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Article ; Online: Metabolomic Signature of Diabetic Kidney Disease in Cerebrospinal Fluid and Plasma of Patients with Type 2 Diabetes Using Liquid Chromatography-Mass Spectrometry

Huan-Tang Lin / Mei-Ling Cheng / Chi-Jen Lo / Gigin Lin / Fu-Chao Liu

Diagnostics, Vol 12, Iss 2626, p

2022 Volume 2626

Abstract: Diabetic kidney disease (DKD) is the major cause of end stage renal disease in patients with type 2 diabetes mellitus (T2DM). The subtle metabolic changes in plasma and cerebrospinal fluid (CSF) might precede the development of DKD by years. In this ... ...

Abstract	Diabetic kidney disease (DKD) is the major cause of end stage renal disease in patients with type 2 diabetes mellitus (T2DM). The subtle metabolic changes in plasma and cerebrospinal fluid (CSF) might precede the development of DKD by years. In this longitudinal study, CSF and plasma samples were collected from 28 patients with T2DM and 25 controls, during spinal anesthesia for elective surgery in 2017. These samples were analyzed using liquid chromatography-mass spectrometry (LC-MS) in 2017, and the results were correlated with current DKD in 2017, and the development of new-onset DKD, in 2021. Comparing patients with T2DM having new-onset DKD with those without DKD, revealed significantly increased CSF tryptophan and plasma uric acid levels, whereas phosphatidylcholine 36:4 was lower. The altered metabolites in the current DKD cases were uric acid and paraxanthine in the CSF and uric acid, L-acetylcarnitine, bilirubin, and phosphatidylethanolamine 38:4 in the plasma. These metabolic alterations suggest the defective mitochondrial fatty acid oxidation and purine and phospholipid metabolism in patients with DKD. A correlation analysis found CSF uric acid had an independent positive association with the urine albumin-to-creatinine ratio. In conclusion, these identified CSF and plasma biomarkers of DKD in diabetic patients, might be valuable for monitoring the DKD progression.
Keywords	diabetes mellitus ; cerebrospinal fluid ; metabolomics ; diabetic kidney disease ; mass spectrometry ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Alternations of Lipoprotein Profiles in the Plasma as Biomarkers of Huntington’s Disease

Kuo-Hsuan Chang / Mei-Ling Cheng / Chi-Jen Lo / Chun-Ming Fan / Yih-Ru Wu / Chiung-Mei Chen

Cells, Vol 12, Iss 385, p

2023 Volume 385

Abstract: Alterations in lipid composition and disturbed lipoprotein metabolism are involved in the pathomechanism of Huntington’s disease (HD). Here, we measured 112 lipoprotein subfractions and components in the plasma of 20 normal controls, 24 symptomatic ( ... ...

Abstract	Alterations in lipid composition and disturbed lipoprotein metabolism are involved in the pathomechanism of Huntington’s disease (HD). Here, we measured 112 lipoprotein subfractions and components in the plasma of 20 normal controls, 24 symptomatic (sympHD) and 9 presymptomatic (preHD) HD patients. Significant changes were found in 30 lipoprotein subfractions and components in all HD patients. Plasma levels of total cholesterol (CH), apolipoprotein (Apo)B, ApoB-particle number (PN), and components of low-density lipoprotein (LDL) were lower in preHD and sympHD patients. Components of LDL4, LDL5, LDL6 and high-density lipoprotein (HDL)4 demonstrated lower levels in preHD and sympHD patients compared with controls. Components in LDL3 displayed lower levels in sympHD compared with the controls, whereas components in very low-density lipoprotein (VLDL)5 were higher in sympHD patients compared to the controls. The levels of components in HDL4 and VLDL5 demonstrated correlation with the scores of motor assessment, independence scale or functional capacity of Unified Huntington’s Disease Rating Scale. These findings indicate the potential of components of VLDL5, LDL3, LDL4, LDL5 and HDL4 to serve as the biomarkers for HD diagnosis and disease progression, and demonstrate substantial evidence of the involvement of lipids and apolipoproteins in HD pathogenesis.
Keywords	Huntington’s disease ; biomarker ; lipoprotein ; high-density lipoprotein ; low-density lipoprotein ; very low-density lipoprotein ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Alterations of Sphingolipid and Phospholipid Pathways and Ornithine Level in the Plasma as Biomarkers of Parkinson’s Disease

Kuo-Hsuan Chang / Mei-Ling Cheng / Hsiang-Yu Tang / Cheng-Yu Huang / Hsiu-Chuan Wu / Chiung-Mei Chen

Cells, Vol 11, Iss 395, p

2022 Volume 395

Abstract: The biomarkers of Parkinson’s disease (PD) remain to be investigated. This work aimed to identify blood biomarkers for PD using targeted metabolomics analysis. We quantified the plasma levels of 255 metabolites in 92 PD patients and 60 healthy controls ( ... ...

