Displaying publications 1 - 20 of 94 in total

  1. Ahmad SJ, Abdul Rahim MBH, Baharum SN, Baba MS, Zin NM
    J Trop Med, 2017;2017:2189814.
    PMID: 29123551 DOI: 10.1155/2017/2189814
    Natural products continue to play an important role as a source of biologically active substances for the development of new drug. Streptomyces, Gram-positive bacteria which are widely distributed in nature, are one of the most popular sources of natural antibiotics. Recently, by using a bioassay-guided fractionation, an antimalarial compound, Gancidin-W, has been discovered from these bacteria. However, this classical method in identifying potentially novel bioactive compounds from the natural products requires considerable effort and is a time-consuming process. Metabolomics is an emerging "omics" technology in systems biology study which integrated in process of discovering drug from natural products. Metabolomics approach in finding novel therapeutics agent for malaria offers dereplication step in screening phase to shorten the process. The highly sensitive instruments, such as Liquid Chromatography-Mass Spectrophotometry (LC-MS), Gas Chromatography-Mass Spectrophotometry (GC-MS), and Nuclear Magnetic Resonance ((1)H-NMR) spectroscopy, provide a wide range of information in the identification of potentially bioactive compounds. The current paper reviews concepts of metabolomics and its application in drug discovery of malaria treatment as well as assessing the antimalarial activity from natural products. Metabolomics approach in malaria drug discovery is still new and needs to be initiated, especially for drug research in Malaysia.
    Matched MeSH terms: Metabolomics
  2. Lawan A, Jesse FFA, Idris UH, Odhah MN, Arsalan M, Muhammad NA, et al.
    Microb. Pathog., 2018 Apr;117:175-183.
    PMID: 29471137 DOI: 10.1016/j.micpath.2018.02.039
    Innumerable Escherichia coli of animal origin are identified, which are of economic significance, likewise, cattle, sheep and goats are the carrier of enterohaemorrhagic E. coli, which are less pathogenic, and can spread to people by way of direct contact and through the contamination of foodstuff or portable drinking water, causing serious illness. The immunization of ruminants has been carried out for ages and is largely acknowledged as the most economical and maintainable process of monitoring E. coli infection in ruminants. Yet, only a limited number of E. coli vaccines are obtainable. Mucosal surfaces are the most important ingress for E. coli and thus mucosal immune responses function as the primary means of fortification. Largely contemporary vaccination processes are done by parenteral administration and merely limited number of E. coli vaccines are inoculated via mucosal itinerary, due to its decreased efficacy. Nevertheless, aiming at maximal mucosal partitions to stimulate defensive immunity at both mucosal compartments and systemic site epitomises a prodigious task. Enormous determinations are involved in order to improve on novel mucosal E. coli vaccines candidate by choosing apposite antigens with potent immunogenicity, manipulating novel mucosal itineraries of inoculation and choosing immune-inducing adjuvants. The target of E. coli mucosal vaccines is to stimulate a comprehensive, effective and defensive immunity by specifically counteracting the antibodies at mucosal linings and by the stimulation of cellular immunity. Furthermore, effective E. coli mucosal vaccine would make vaccination measures stress-free and appropriate for large number of inoculation. On account of contemporary advancement in proteomics, metagenomics, metabolomics and transcriptomics research, a comprehensive appraisal of the immeasurable genes and proteins that were divulged by a bacterium is now in easy reach. Moreover, there exist marvellous prospects in this bourgeoning technologies in comprehending the host bacteria affiliation. Accordingly, the flourishing knowledge could massively guarantee to the progression of immunogenic vaccines against E. coli infections in both humans and animals. This review highlight and expounds on the current prominence of mucosal and systemic immunogenic vaccines for the prevention of E. coli infections in ruminants.
