A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus

Ng, Daniel; Salim, Agus; Liu, Y.; Zou, Li; Xu, Fengguo; Huang, Shan; Leong, H.; Ong, Choon‐Nam

doi:10.1007/s00125-011-2339-6

Cited by 72 publications

(52 citation statements)

References 36 publications

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“…In contrast, LC/MS, which does not require the time-consuming derivatization procedure and is suitable for analysis of the phosphorylated compounds, has become a promising analytical approach due to its rapid, sensitive, and wide range analytical capability. In previous studies, it was found that an integrated use of GC/MS and LC/MS methods could provide a complementary and significantly improved analytical strategy with excellent stability and reproducibility [18,19,20]. …”

Section: Resultsmentioning

confidence: 99%

“…More recently, metabolomic technologies based on nuclear magnetic resonance (NMR), GC/MS, LC/MS have been well documented for application in various research fields [14,15,16,17]. In our previous studies, we have well established an integrated utilization of GC/MS and LC/MS approach to explore metabolic alterations in colorectal cancer and diabetes [18,19]. In the present study, owing to the difficulty of obtaining suitable clinical samples with confirmed diseases, we conducted an exploratory study using GC/MS- and LC/MS-based metabolomics in combination in order to study the profiles of metabolites among 17 patients with malignant and 15 benign SPNs, as well as 20 healthy controls.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Profiling of Plasma from Benign and Malignant Pulmonary Nodules Patients Using Mass Spectrometry-Based Metabolomics

Gao

Wen

et al. 2013

Metabolites

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Solitary pulmonary nodule (SPN or coin lesion) is a mass in the lung and can be commonly found in chest X-rays or computerized tomography (CT) scans. However, despite the advancement of imaging technologies, it is still difficult to distinguish malignant cancer from benign SPNs. Here we investigated the metabolic profiling of patients with benign and malignant pulmonary nodules. A combination of gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) was used to profile the plasma metabolites in 17 patients with malignant SPNs, 15 patients with benign SPNs and 20 healthy controls. The metabolic profiles were assayed using OPLS-DA, and further analyzed to identify marker metabolites related to diseases. Both GC/MS- and LC/MS-derived models showed clear discriminations in metabolic profiles among three groups. It was found that 63 metabolites (12 from GC/MS, 51 from LC/MS) contributed to the differences. Of these, 48 metabolites showed same change trend in both malignant and benign SPNs as compared with healthy controls, indicating some common pathways including inflammation and oxidative injury shared by two diseases. In contrast, 14 metabolites constituted distinct profiles that differentiated malignant from benign SPNs, which might be a unique biochemical feature associated with lung cancer. Overall, our data suggested that integration of two highly sensitive and complementary metabolomics platforms could enable a comprehensive metabolic profiling and assist in discrimination malignant from benign SPNs.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolic Profiling of Plasma from Benign and Malignant Pulmonary Nodules Patients Using Mass Spectrometry-Based Metabolomics

Gao

Wen

et al. 2013

Metabolites

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“…After centrifugation (4°C, 6000 rpm×1 min), the supernatant fraction was injected into GC-MS. The derivatised sample (1.0 µL) was introduced by splitless injection with an Agilent 7683 Series autosampler into an Agilent 6890 GC system equipped with a fused-silica capillary column HP-5MSI (30 m×0.25 mm i.d., 0.25 µm film thickness) as reported previously [21]. The inlet temperature was set at 250°C.…”

Section: Methodsmentioning

confidence: 99%

Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection

et al. 2013

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BackgroundDengue virus (DENV) is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF) is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis.Methodology/Principle FindingsSystems level characterization of serum metabolome and lipidome of adult DF patients at early febrile, defervescence, and convalescent stages of DENV infection was performed using liquid chromatography- and gas chromatography-mass spectrometry. The tractability of following metabolite and lipid changes in a relatively large sample size (n = 44) across three prominent infection stages allowed the identification of critical physiologic changes that coincided with the different stages. Sixty differential metabolites were identified in our metabolomics analysis and the main metabolite classes were free fatty acids, acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic pathways included fatty acid biosynthesis and β-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers.Conclusions/SignificanceDENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes, thus preventing the host from development of pathologies by excessive or prolonged inflammation. This study is the first example of how an omic- approach can divulge the extensive, concurrent, and dynamic host responses elicited by DENV and offers plausible physiological insights to why DF is self limiting.

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“…Area of each peak was normalized to that of internal standard FMOC-glycine in each data set. The missing values were replaced with a half of the minimum value found in the data set (Ng et al 2012). Ninety percent filtering was applied to the raw data to include only metabolites that were detectable in 90 % of the subjects in at least one of the treatment groups to ensure selection of relevant metabolites.…”

Section: Data Pre-processingmentioning

confidence: 99%

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

et al. 2014

Metabolomics

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The anti-malarial drug artesunate possesses anti-inflammatory and anti-oxidative actions in experimental asthma, comparable to corticosteroid. We hypothesized that artesunate may modulate disease-relevant metabolic alterations in allergic asthma. To explore metabolic profile changes induced by artesunate in allergic airway inflammation, we analysed bronchoalveolar lavage fluid (BALF) and serum from naïve and ovalbumininduced asthma mice treated with artesunate, using both gas and liquid chromatography-mass spectrometry metabolomics. Pharmacokinetics analyses of serum and lung tissues revealed that artesunate is rapidly converted into the active metabolite dihydroartemisinin. Artesunate effectively suppressed BALF total and differential counts, and repressed BALF Th2 cytokines, IL-17, IL-12(p40), MCP-1 and G-CSF levels. Artesunate had no effects on both BALF and serum metabolome in naïve mice. Artesunate promoted restoration of BALF sterols (cholesterol, cholic acid and cortol), phosphatidylcholines and carbohydrates (arabinose, mannose and galactose) and of serum 18-oxocortisol, galactose, glucose and glucouronic acid in asthma. Artesunate prevented OVA-induced increases in pro-inflammatory metabolites from arginine-proline metabolic pathway, particularly BALF levels of urea and alanine and serum levels of urea, proline, valine and homoserine. Multiple statistical correlation analyses revealed association between altered BALF and serum metabolites and inflammatory cytokines. Dexamethasone failed to reduce Wanxing Eugene Ho and Yong-Jiang Xu have contributed equally to this work.Electronic supplementary material The online version of this article (doi:10.1007/s11306-014-0699-x) contains supplementary material, which is available to authorized users. Metabolomics (2015) 11:380-390 DOI 10.1007 urea level and caused widespread changes in metabolites irrelevant to asthma development. Here we report the first metabolome profile of artesunate treatment in experimental asthma. Artesunate restored specific metabolic perturbations in airway inflammation, which correlated well with its anti-inflammatory actions. Our metabolomics findings further strengthen the therapeutic value of using artesunate to treat allergic asthma.

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A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus

Cited by 72 publications

References 36 publications

Metabolic Profiling of Plasma from Benign and Malignant Pulmonary Nodules Patients Using Mass Spectrometry-Based Metabolomics

Metabolic Profiling of Plasma from Benign and Malignant Pulmonary Nodules Patients Using Mass Spectrometry-Based Metabolomics

Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

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