Abstract	The biomarkers of Parkinson’s disease (PD) remain to be investigated. This work aimed to identify blood biomarkers for PD using targeted metabolomics analysis. We quantified the plasma levels of 255 metabolites in 92 PD patients and 60 healthy controls (HC). PD patients were sub-grouped into early (Hoehn–Yahr stage ≤ 2, n = 72) and advanced (Hoehn–Yahr stage > 2, n = 20) stages. Fifty-nine phospholipids, 3 fatty acids, 3 amino acids, and 7 biogenic amines, demonstrated significant alterations in PD patients. Six of them, dihydro sphingomyelin (SM) 24:0, 22:0, 20:0, phosphatidylethanolamine-plasmalogen (PEp) 38:6, and phosphatidylcholine 38:5 and 36:6, demonstrated lowest levels in PD patients in the advanced stage, followed by those in the early stage and HC. By contrast, the level of ornithine was highest in PD patients at the advanced stage, followed by those at the early stage and HC. These biomarker candidates demonstrated significant correlations with scores of motor disability, cognitive dysfunction, depression, and quality of daily life. The support vector machine algorithm using α-synuclein, dihydro SM 24:0, and PEp 38:6 demonstrated good ability to separate PD from HC (AUC: 0.820). This metabolomic analysis demonstrates new plasma biomarker candidates for PD and supports their role in participating PD pathogenesis and monitoring disease progression.
Keywords	Parkinson’s disease ; biomarker ; metabolomics ; sphingomyelin ; phosphatidylethanolamine ; phosphatidylcholine ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Amino Acid-Based Metabolic Panel Provides Robust Prognostic Value Additive to B-Natriuretic Peptide and Traditional Risk Factors in Heart Failure

Chao-Hung Wang / Mei-Ling Cheng / Min-Hui Liu

Disease Markers, Vol

2018 Volume 2018

Abstract: Metabolic disturbances represent functional perturbation in peripheral tissues and predict outcomes in patients with heart failure (HF). This study developed an amino acid-based metabolic panel and sought to see whether this panel could add diagnostic ... ...

Abstract	Metabolic disturbances represent functional perturbation in peripheral tissues and predict outcomes in patients with heart failure (HF). This study developed an amino acid-based metabolic panel and sought to see whether this panel could add diagnostic and prognostic value to currently used B-type natriuretic peptide (BNP) measurements. Mass spectrometry and ultra-performance liquid chromatography were performed on 1288 participants, including 129 normal controls and 712 patients at HF stages A to D in the initial cohort and 447 stage C patients in the validation cohort. Patients were followed up for composite events (death/HF-related rehospitalization). Histidine, ornithine, and phenylalanine were 3 metabolites found strongly significant to identify patients at stage C and were adopted to develop the HOP panel. Compared to BNP, HOP had better value in discriminating the patients at different stages, especially in elderly patients and those with atrial fibrillation, high body mass index, or kidney dysfunction. HOP was correlated with the distance of 6 min walking distance better than BNP. For prognosis, HOP predicted composite events in patients at stages C and D, independent of log (BNP), age, sex, left ventricular ejection fraction, New York Heart Association functional class, HF stage, diabetes mellitus, chronic kidney disease, hypertension, hemoglobin, and albumin. Higher BNP (≥750 pg/mL) along with higher HOP (≥14) robustly predicted lower event-free survival compared to all others [hazard ratio=3.15 (2.23–4.46), p<0.001]. The prognostic value of HOP was confirmed in the validation cohort. In conclusion, aiming for clinical applications, this study proved that the HOP panel provides diagnostic and prognostic value additive to BNP and traditional risk factors.
Keywords	Medicine (General) ; R5-920
Subject code	610 ; 616
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Integrated metabolic and microbial analysis reveals host–microbial interactions in IgE-mediated childhood asthma

Chih-Yung Chiu / Mei-Ling Cheng / Meng-Han Chiang / Chia-Jung Wang / Ming-Han Tsai / Gigin Lin

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 7

Abstract: Abstract A metabolomics-based approach to address the molecular mechanism of childhood asthma with immunoglobulin E (IgE) or allergen sensitization related to microbiome in the airways remains lacking. Fifty-three children with lowly sensitized non- ... ...