    Matched MeSH terms: Metabolomics
  3. Eng-Chong T, Yean-Kee L, Chin-Fei C, Choon-Han H, Sher-Ming W, Li-Ping CT, et al.
    PMID: 23243448 DOI: 10.1155/2012/473637
    Boesenbergia rotunda is a herb from the Boesenbergia genera under the Zingiberaceae family. B. rotunda is widely found in Asian countries where it is commonly used as a food ingredient and in ethnomedicinal preparations. The popularity of its ethnomedicinal usage has drawn the attention of scientists worldwide to further investigate its medicinal properties. Advancement in drug design and discovery research has led to the development of synthetic drugs from B. rotunda metabolites via bioinformatics and medicinal chemistry studies. Furthermore, with the advent of genomics, transcriptomics, proteomics, and metabolomics, new insights on the biosynthetic pathways of B. rotunda metabolites can be elucidated, enabling researchers to predict the potential bioactive compounds responsible for the medicinal properties of the plant. The vast biological activities exhibited by the compounds obtained from B. rotunda warrant further investigation through studies such as drug discovery, polypharmacology, and drug delivery using nanotechnology.
    Matched MeSH terms: Metabolomics
  4. Rehman SU, Choe K, Yoo HH
    Molecules, 2016 Mar 10;21(3):331.
    PMID: 26978330 DOI: 10.3390/molecules21030331
    Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia. Decoctions of E. longifolia leaves are used for washing itches, while its fruits are used in curing dysentery. Its bark is mostly used as a vermifuge, while the taproots are used to treat high blood pressure, and the root bark is used for the treatment of diarrhea and fever. Mostly, the roots extract of E. longifolia are used as folk medicine for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress, syphilis and glandular swelling. The roots are also used as an aphrodisiac, antibiotic, appetite stimulant and health supplement. The plant is reported to be rich in various classes of bioactive compounds such as quassinoids, canthin-6-one alkaloids, β-carboline alkaloids, triterpene tirucallane type, squalene derivatives and biphenyl neolignan, eurycolactone, laurycolactone, and eurycomalactone, and bioactive steroids. Among these phytoconstituents, quassinoids account for a major portion of the E. longifolia root phytochemicals. An acute toxicity study has found that the oral Lethal Dose 50 (LD50) of the alcoholic extract of E. longifolia in mice is between 1500-2000 mg/kg, while the oral LD50 of the aqueous extract form is more than 3000 mg/kg. Liver and renal function tests showed no adverse changes at normal daily dose and chronic use of E. longifolia. Based on established literature on health benefits of E. longifolia, it is important to focus attention on its more active constituents and the constituents' identification, determination, further development and most importantly, the standardization. Besides the available data, more evidence is required regarding its therapeutic efficacy and safety, so it can be considered a rich herbal source of new drug candidates. It is very important to conserve this valuable medicinal plant for the health benefit of future generations.
    Matched MeSH terms: Metabolomics/methods
  5. Liew KL, Jee JM, Yap I, Yong PV
    PLoS ONE, 2016;11(4):e0153356.
    PMID: 27054608 DOI: 10.1371/journal.pone.0153356
    Cryptococcus neoformans is an encapsulated basidiomycetous yeast commonly associated with pigeon droppings and soil. The opportunistic pathogen infects humans through the respiratory system and the metabolic implications of C. neoformans infection have yet to be explored. Studying the metabolic profile associated with the infection could lead to the identification of important metabolites associated with pulmonary infection. Therefore, the aim of the study was to simulate cryptococcal infection at the primary site of infection, the lungs, and to identify the metabolic profile and important metabolites associated with the infection at low and high multiplicity of infections (MOI). The culture supernatant of lung epithelial cells infected with C. neoformans at MOI of 10 and 100 over a period of 18 hours were analysed using gas chromatography mass spectrometry. The metabolic profiles obtained were further analysed using multivariate analysis and the pathway analysis tool, MetaboAnalyst 2.0. Based on the results from the multivariate analyses, ten metabolites were selected as the discriminatory metabolites that were important in both the infection conditions. The pathways affected during early C. neoformans infection of lung epithelial cells were mainly the central carbon metabolism and biosynthesis of amino acids. Infection at a higher MOI led to a perturbance in the β-alanine metabolism and an increase in the secretion of pantothenic acid into the growth media. Pantothenic acid production during yeast infection has not been documented and the β-alanine metabolism as well as the pantothenate and CoA biosynthesis pathways may represent underlying metabolic pathways associated with disease progression. Our study suggested that β-alanine metabolism and the pantothenate and CoA biosynthesis pathways might be the important pathways associated with cryptococcal infection.
