Plasma metabolites in treatment-requiring retinopathy of prematurity: Potential biomarkers identified by metabolomics

An apolipoprotein A-I mimetic peptide, D-4F, has been shown to improve vasodilation and inhibit atherosclerosis in hypercholesterolemic low-density lipoprotein receptor-null (LDLr−/−) mice. To study the metabolic variations of D-4F ininhibiting atherosclerosis, metabonomics, a novel system biological strategy to investigate the pathogenesis, was developed. Female LDLr−/− mice were fed a Western diet and injected with or without D-4F intraperitoneally. Atherosclerotic lesion formation was measured, whereas plasma metabolic profiling was obtained on the basis of ultra-high-performance liquid chromatography in tandem with time-of-flight mass spectrometry operating in both positive and negative ion modes. Data were processed by multivariate statistical analysis to graphically demonstrate metabolic changes. The partial least-squares discriminate analysis model was validated with cross-validation and permutation tests to ensure the model's reliability. D-4F significantly inhibited the formation of atherosclerosis in a time-dependent manner. The metabolic profiling was altered dramatically in hypercholesterolemic LDLr−/− mice, and a significant metabolic profiling change in response to D-4F treatment was observed in both positive and negative ion modes. Thirty-six significantly changed metabolites were identified as potential biomarkers. A series of phospholipid metabolites, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE), phosphatidylcholine (PC), phatidylethanolamine (PE), sphingomyelin (SM), and diacylglycerol (DG), particularly the long-chain LysoPC, was elevated dramatically in hypercholesterolemic LDLr−/− mice but reduced by D-4F in a time-dependent manner. Quantitative analysis of LysoPC, LysoPE, PC, and DG using HPLC was chosen to validate the variation of these potential biomarkers, and the results were consistent with the metabonomics findings. Our findings demonstrated that D-4F may inhibit atherosclerosis by regulating phospholipid metabolites specifically by decreasing plasma long-chain LysoPC.

Download Full-text

High-Throughput Metabolomics for Discovering Potential Biomarkers and Identifying Metabolic Mechanisms in Aging and Alzheimer’s Disease

10.21203/rs.3.rs-60073/v1 ◽

2020 ◽

Author(s):

Kun Xie ◽

Qi Qin ◽

Zhiping Long ◽

Yihui Yang ◽

Chenghai Peng ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Stearic Acid ◽

Natural Aging ◽

Aging Population ◽

Plasma Metabolites ◽

Pathway Enrichment Analysis ◽

Proline Metabolism ◽

Early Screening ◽

Potential Biomarkers

Abstract Background and Aims: Alzheimer’s disease (AD) is an aging-related neurodegenerative disease. The current diagnosis of AD may fail to identify a substantial number of asymptomatic individuals who will progress to AD. We aimed to investigate the metabolic mechanisms of aging and AD and to identify potential biomarkers for the early screening of AD in a natural aging population.Methods: To analyse the plasma metabolites related to aging, we conducted an untargeted metabolomics analysis using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry in a two-stage cross-sectional study. Spearman’s correlation analysis and random forest were applied to model the relationship between age and each metabolite. Moreover, systematic reviews of metabolomics studies of AD in the PubMed, Cochrane and Embase databases were searched to extract the differential metabolites and altered pathways from original studies. Pathway enrichment analysis was conducted using Mummichog.Results: In total, 669 metabolites were significantly altered with aging, and thirteen pathways were enriched and correlated with aging. Five metabolites (palmitic acid, stearic acid, linoleic acid, glutamine, and oleic acid) were identified as potential biomarkers for AD based on a systematic review. Arginine and histidine were considered candidate monitoring markers of disease progression in the mild cognitive impairment (MCI) population. Moreover, three pathways (purine metabolism, arginine and proline metabolism, and the TCA cycle) were shared between aging and AD. Arginine and proline metabolism play a key role in the progression from CN to MCI and to AD in the natural aging population. Three metabolites, 16-a-hydroxypregnenolone, stearic acid and PC (16:0/22:5(4Z,7Z,10Z,13Z,16Z)), were finally proposed as potential markers of AD in the natural aging population.Conclusion: The underlying mechanism shared between aging and AD and the potential biomarkers for AD diagnosis were proposed based on multistep comparative analysis.

