• Aconitum roots
• Biomarker
• Chuanwu
• Fuzi
• Neuropharmacology
• Neurotoxicology

• Animals
• Humans
• Aconitum/chemistry
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Medicine, Chinese Traditional/methods
• Metabolomics
• Neurotoxicity Syndromes/diagnosis
• Neurotoxicity Syndromes/etiology
• Neurotoxicity Syndromes/metabolism
• Plant Roots

• bioinformatics
• biomarker
• cancer
• metabolic reprogramming
• metabolomics

• Humans
• Neoplasms/metabolism
• Neoplasms/pathology
• Metabolomics/methods
• Metabolic Networks and Pathways
• Animals

• LC–MS
• diagnostic biomarker
• metabolomics
• plasma
• primary aldosteronism

• Humans
• Hyperaldosteronism/blood
• Hyperaldosteronism/diagnosis
• Metabolomics/methods
• Biomarkers/blood
• Female
• Middle Aged
• Male
• Mass Spectrometry/methods
• Chromatography, Liquid/methods
• Metabolome/physiology
• Adult
• Aldosterone/blood
• Liquid Chromatography-Mass Spectrometry

• Chronic Obstructive Pulmonary Disease
• exhaled breath condensate
• mass spectrometry
• metabolomics
• nuclear magnetic resonance

• Humans
• Pulmonary Disease, Chronic Obstructive/metabolism
• Respiratory System/metabolism
• Metabolomics/methods
• Biomarkers/metabolism
• Mass Spectrometry/methods

• biomarker
• disease diagnosis
• pig health
• salivary analytes

• Bioinformatics
• biomarkers
• differentially expressed mRNAs
• differentially expressed miRNAs.
• liver cirrhosis
• metabolome
• transcriptome

• Humans
• Liver Cirrhosis/genetics
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/blood
• MicroRNAs/genetics
• MicroRNAs/blood
• MicroRNAs/metabolism
• Transcriptome
• Male
• Female
• Metabolomics
• Middle Aged
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Metabolome
• Gene Expression Profiling

• 81760383; 82060385 National Natural Science Foundation of China
• 2018FE001(-007) Key Program of Yunnan Applied Basic Research Projects-Joint Special Project
• (202201AY070001-100) Yunnan Provincial Department of Science and Technology
• (2020Y0128, 2019J1255) Yunnan Provincial Department of Education

• chinmedomics
• endocrine diseases
• herbal medicine
• metabolomics

• Humans
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Plants, Medicinal
• Metabolomics/methods

• biomarkers
• oral diseases
• salivaomics
• salivary diagnosis
• systemic diseases

• Humans
• Saliva/chemistry
• Biomarkers/analysis
• Microbiota
• Early Diagnosis
• Biopsy

• biomarkers
• endometriosis
• gas chromatography–mass spectrometry
• metabolomics
• multivariate analysis

• abdominal fat deposition
• liver fat
• obesity phenotypes
• plasma lipidomics
• plasma metabolomics
• tissue insulin resistance

• Metabolomics and translational research
• biomarkers
• cutting-edge techniques
• mass spectrometry
• personalized medicine

• FASN inhibitor
• macitentan
• monocrotaline
• pulmonary hypertension
• rats

• Binding Sites
• Ligands
• Protein Binding
• Proteins/chemistry

• R35 GM118039 NIGMS NIH HHS
• National Institute of General Medical Sciences

• Alzheimer’s disease
• High-resolution mass spectrometry
• Urine metabolites

Dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV) are several important flaviviruses, and infections caused by these flaviviruses remain worldwide health problems. Different flaviviruses exhibit different biological characteristics and pathogenicity. Metabolomics is an emerging research perspective to uncover and observe the pathogenesis of certain infections.

To improve the understanding of the specific metabolic changes that occur during infection with different flaviviruses, considering the principle of noninvasive sampling, this article describes our comprehensive analysis of metabolites in urine samples from the three kinds of flavivirus-infected mice using a liquid chromatography tandem mass spectrometry method to better understand their infection mechanisms.