    Matched MeSH terms: Metabolomics*
  6. Shen G, Huang Y, Dong J, Wang X, Cheng KK, Feng J, et al.
    J. Agric. Food Chem., 2018 Jan 10;66(1):368-377.
    PMID: 29215281 DOI: 10.1021/acs.jafc.7b03182
    Taurine is indispensable in aquatic diets that are based solely on plant protein, and it promotes growth of many fish species. However, the physiological and metabolome effects of taurine on fish have not been well described. In this study, 1H NMR-based metabolomics approaches were applied to investigate the metabolite variations in Nile tilapia (Oreochromis nilotictus) muscle in order to visualize the metabolic trajectory and reveal the possible mechanisms of metabolic effects of dietary taurine supplementation on tilapia growth. After extraction using aqueous and organic solvents, 19 taurine-induced metabolic changes were evaluated in our study. The metabolic changes were characterized by differences in carbohydrate, amino acid, lipid, and nucleotide contents. The results indicate that taurine supplementation could significantly regulate the physiological state of fish and promote growth and development. These results provide a basis for understanding the mechanism of dietary taurine supplementation in fish feeding. 1H NMR spectroscopy, coupled with multivariate pattern recognition technologies, is an efficient and useful tool to map the fish metabolome and identify metabolic responses to different dietary nutrients in aquaculture.
    Matched MeSH terms: Metabolomics/methods*
  7. Yap, Ivan K.S.
    Metabonomics can be used to quantitatively measure dynamic biochemical responses of living organisms to physiological or pathological stimuli. A range of analytical tools such as high-resolution nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) combined with multivariate statistical analysis can be employed to create comprehensive metabolic signatures of biological samples including urine, plasma, faecal water and tissue extracts. These metabolic signatures can reflect the physiological or pathological condition of the organism and indicate imbalances in the homeostatic regulation of tissues and extracellular fluids. This technology has been employed in a diverse range of application areas including investigation of disease mechanisms, diagnosis/prognosis of pathologies, nutritional interventions and drug toxicity. Metabolic profiling is becoming increasingly important in identifying biomarkers of disease progression and drug intervention, and can provide additional information to support or aid the interpretation of genomic and proteomic data. With the new generation of postgenomic technologies, the paradigm in many biological fields has shifted to either top down systems biology approaches, aiming to achieve a general understanding of the global and integrated response of an organism or to bottom up modelling of specific pathways and networks using a priori knowledge based on mining large bodies of literature. Whilst metabolic profiling lends itself to either approach, using it in an exploratory and hypothesis generating capacity clearly allows new mechanisms to be uncovered.
    Matched MeSH terms: Metabolomics
  8. Abu Bakar MH, Sarmidi MR, Cheng KK, Ali Khan A, Suan CL, Zaman Huri H, et al.
    Mol Biosyst, 2015 Jul;11(7):1742-74.
    PMID: 25919044 DOI: 10.1039/c5mb00158g
    Metabolomic studies on obesity and type 2 diabetes mellitus have led to a number of mechanistic insights into biomarker discovery and comprehension of disease progression at metabolic levels. This article reviews a series of metabolomic studies carried out in previous and recent years on obesity and type 2 diabetes, which have shown potential metabolic biomarkers for further evaluation of the diseases. Literature including journals and books from Web of Science, Pubmed and related databases reporting on the metabolomics in these particular disorders are reviewed. We herein discuss the potential of reported metabolic biomarkers for a novel understanding of disease processes. These biomarkers include fatty acids, TCA cycle intermediates, carbohydrates, amino acids, choline and bile acids. The biological activities and aetiological pathways of metabolites of interest in driving these intricate processes are explained. The data from various publications supported metabolomics as an effective strategy in the identification of novel biomarkers for obesity and type 2 diabetes. Accelerating interest in the perspective of metabolomics to complement other fields in systems biology towards the in-depth understanding of the molecular mechanisms underlying the diseases is also well appreciated. In conclusion, metabolomics can be used as one of the alternative approaches in biomarker discovery and the novel understanding of pathophysiological mechanisms in obesity and type 2 diabetes. It can be foreseen that there will be an increasing research interest to combine metabolomics with other omics platforms towards the establishment of detailed mechanistic evidence associated with the disease processes.