Abstract	Abstract A metabolomics-based approach to address the molecular mechanism of childhood asthma with immunoglobulin E (IgE) or allergen sensitization related to microbiome in the airways remains lacking. Fifty-three children with lowly sensitized non-atopic asthma (n = 15), highly sensitized atopic asthma (n = 13), and healthy controls (n = 25) were enrolled. Blood metabolomic analysis with 1H-nuclear magnetic resonance (NMR) spectroscopy and airway microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen-specific IgE levels for lowly and highly sensitized asthma was also assessed. Four metabolites including tyrosine, isovalerate, glycine, and histidine were uniquely associated with lowly sensitized asthma, whereas one metabolite, acetic acid, was strongly associated with highly sensitized asthma. Metabolites associated with highly sensitized asthma (valine, isobutyric acid, and acetic acid) and lowly sensitized asthma (isovalerate, tyrosine, and histidine) were strongly correlated each other (P < 0.01). Highly sensitized asthma associated metabolites were mainly enriched in pyruvate and acetyl-CoA metabolisms. Metabolites associated with highly sensitized atopic asthma were mostly correlated with microbiota in the airways. Acetic acid, a short-chain fatty acid (SCFA), was negatively correlated with the genus Atopobium (P < 0.01), but positively correlated with the genus Fusobacterium (P < 0.05). In conclusion, metabolomics reveals microbes-related metabolic pathways associated with IgE responses to house dust mite allergens in childhood asthma. A strong correlation of metabolites related to highly sensitized atopic asthma with airway microbiota provides linkages between the host–microbial interactions and asthma endotypes.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Profiling of Serum Metabolites of Acute Intermittent Porphyria and Asymptomatic HMBS Mutation Carriers

Chia-Ni Lin / Ming-Shi Shiao / Mei-Ling Cheng / Chiung-Mei Chen / Hung-Chou Kuo

Cells, Vol 10, Iss 2579, p

2021 Volume 2579

Abstract: This study aims to present the serum metabolite profiles of patients with acute intermittent porphyria (AIP) and identify specific metabolites that could potentially discriminate between AIP, asymptomatic HMBS mutation carriers, and healthy individuals. ... ...

Abstract	This study aims to present the serum metabolite profiles of patients with acute intermittent porphyria (AIP) and identify specific metabolites that could potentially discriminate between AIP, asymptomatic HMBS mutation carriers, and healthy individuals. The study cohort included 46 female participants: 21 AIP patients, 5 asymptomatic carriers, and 20 ‘normal’ participants (without HMBS gene mutation). Serum samples were analyzed for 157 selected metabolites or clinical variables using an assay combining liquid chromatography MS/MS and direct flow injection. AUC analysis was used to distinguish unique variables between the three groups. A total of 15 variables differed significantly between the AIP and normal control group (VIP score > 1.0 and p < 0.05 with FDR correction). In AIP patients, the levels tyrosine, valine, and eGFR were significantly lower, and the levels of sphingomyelin C16:0, C24:0, C24:1, phosphatidylcholine diacyl C32:1, C36:1, C36:3, ornithine, sarcosine, citrulline, blood urea nitrogen AST, and ALT were significantly higher. The AUC of these 15 variables in discriminating between normal and AIP patients ranged between 0.73 and 0.94 ( p < 0.05). In conclusion, serum metabolic profiles differ between normal individuals and patients carrying the HMBS mutation. The unique metabolites associated with AIP identified in this study may be useful for monitoring the development of AIP symptoms.
Keywords	porphobilinogen deaminase ; metabolomic profiling ; metabolic reprogramming ; heme metabolism ; δ-aminolevulinic acid ; porphobilinogen ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A metabolomics approach to investigate the proceedings of mitochondrial dysfunction in rats from prediabetes to diabetes

Chun-Feng Huang / Ann Chen / Siao-Yun Lin / Mei-Ling Cheng / Ming-Shi Shiao / Tso-Yen Mao

Saudi Journal of Biological Sciences, Vol 28, Iss 8, Pp 4762-

2021 Volume 4769

Abstract: Background: Diabetes mellitus (DM) is a leading cause of preventable cardiovascular disease, but the metabolic changes from prediabetes to diabetes have not been fully clarified. This study implemented a metabolomics profiling platform to investigate the ...

Abstract	Background: Diabetes mellitus (DM) is a leading cause of preventable cardiovascular disease, but the metabolic changes from prediabetes to diabetes have not been fully clarified. This study implemented a metabolomics profiling platform to investigate the variations of metabolites and to elucidate their global profiling from metabolic syndrome to DM. Methods: Male Sprague-Dawley rats (n = 44) were divided into four groups. Three groups were separately fed with a normal diet, a high-fructose diet (HF), or a high-fat (HL) diet while one group was treated with streptozotocin. The HF and HL diet were meant to induce insulin resistance, obesity, and dyslipidemia, which known to induce DM. Results: The most significant metabolic variations in the DM group’s urine samples were the reduced release of citric acid cycle intermediates, the increase in acylcarnitines, and the decrease in urea excretion, all of which indicated energy metabolism abnormalities and mitochondrial dysfunction. Overall, the metabolic analysis revealed tryptophan metabolic pathway variations in the prediabetic phase, even though the mitochondrial function remains unaffected. Conclusion: This study show that widespread methylations and impaired tryptophan metabolism occur in metabolic syndrome and are then followed by a decline in citric acid cycle intermediates, indicating mitochondrial dysfunction in diabetes.
Keywords	Diabetes ; Metabolic syndrome ; Metabolomics ; Methylation ; Mitochondrial dysfunction ; Prediabetes ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Amino Acid-Based Metabolic Profile Provides Functional Assessment and Prognostic Value for Heart Failure Outpatients