The urine of DENV-, JEV-, and ZIKV-infected mice had 68, 64, and 47 different differential metabolites, respectively, compared with the urine of control mice. Among the metabolic pathways designed by these metabolites, ABC transporters, arginine and proline metabolism, and regulation of lipolysis play an important role. Furthermore, we predicted and fitted potential relationships between metabolites and pathways.

These virus-specific altered metabolites may be associated with their unique biological properties and pathogenicity. The metabolomic analysis of urine is very important for the analysis of flavivirus infection.

Alzheimer's disease (AD) represents the main form of dementia; however, valid diagnosis and treatment measures are lacking. The discovery of valuable biomarkers through omics technologies can help solve this problem. For this reason, metabolomic analysis using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) was carried out on plasma, hippocampus, and cortex samples of an AD rat model. Based on the metabolomic data, we report a multi-factor combined biomarker screening strategy to rapidly and accurately identify potential biomarkers. Compared with the usual procedure, our strategy can identify fewer biomarkers with higher diagnostic specificity and sensitivity. In addition to diagnosis, the potential biomarkers identified using our strategy were also beneficial for drug evaluation. Multi-factor combined biomarker screening strategy was used to identify differential metabolites from a rat model of amyloid beta peptide 1–40 (Aβ₁₋₄₀) plus ibotenic acid-induced AD (compared with the controls) for the first time; lysophosphatidylcholine (LysoPC) and intermediates of sphingolipid metabolism were screened as potential biomarkers. Subsequently, the effects of donepezil and pine nut were successfully reflected by regulating the levels of the abovementioned biomarkers and metabolic profile distribution in partial least squares-discriminant analysis (PLS-DA). This novel biomarker screening strategy can be used to analyze other metabolomic data to simultaneously enable disease diagnosis and drug evaluation.

•

Multi-factor combined biomarker screening strategy is a novel and rapid metabolomic data processing strategy.

Background: At present, few studies have reported the metabolic profiles of lung tissue in patients with COPD. Our study attempted to analyze the lung metabolome in male COPD patients and to screen the overlapping biomarkers of the lung and plasma metabolomes.

Methods: We performed untargeted metabolomic analysis of normal lung tissue from two independent sets (the discovery set: 20 male COPD patients and 20 controls and the replication set: 47 male COPD patients and 27 controls) and of plasma samples from 80 male subjects containing 40 COPD patients and 40 controls.

Results: We found glycerophospholipids (GPs) and Amino acids were the primary classes of differential metabolites between male COPD patients and controls. The disorders of GPs metabolism and the valine, leucine and isoleucine biosynthesis metabolism pathways were identified in lung discovery set and then also validated in the lung replication set. Combining lung tissue and plasma metabolome, Phytosphingosine and l-tryptophan were two overlapping metabolites biomarkers. Binary logistic regression suggested that phytosphingosine together with l-tryptophan was closely associated with male COPD and showed strong diagnostic power with an AUC of 0.911 (95% CI: 0.8460-0.9765).

Conclusion: Our study revealed the metabolic perturbations of lung tissues from male COPD patients. The detected disorders of GPs and amino acids may provide an insight into the pathological mechanism of COPD. Phytosphingosine and l-tryptophan were two novel metabolic biomarkers for differentiating COPD patients and controls.

• National Natural Science Foundation of China
• Youth Science Foundation, Guangxi Medical University
• Guangxi Medical University

• biomarkers
• chronic disease
• chronic obstructive pulmonary disease
• disability
• metabolomics
• outcome
• rehabilitation

Sow mortality attributable to pelvic organ prolapse (POP) has increased in the U.S. swine industry and continues to worsen. Two main objectives of this study were, (1) to develop a perineal scoring system that can be correlated with POP risk, and (2) identify POP risk-associated biological factors. To assess POP risk during late gestation, sows (n = 213) were scored using a newly developed perineal scoring (PS) system. Sows scored as PS1 (low), PS2 (moderate), or PS3 (high) based on POP risk. Subsequently, 1.5, 0.8, and 23.1% of sows scored PS1, PS2, or PS3, respectively, experienced POP. To identify biomarkers, serum and vaginal swabs were collected from late gestation sows differing in PS. Using GC–MS, 82 serum metabolite differences between PS1 and PS3 animals (P < 0.05) were identified. Vaginal swabs were utilized for 16S rRNA gene sequencing and differences in vaginal microbiomes between PS1 and PS3 animals were detected on a community level (P < 0.01) along with differences in abundances of 89 operational taxonomic units (P < 0.05). Collectively, these data demonstrate that sows with greater POP risk have differential serum metabolites and vaginal microflora. Additionally, an initial and novel characterization of the sow vaginal microbiome was determined.