    Matched MeSH terms: Metabolomics
  9. Afzan A, Kasim N, Ismail NH, Azmi N, Ali AM, Mat N, et al.
    Metabolomics, 2019 Mar 04;15(3):35.
    PMID: 30830457 DOI: 10.1007/s11306-019-1489-2
    BACKGROUND: Ficus deltoidea Jack (Moraceae) is a plant used in Malaysia for various diseases including as a supplement in diabetes management. Morphology distinction of the 7 main varieties (var. angustifolia, var. bilobata, var. deltoidea, var. intermedia, var. kunstleri, var. motleyana and var. trengganuensis) is challenging due to the extreme leaf heterophylly and unclear varietal boundaries, making it difficult for quality control of F. deltoidea products.

    OBJECTIVE: We aimed to compare the phytochemical composition of 7 varieties growing in different conditions at various geographical locations. We also aimed to establish the quality control markers for the authentication of these varieties.

    METHODS: We applied untargeted UHPLC-TOFMS metabolomics to discriminate 100 leaf samples of F. deltoidea collected from 6 locations in Malaysia. A genetic analysis on 21 leaf samples was also performed to validate the chemotaxonomy differentiation.

    RESULTS: The PCA and HCA analysis revealed the existence of 3 chemotypes based on the differentiation in the flavonoid content. The PLS-DA analysis identified 15 glycosylated flavone markers together with 1 furanocoumarin. These markers were always consistent for the respective varieties, regardless of the geographical locations and growing conditions. The chemotaxonomy differentiation was in agreement with the DNA sequencing. In particular, var. bilobata accession which showed divergent morphology was also differentiated by the chemical fingerprints and genotype.

    CONCLUSION: Chemotype differentiation based on the flavonoid fingerprints along with the proposed markers provide a powerful identification tool to complement morphology and genetic analyses for the quality control of raw materials and products from F. deltoidea.

    Matched MeSH terms: Metabolomics
  10. Au A, Cheng KK, Wei LK
    Adv. Exp. Med. Biol., 2017;956:599-613.
    PMID: 27722964 DOI: 10.1007/5584_2016_79
    Hypertension is a common but complex human disease, which can lead to a heart attack, stroke, kidney disease or other complications. Since the pathogenesis of hypertension is heterogeneous and multifactorial, it is crucial to establish a comprehensive metabolomic approach to elucidate the molecular mechanism of hypertension. Although there have been limited metabolomic, lipidomic and pharmacometabolomic studies investigating this disease to date, metabolomic studies on hypertension have provided greater insights into the identification of disease-specific biomarkers, predicting treatment outcome and monitor drug safety and efficacy. Therefore, we discuss recent updates on the applications of metabolomics technology in human hypertension with a focus on metabolic biomarker discovery.
    Matched MeSH terms: Metabolomics/methods*
  11. Fan X, Matsumoto H, Wang Y, Hu Y, Liu Y, Fang H, et al.
    Environ. Sci. Technol., 2019 Nov 19;53(22):13042-13052.