Download Full-text

High-Throughput Metabolomics for Discovering Potential Biomarkers and Identifying Metabolic Mechanisms in Aging and Alzheimer’s Disease

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.602887 ◽

2021 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Kun Xie ◽

Qi Qin ◽

Zhiping Long ◽

Yihui Yang ◽

Chenghai Peng ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Natural Aging ◽

Aging Population ◽

Plasma Metabolites ◽

Pathway Enrichment Analysis ◽

Proline Metabolism ◽

Early Screening ◽

Cross Sectional ◽

Potential Biomarkers

Alzheimer’s disease (AD) is an aging-related neurodegenerative disease. We aimed to investigate the metabolic mechanisms of aging and AD and to identify potential biomarkers for the early screening of AD in a natural aging population. To analyze the plasma metabolites related to aging, we conducted an untargeted metabolomics analysis using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry in a two-stage cross-sectional study. Spearman’s correlation analysis and random forest were applied to model the relationship between age and each metabolite. Moreover, a systematic review of metabolomics studies of AD in the PubMed, Cochrane and Embase databases were searched to extract the differential metabolites and altered pathways from original studies. Pathway enrichment analysis was conducted using Mummichog. In total, 669 metabolites were significantly altered with aging, and 12 pathways were enriched and correlated with aging. Three pathways (purine metabolism, arginine and proline metabolism, and the TCA cycle) were shared between aging and AD. Arginine and proline metabolism play a key role in the progression from healthy to mild cognitive impairment and to AD in the natural aging population. Three metabolites, 16-a-hydroxypregnenolone, stearic acid and PC[16:0/22:5(4Z,7Z,10Z,13Z,16Z)] were finally proposed as potential markers of AD in the natural aging population. The underlying mechanism shared between aging and AD and the potential biomarkers for AD diagnosis were proposed based on multistep comparative analysis.

Download Full-text

Plasma Metabolomic Profiling in Workers With Noise-induced Hearing Loss: A Pilot Study

10.21203/rs.3.rs-437429/v1 ◽

2021 ◽

Author(s):

Long Miao ◽

Boshen Wang ◽

Juan Zhang ◽

Lihong Yin ◽

Yuepu Pu

Keyword(s):

Hearing Loss ◽

Acid Metabolism ◽

White Blood Cells ◽

Partial Least Square ◽

Plasma Metabolites ◽

Control Group ◽

Mrna Levels ◽

Noise Induced Hearing Loss ◽

Autophagy Pathway ◽

Potential Biomarkers

Abstract Noise-induced hearing loss (NIHL) remains a leading occupational related disease and is a serious public health problem. Hence, the identification of potential biomarkers for NIHL prevention and diagnosis has become an urgent work. To discover potential metabolic biomarkers of NIHL, plasma metabolomics analysis among 62 NIHL patients and 62 controls was performed using ultrahigh performance liquid chromatography-mass spectrometry (UPLC/MS). Orthogonal partial least square-discriminant analysis (OPLS-DA) model was applied to distinguish metabolite profile alterations in plasma samples between the two groups. The alterations in autophagy pathway were in accordance with previous published studies, therefore, three autophagy-related genes (PI3K, AKT and ATG5) were selected and mRNA levels were detected by RT-qPCR analysis in peripheral white blood cells (WBCs) samples. Compared to the control group, 20 identified plasma metabolites were significantly altered in NIHL patients. Meanwhile, a total of seven metabolic pathways were enriched, including glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, autophagy, choline metabolism, alpha-linolenic acid metabolism and linoleic acid metabolism, and retrograde endocannabinoid signaling pathway. Furthermore, the results indicated that the mRNA levels of three autophagy-related genes (PI3K, AKT and ATG5) were significantly decreased in NIHL cases compared with controls. Taken together, our current study firstly provides evidence that the identified aberrantly altered metabolites might be potential biomarkers of NIHL for noise-exposed workers. In addition, autophagy pathway may be involved in the occurrence and development of NIHL.

Download Full-text

Alterations in Metabolome and Microbiome Associated with an Early Stress Stage in Male Wistar Rats: A Multi-Omics Approach

International Journal of Molecular Sciences ◽

10.3390/ijms222312931 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12931

Author(s):

Julia Hernandez-Baixauli ◽

Pere Puigbò ◽

Nerea Abasolo ◽

Hector Palacios-Jordan ◽

Elisabet Foguet-Romero ◽

...