• Adult
• Amino Acids/blood
• Antipsychotic Agents/therapeutic use
• Asparagine/blood
• Aspartic Acid/blood
• Biogenic Amines/blood
• Chromatography, Liquid/methods
• Early Diagnosis
• Female
• Glutamic Acid/blood
• Glutamine/blood
• Humans
• Male
• Metabolome
• Metabolomics/methods
• Proline/blood
• Schizophrenia/blood
• Schizophrenia/diagnosis
• Schizophrenia/drug therapy
• Tandem Mass Spectrometry/methods
• Taurine/blood
• Young Adult

• Chronic obstructive pulmonary disease
• Gas chromatography-mass spectrometry
• Lung cancer
• Metabolite

Several proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual’s gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.

• Cri du Chat Syndrome
• metabolism
• metabolites
• pathways

• COPD
• Classical therapy
• SNPs
• complexity
• eosinophils
• personalized-medicine
• real-life analysis
• systems approaches.

• aging
• biobehavioral mechanisms
• chronic venous ulcers
• chronic wounds
• symptoms

A traditional Chinese tea with many pharmacological effects, vine tea (VT) is considered a potential dietary supplement to improve type 2 diabetes (T2D). To investigate the effect and mechanism of VT on glucose and lipid metabolic disorders in T2D rats, Wistar rats fed a normal diet served as the normal control, while rats fed a high-fat diet combined with low-dose streptozotocin (STZ)-induced T2D were divided into three groups: The model group (MOD); the positive control group (MET, metformin at 200 mg/kg/d); and the VT-treated group (VT500, allowed to freely drink 500 mg/L VT). After four weeks of intervention, biochemical metrics indicated that VT significantly ameliorated hyperglycemia, hyperlipidemia and hyperinsulinemia in T2D rats. Metabolomics research indicated that VT regulated the levels of metabolites closely related to glucose and lipid metabolism and promoted glycogen synthesis. Furthermore, VT had a significant influence on the expression of key genes involved in the Akt signaling pathway, inhibited gluconeogenesis through the Akt/Foxo1/Pck2 signaling pathway, and reduced fatty acid synthesis via the SREBP1c/Fasn signaling pathways. In conclusion, VT has great potential as a dietary supplement to ameliorate glucose and lipid metabolic disorders via the Akt signaling pathway in T2D rats.

• Akt signaling pathway
• glucose and lipid metabolic disorders
• metabolomics
• type 2 diabetes
• vine tea

• Animals
• Biomarkers
• Carbohydrate Metabolism/drug effects
• Diabetes Mellitus, Experimental
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/etiology
• Diabetes Mellitus, Type 2/metabolism
• Dietary Supplements
• Disease Models, Animal
• Glucose/metabolism
• Lipid Metabolism/drug effects
• Liver/drug effects
• Liver/metabolism
• Metabolome
• Metabolomics/methods
• Proto-Oncogene Proteins c-akt/metabolism
• Rats
• Signal Transduction/drug effects
• Tea/chemistry

• Animals
• Cats/metabolism
• Diet/veterinary
• Female
• Metabolome
• Urine/chemistry

• This study was supported by The Autzen Foundation and John and Ruth Ottmar Memorial Endowment intramural funds from the College of Veterinary Medicine at Washington State University.

Caowu (Radix Aconiti kusnezoffii, CW), the root of Aconitum kusnezoffii Reichb., has widely used clinically in rheumatic arthritis, painful joints, and tumors for thousands of years. However, the toxicity of heart and central nervous system induced by CW still limited the application.

Metabolomics was performed to identify the sensitive and reliable biomarkers and to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity, and the detoxification by combinatorial intervention of CW with Gancao (Radix Glycyrrhizae) (CG), Baishao (Radix Paeoniae Alba) (CB), and Renshen (Radix Ginseng) (CR) was also analyzed by pattern recognition methods.