    PMID: 31631659 DOI: 10.1021/acs.est.9b04616
    Rice fungal pathogens, responsible for severe rice yield loss and biotoxin contamination, cause increasing concerns on environmental safety and public health. In the paddy environment, we observed that the asymptomatic rice phyllosphere microenvironment was dominated by an indigenous fungus, Aspergillus cvjetkovicii, which positively correlated with alleviated incidence of Magnaporthe oryzae, one of the most aggressive plant pathogens. Through the comparative metabolic profiling for the rice phyllosphere microenvironment, two metabolites were assigned as exclusively enriched metabolic markers in the asymptomatic phyllosphere and increased remarkably in a population-dependent manner with A. cvjetkovicii. These two metabolites evidenced to be produced by A. cvjetkovicii in either a phyllosphere microenvironment or artificial media were purified and identified as 2(3H)-benzofuranone and azulene, respectively, by gas chromatography coupled to triple quadrupole mass spectrometry and nuclear magnetic resonance analyses. Combining with bioassay analysis in vivo and in vitro, we found that 2(3H)-benzofuranone and azulene exerted dissimilar actions at the stage of infection-related development of M. oryzae. A. cvjetkovicii produced 2(3H)-benzofuranone at the early stage to suppress MoPer1 gene expression, leading to inhibited mycelial growth, while azulene produced lately was involved in blocking of appressorium formation by downregulation of MgRac1. More profoundly, the microenvironmental interplay dominated by A. cvjetkovicii significantly blocked M. oryzae epidemics in the paddy environment from 54.7 to 68.5% (p < 0.05). Our study first demonstrated implication of the microenvironmental interplay dominated by indigenous and beneficial fungus to ecological balance and safety of the paddy environment.
    Matched MeSH terms: Metabolomics
  12. Saiman MZ, Mustafa NR, Verpoorte R
    Methods Mol. Biol., 2018;1815:437-455.
    PMID: 29981141 DOI: 10.1007/978-1-4939-8594-4_31
    The plant Catharanthus roseus is a rich source of terpenoid indole alkaloids (TIA). Some of the TIA are important as antihypertensive (ajmalicine) and anticancer (vinblastine and vincristine) drugs. However, production of the latter is very low in the plant. Therefore, in vitro plant cell cultures have been considered as a potential supply of these chemicals or their precursors. Some monomeric alkaloids can be produced by plant cell cultures, but not on a level feasible for commercialization, despite extensive studies on this plant that deepened the understanding of the TIA biosynthesis and its regulation. In order to analyze the metabolites in C. roseus cell cultures, this chapter presents the method of TIA, carotenoids, and phytosterols analyses. Furthermore, an NMR-based metabolomics approach to study C. roseus cell culture is described.
    Matched MeSH terms: Metabolomics/methods*
  13. Munirah Md Noh S, Hamimah Sheikh Abdul Kadir S, Vasudevan S
    Biomolecules, 2019 06 22;9(6).
    PMID: 31234474 DOI: 10.3390/biom9060243
    The anti-fibrotic properties of ranibizumab have been well documented. As an antagonist to vascular endothelial growth factor (VEGF), ranibizumab works by binding and neutralizing all active VEGF-A, thus limiting progressive cell growth and proliferation. Ranibizumab application in ocular diseases has shown remarkable desired effects; however, to date, its antifibrotic mechanism is not well understood. In this study, we identified metabolic changes in ranibizumab-treated human Tenon's fibroblasts (HTFs). Cultured HTFs were treated for 48 h with 0.5 mg/mL of ranibizumab and 0.5 mg/mL control IgG antibody which serves as a negative control. Samples from each group were injected into Agilent 6520 Q-TOF liquid chromatography/mass spectrometer (LC/MS) system to establish the metabolite expression in both ranibizumab treated cells and control group. Data obtained was analyzed using Agilent Mass Hunter Qualitative Analysis software to identify the most regulated metabolite following ranibizumab treatment. At p-value < 0.01 with the cut off value of two-fold change, 31 identified metabolites were found to be significantly upregulated in ranibizumab-treated group, with six of the mostly upregulated having insignificant role in fibroblast cell cycle and wound healing regulations. Meanwhile, 121 identified metabolites that were downregulated, and seven of the mostly downregulated are significantly involved in cell cycle and proliferation. Our findings suggest that ranibizumab abrogates the tissue scarring and wound healing process by regulating the expression of metabolites associated with fibrotic activity. In particular, we found that vitamin Bs are important in maintaining normal folate cycle, nucleotide synthesis, and homocysteine and spermidine metabolism. This study provides an insight into ranibizumab's mechanism of action in HTFs from the perspective of metabolomics.
    Matched MeSH terms: Metabolomics*
  14. Loke MF, Chua EG, Gan HM, Thulasi K, Wanyiri JW, Thevambiga I, et al.
    PLoS ONE, 2018;13(12):e0208584.
