribution to recent advances in the understanding of PE pathophysiology, and identification of early predictive metabolic biomarkers for this complex disorder. PMID: 27889063 [PubMed - as supplied by publisher]