Chao-Hung Wang / Mei-Ling Cheng / Min-Hui Liu / Tieh-Cheng Fu

Disease Markers, Vol

2019 Volume 2019

Abstract: Functional capacity is a crucial parameter correlated with outcomes. The currently used New York Heart Association functional classification (NYHA Fc) system has substantial limitations, leading to inaccurate classification. This study investigated ... ...

Abstract	Functional capacity is a crucial parameter correlated with outcomes. The currently used New York Heart Association functional classification (NYHA Fc) system has substantial limitations, leading to inaccurate classification. This study investigated whether amino acid-based assessment on metabolic status provides an objective way to assess functional capacity and prognosis in heart failure (HF) outpatients. Plasma concentrations of histidine, ornithine, and phenylalanine (HOP) were measured on 890 HF outpatients to assess metabolic status by calculating the HOP score. Cardiopulmonary exercise testing (CPET) was performed in 387 patients to measure metabolic equivalents (MET) in order to define the functional class based on MET (MET Fc). Patients were followed for composite events (death/HF-related rehospitalization) up to one year. We found only 47% concordance between the MET Fc and NYHA Fc. HOP scores worked better than NYHA Fc for discriminating patients with MET Fc II and III from those with MET Fc I, with the optimal cutoff value set at 8.8. HOP scores≥8.8 were associated with risk factors for composite events in different kinds of HF populations and were a powerful predictor of composite events in univariate analysis. In multivariable analysis, HOP scores≥8.8 remained a powerful event predictor, independent of other risk factors. Kaplan-Meier curves revealed that HOP scores of ≥8.8 stratified patients at higher risk of composite events in a variety of HF populations. In conclusion, amino acid-based assessment of metabolic status correlates with functional capacity in HF outpatients and provides prognostic value for a variety of HF populations.
Keywords	Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload

Ying-Chang Tung / Mei-Ling Cheng / Lung-Sheng Wu / Hsiang-Yu Tang / Cheng-Yu Huang / Gwo-Jyh Chang / Chi-Jen Chang

International Journal of Molecular Sciences, Vol 23, Iss 6809, p

Transcriptomics and Metabolomics Analyses

2022 Volume 6809

Abstract: Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat ... ...

Abstract	Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. Male Sprague–Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O -linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF.
Keywords	volume overload ; compensated hypertrophy ; heart failure ; energy metabolism ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Integrated Metabolomic and Transcriptomic Analysis of Acute Kidney Injury Caused by Leptospira Infection

Kuan-Hsing Chen / Li-Fang Chou / Cheng-Chieh Hung / Hsiang-Yu Tang / Mei-Ling Cheng / Huang-Yu Yang / Hsiang-Hao Hsu / Ya-Chung Tian / Chih-Wei Yang

Pathogens, Vol 11, Iss 764, p

2022 Volume 764

Abstract: Renal leptospirosis caused by leptospiral infection is characterised by tubulointerstitial nephritis and tubular dysfunction, resulting in acute and chronic kidney injury. Metabolomic and transcriptomic data from a murine model of Leptospira infection ... ...

Abstract	Renal leptospirosis caused by leptospiral infection is characterised by tubulointerstitial nephritis and tubular dysfunction, resulting in acute and chronic kidney injury. Metabolomic and transcriptomic data from a murine model of Leptospira infection were analysed to determine whether metabolomic data from urine were associated with transcriptome changes relevant to kidney injury caused by Leptospira infection. Our findings revealed that 37 metabolites from the urine of L. interrogans -infected mice had significantly different concentrations than L. biflexa -infected and non-infected control mice. Of these, urinary L-carnitine and acetyl-L-carnitine levels were remarkably elevated in L. interrogans -infected mice. Using an integrated pathway analysis, we found that L-carnitine and acetyl-L-carnitine were involved in metabolic pathways such as fatty acid activation, the mitochondrial L-carnitine shuttle pathway, and triacylglycerol biosynthesis that were enriched in the renal tissues of the L. interrogans -infected mice. This study highlights that L-carnitine and acetyl-L-carnitine are implicated in leptospiral infection-induced kidney injury, suggesting their potential as metabolic modulators.
Keywords	leptospirosis ; metabolomic ; transcriptomic ; acute kidney injury ; ingenuity pathway analysis (IPA) ; Medicine ; R
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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