    PMID: 30576312 DOI: 10.1371/journal.pone.0208584
    Colorectal cancer (CRC) is ranked the third most common cancer in human worldwide. However, the exact mechanisms of CRC are not well established. Furthermore, there may be differences between mechanisms of CRC in the Asian and in the Western populations. In the present study, we utilized a liquid chromatography-mass spectrometry (LC-MS) metabolomic approach supported by the 16S rRNA next-generation sequencing to investigate the functional and taxonomical differences between paired tumor and unaffected (normal) surgical biopsy tissues from 17 Malaysian patients. Metabolomic differences associated with steroid biosynthesis, terpenoid biosynthesis and bile metabolism could be attributed to microbiome differences between normal and tumor sites. The relative abundances of Anaerotruncus, Intestinimonas and Oscillibacter displayed significant relationships with both steroid biosynthesis and terpenoid and triterpenoid biosynthesis pathways. Metabolites involved in serotonergic synapse/ tryptophan metabolism (Serotonin and 5-Hydroxy-3-indoleacetic acid [5-HIAA]) were only detected in normal tissue samples. On the other hand, S-Adenosyl-L-homocysteine (SAH), a metabolite involves in methionine metabolism and methylation, was frequently increased in tumor relative to normal tissues. In conclusion, this study suggests that local microbiome dysbiosis may contribute to functional changes at the cancer sites. Results from the current study also contributed to the list of metabolites that are found to differ between normal and tumor sites in CRC and supported our quest for understanding the mechanisms of carcinogenesis.
    Matched MeSH terms: Metabolomics*
  15. Abdul-Hamid NA, Abas F, Maulidiani M, Ismail IS, Tham CL, Swarup S, et al.
    Anal. Biochem., 2019 07 01;576:20-32.
    PMID: 30970239 DOI: 10.1016/j.ab.2019.04.001
    The variation in the extracellular metabolites of RAW 264.7 cells obtained from different passage numbers (passage 9, 12 and 14) was examined. The impact of different harvesting protocols (trypsinization and scraping) on recovery of intracellular metabolites was then assessed. The similarity and variation in the cell metabolome was investigated using 1H NMR metabolic profiling modeled using multivariate data analysis. The characterization and quantification of metabolites was performed to determine the passage-related and harvesting-dependent effects on impacted metabolic networks. The trypsinized RAW cells from lower passages gave higher intensities of most identified metabolites, including asparagine, serine and tryptophan. Principal component analysis revealed variation between cells from different passages and harvesting methods, as indicated by the formation of clusters in score plot. Analysis of S-plots revealed metabolites that acted as biomarkers in discriminating cells from different passages including acetate, serine, lactate and choline. Meanwhile lactate, glutamine and pyruvate served as biomarkers for differentiating trypsinized and scraped cells. In passage-dependent effects, glycolysis and TCA cycle were influential, whereas glycerophospholipid metabolism was affected by the harvesting method. Overall, it is proposed that typsinized RAW cells from lower passage numbers are more appropriate when conducting experiments related to NMR metabolomics.
    Matched MeSH terms: Metabolomics/methods*
  16. Schmidt JA, Fensom GK, Rinaldi S, Scalbert A, Appleby PN, Achaintre D, et al.
    Int. J. Cancer, 2020 02 01;146(3):720-730.
    PMID: 30951192 DOI: 10.1002/ijc.32314
    Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD  = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD  = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR1SD  = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD  = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.
    Matched MeSH terms: Metabolomics
  17. Durani LW, Hamezah HS, Ibrahim NF, Yanagisawa D, Nasaruddin ML, Mori M, et al.
    J. Alzheimers Dis., 2018;64(1):249-267.
    PMID: 29889072 DOI: 10.3233/JAD-170880
    We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.
    Matched MeSH terms: Metabolomics/methods
  18. Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Bellier JP, et al.
    Exp. Gerontol., 2018 Oct 01;111:53-64.