As a result, the metabolites were characterized and responsible for pentose and glucuronate interconversions, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, taurine and hypotaurine metabolism, fructose and mannose metabolism, and starch and sucrose metabolism, six networks of which were the same to the metabolic pathways of Chuanwu (Radix Aconiti, CHW) group. The ascorbate and aldarate metabolism was also characterized by CW group. The urinary metabolomics also revealed CW-induced serious toxicity to heart and liver. Thirteen significant metabolites were identified and had validated as phenotypic toxicity biomarkers of CW, five biomarkers of which were commonly owned in Aconitum. The changes of toxicity metabolites obtained from combinatorial intervention of CG, CB, and CR also were analyzed to investigate the regulation degree of toxicity biomarkers adjusted by different combinatorial interventions at 6^th month.

Metabolomics analyses coupled with pattern recognition methods in the evaluation of drug toxicity and finding detoxification methods were highlighted in this work.

Metabolomics was performed to characterize the biochemical potential mechanisms of Caowu toxicity

Abbreviations used: CW: Caowu (Radix Aconiti kusnezoffii); CHW: Chuanwu (Radix Aconiti); TCM: Traditional Chinese Medicine; CG: Caowu and Gancao; CB: Caowu and Baishao; CR: Caowu and Renshen; QC: Quality control; UPLC: Ultra performance liquid chromatography; MS: Mass spectrometry; PCA: Principal component analysis; PLS-DA: Partial least squares-discriminant analysis; OPLS: Orthogonal projection to latent structures analysis.

• Aconitum
• biomarkers
• detoxification
• mass spectrometry
• metabolomics
• toxicity
• traditional Chinese Medicine

“RenqingMangjue” pill (RMP), as an effective prescription of Traditional Tibetan Medicine (TTM), has been widely used in treating digestive diseases and ulcerative colitis for over a thousand years. In certain classical Tibetan Medicine, heavy metal may add as an active ingredient, but it may cause contamination unintentionally in some cases. Therefore, the toxicity and adverse effects of TTM became to draw public attention. In this study, 48 male Wistar rats were orally administrated with different dosages of RMP once a day for 15 consecutive days, then half of the rats were euthanized on the 15th day and the remaining were euthanized on the 30th day. Plasma, kidney and liver samples were acquired to ¹H NMR metabolomics analysis. Histopathology and ICP-MS were applied to support the metabolomics findings. The metabolic signature of plasma from RMP-administrated rats exhibited increasing levels of glucose, betaine, and creatine, together with decreasing levels of lipids, 3-hydroxybutate, pyruvate, citrate, valine, leucine, isoleucine, glutamate, and glutamine. The metabolomics analysis results of liver showed that after RMP administration, the concentrations of valine, leucine, proline, tyrosine, and tryptophan elevated, while glucose, sarcosine and 3-hydroxybutyrate decreased. The levels of metabolites in kidney, such as, leucine, valine, isoleucine and tyrosine, were increased, while taurine, glutamate, and glutamine decreased. The study provides several potential biomarkers for the toxicity mechanism research of RMP and shows that RMP may cause injury in kidney and liver and disturbance of several pathways, such as energy metabolism, oxidative stress, glucose and amino acids metabolism.

• 1H NMR
• ICP-MS
• metabolomics
• toxicity
• “RenqingMangjue” pill

• HPLC-ESI-TOF-MS
• Hepatocellular carcinoma
• Metabolomics
• Shuihonghuazi Formula

• Animals
• Bile Acids and Salts/metabolism
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/pathology
• Chromatography, High Pressure Liquid/methods
• Discriminant Analysis
• Drugs, Chinese Herbal/pharmacology
• Least-Squares Analysis
• Lipid Metabolism/drug effects
• Liver Neoplasms, Experimental/drug therapy
• Liver Neoplasms, Experimental/pathology
• Male
• Medicine, Chinese Traditional
• Metabolomics/methods
• Principal Component Analysis
• Rats
• Rats, Sprague-Dawley
• Spectrometry, Mass, Electrospray Ionization/methods