Keyword(s):

Biochemical Characterization ◽

The United States ◽

Stress Disorders ◽

Plasma Metabolites ◽

Mild Stress ◽

Potential Candidate ◽

Urine Metabolites ◽

Early Stress ◽

Threonic Acid ◽

Potential Biomarkers

Stress disorders have dramatically increased in recent decades becoming the most prevalent psychiatric disorder in the United States and Europe. However, the diagnosis of stress disorders is currently based on symptom checklist and psychological questionnaires, thus making the identification of candidate biomarkers necessary to gain better insights into this pathology and its related metabolic alterations. Regarding the identification of potential biomarkers, omic profiling and metabolic footprint arise as promising approaches to recognize early biochemical changes in such disease and provide opportunities for the development of integrative candidate biomarkers. Here, we studied plasma and urine metabolites together with metagenomics in a 3 days Chronic Unpredictable Mild Stress (3d CUMS) animal approach that aims to focus on the early stress period of a well-established depression model. The multi-omics integration showed a profile composed by a signature of eight plasma metabolites, six urine metabolites and five microbes. Specifically, threonic acid, malic acid, alpha-ketoglutarate, succinic acid and cholesterol were proposed as key metabolites that could serve as key potential biomarkers in plasma metabolome of early stages of stress. Such findings targeted the threonic acid metabolism and the tricarboxylic acid (TCA) cycle as important pathways in early stress. Additionally, an increase in opportunistic microbes as virus of the Herpesvirales was observed in the microbiota as an effect of the primary stress stages. Our results provide an experimental biochemical characterization of the early stage of CUMS accompanied by a subsequent omic profiling and a metabolic footprinting that provide potential candidate biomarkers.

Download Full-text

Plasma metabolites Xanthine, 4-Pyridoxate, and d-glutamic acid as novel potential biomarkers for pulmonary tuberculosis

Clinica Chimica Acta ◽

10.1016/j.cca.2019.08.017 ◽

2019 ◽

Vol 498 ◽

pp. 135-142 ◽

Cited By ~ 1

Author(s):

Huai Huang ◽

Li-Ying Shi ◽

Li-Liang Wei ◽

Yu-Shuai Han ◽

Wen-Jing Yi ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Glutamic Acid ◽

Plasma Metabolites ◽

Potential Biomarkers

Download Full-text

Plasma Metabolomics Reveals Pathogenesis of Retained Placenta in Dairy Cows

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.697789 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yuqiong Li ◽

Zhengwei Zhao ◽

Yang Yu ◽

Xiaojun Liang ◽

Shengyi Wang ◽

...

Keyword(s):

Antioxidant Capacity ◽

Dairy Cows ◽

Metabolic Pathways ◽

Reproductive Hormones ◽

Plasma Metabolites ◽

Treatment Schedule ◽

Multivariate Statistical ◽

Retained Placenta ◽

Th2 Cytokine ◽

Potential Biomarkers

The complex etiology and pathogenesis of retained placenta (RP) bring huge challenges for researchers and clinical veterinarians in investigating the pathogenesis and treatment schedule. This study aims to investigate the pathogenesis of RP in dairy cows by plasma metabolomics. As subjects, 10 dairy cows with RP and 10 healthy dairy cows were enrolled according to strict enrollment criteria. Imbalanced antioxidant capacity, reduced Th1/Th2 cytokine ratio, and deregulation of total bilirubin (T-bil), alkaline phosphatase (ALP), and reproductive hormones were shown in dairy cows with RP by detecting biochemical indicators, oxidation and antioxidant markers, and cytokines in serum. Plasma metabolites were detected and analyzed by a liquid chromatography–mass spectrometry (LC–MS) system coupled with multivariate statistical analysis software. A total of 23 potential biomarkers were uncovered in the plasma of dairy cows with RP. The metabolic pathways involved in these potential biomarkers are interconnected, and the conversion, utilization, and excretion of nitrogen were disturbed in dairy cows with RP. Moreover, these potential biomarkers are involved in the regulation of antioxidant capacity, inflammation, and autocrine or paracrine hormone. All of these findings suggest that an imbalance of these potential biomarkers might be responsible for the imbalanced antioxidant capacity, reduced Th1/Th2 cytokine ratio, and deregulation of reproductive hormones in dairy cows with RP. The regulation of metabolic pathways involved in these potential biomarkers represents a promising therapeutic strategy for RP.

Download Full-text