    PMID: 29981398 DOI: 10.1016/j.exger.2018.07.002
    Decrease in multiple functions occurs in the brain with aging, all of which can contribute to age-related cognitive and locomotor impairments. Brain atrophy specifically in hippocampus, medial prefrontal cortex (mPFC), and striatum, can contribute to this age-associated decline in function. Our recent metabolomics analysis showed age-related changes in these brain regions. To further understand the aging processes, analysis using a proteomics approach was carried out. This study was conducted to identify proteome profiles in the hippocampus, mPFC, and striatum of 14-, 18-, 23-, and 27-month-old rats. Proteomics analysis using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins in the striatum. Of these proteins, 97 in the hippocampus, 25 in mPFC, and 5 in striatum were differentially expressed with age. The altered proteins were classified into three ontologies (cellular component, molecular function, and biological process) containing 44, 38, and 35 functional groups in the hippocampus, mPFC, and striatum, respectively. Most of these altered proteins participate in oxidative phosphorylation (e.g. cytochrome c oxidase and ATP synthase), glutathione metabolism (e.g. peroxiredoxins), or calcium signaling pathway (e.g. protein S100B and calmodulin). The most prominent changes were observed in the oldest animals. These results suggest that alterations in oxidative phosphorylation, glutathione metabolism, and calcium signaling pathway are involved in cognitive and locomotor impairments in aging.
    Matched MeSH terms: Metabolomics
  19. Low CF, Rozaini MZH, Musa N, Syarul Nataqain B
    J. Fish Dis., 2017 Oct;40(10):1267-1277.
    PMID: 28252175 DOI: 10.1111/jfd.12610
    The approaches of transcriptomic and proteomic have been widely used to study host-pathogen interactions in fish diseases, and this is comparable to the recently emerging application of metabolomic in elucidating disease-resistant mechanisms in fish that gives new insight into potential therapeutic strategies to improve fish health. Metabolomic is defined as the large-scale study of all metabolites within an organism and represents the frontline in the 'omics' approaches, providing direct information on the metabolic responses and perturbations in metabolic pathways. In this review, the current research in infectious fish diseases using metabolomic approach will be summarized. The metabolomic approach in economically important fish infected with viruses, bacteria and nematodes will also be discussed. The potential of the metabolomic approach for management of these infectious diseases as well as the challenges and the limitations of metabolomic in fish disease studies will be explored. Current review highlights the impacts of metabolomic studies in infectious fish diseases, which proposed the potential of new therapeutic strategies to enhance disease resistance in fish.
    Matched MeSH terms: Metabolomics/instrumentation; Metabolomics/methods*
  20. Pariyani R, Ismail IS, Ahmad Azam A, Abas F, Shaari K
    J. Sci. Food Agric., 2017 Sep;97(12):4169-4179.
    PMID: 28233369 DOI: 10.1002/jsfa.8288
    BACKGROUND: Java tea is a well-known herbal infusion prepared from the leaves of Orthosiphon stamineus (OS). The biological properties of tea are in direct correlation with the primary and secondary metabolite composition, which in turn largely depends on the choice of drying method. Herein, the impact of three commonly used drying methods, i.e. shade, microwave and freeze drying, on the metabolite composition and antioxidant activity of OS leaves was investigated using proton nuclear magnetic resonance (1 H NMR) spectroscopy combined with multivariate classification and regression analysis tools.

    RESULTS: A total of 31 constituents comprising primary and secondary metabolites belonging to the chemical classes of fatty acids, amino acids, sugars, terpenoids and phenolic compounds were identified. Shade-dried leaves were identified to possess the highest concentrations of bioactive secondary metabolites such as chlorogenic acid, caffeic acid, luteolin, orthosiphol and apigenin, followed by microwave-dried samples. Freeze-dried leaves had higher concentrations of choline, amino acids leucine, alanine and glutamine and sugars such as fructose and α-glucose, but contained the lowest levels of secondary metabolites.

    CONCLUSION: Metabolite profiling coupled with multivariate analysis identified shade drying as the best method to prepare OS leaves as Java tea or to include in traditional medicine preparation. © 2017 Society of Chemical Industry.

    Matched MeSH terms: Metabolomics
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