• Biomarkers
• Cancer
• Exosomes
• Saliva

Acupuncture is an alternative therapy that is widely used to treat various diseases. However, detailed biological interpretation of the acupuncture stimulations is limited. We here used metabolomics and proteomics technology, thereby identifying the serum small molecular metabolites into the effect and mechanism pathways of standardized acupuncture treatments at ‘Zusanli’ acupoint which was the most often used acupoint in previous reports. Comprehensive overview of serum metabolic profiles during acupuncture stimulation was investigated. Thirty-four differential metabolites were identified in serum metabolome and associated with ten metabolism pathways. Importantly, we have found that high impact glycerophospholipid metabolism, fatty acid metabolism, ether lipid metabolism were acutely perturbed by acupuncture stimulation. As such, these alterations may be useful to clarify the biological mechanism of acupuncture stimulation. A series of differentially expressed proteins were identified and such effects of acupuncture stimulation were found to play a role in transport, enzymatic activity, signaling pathway or receptor interaction. Pathway analysis further revealed that most of these proteins were found to play a pivotal role in the regulation of multiple metabolism pathways. It demonstrated that the metabolomics coupled with proteomics as a powerful approach for potential applications in understanding the biological effects of acupuncture stimulation.

Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer.

• Glucose metabolism
• Warburg effect
• Metabolomics
• Gastric cancer
• Biomarker
• Therapy

• Animals
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/metabolism
• Cell Hypoxia
• Cell Proliferation
• Glucose/metabolism
• Glycolysis/drug effects
• Humans
• Metabolomics
• Molecular Targeted Therapy
• Signal Transduction
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Tumor Microenvironment

• Animals
• Biomarkers/analysis
• Diagnosis, Oral/methods
• Early Diagnosis
• Humans
• Precision Medicine/methods
• Saliva/chemistry

• R01 CA139596 NCI NIH HHS
• R01 DE17170 NIDCR NIH HHS
• R21 CA0126733 NCI NIH HHS
• R56 DE23241 NIDCR NIH HHS
• U01DE17593 NIDCR NIH HHS
• UH2TR000923 NCATS NIH HHS

This paper was designed to investigate the phenotypic characterization of Nanshi Oral Liquid (NOL) alters metabolic signatures of the ‘Kidney Yang Deficiency syndrome’ (KYDS). Urine metabolites were profiled by UPLC-ESI-Q-TOF-HDMS. The significantly changed metabolites such as xanthurenic acid, 4,8-dihydroxyquinoline, 3-methyldioxyindole, 4,6-dihydroxyquinoline, kynurenic acid, hippuric acid, taurine, tyramine, and 3-metanephrine, had been identified, and were related to the disturbance in tyrosine metabolism, steroid hormone biosynthesis, taurine and hypotaurine metabolism, tryptophan metabolism, phenylalanine metabolism and lysine degradation, which were helpful to further understanding the KYDS and intervention mechanism of NOL. The biochemical result showed that NOL can alleviate the kidney impairment induced by KYDS. Metabolomics results indicated the significantly changed metabolites were found to be reasonable in explaining the action mechanism of NOL. Interestingly, the effectiveness of NOL against KYDS was proved using the established metabolomics method and regulated the biomarkers as well as adjusted the metabolic disorder pathways. NOL had potentially pharmacological effect through regulating multiple perturbed pathways to normal state. This work showed that the metabolomics method was a powerful approach for studying the phenotypic characterization of disease’s syndrome during disease prevention and its intervention mechanism.

There is a lack of diagnostic tests for cholangiocarcinoma. This report identifies 4 serum metabolites which could differentiate cholangiocarcinoma patients with high accuracy.

Extrahepatic cholangiocarcinoma (ECC) is the second most common type of malignant primary tumor with a poor survival rate and an increasing global trend.

• blister fluid
• mass spectrometry
• metabolomics
• nuclear magnetic resonance
• pediatric burns
• proteomics

• Adult
• Aged
• Aged, 80 and over
• Biopsy, Large-Core Needle/standards
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/surgery
• Female
• Humans
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Neoplasm Grading
• Predictive Value of Tests

Breast cancer is a global health issue, and as the tumor burden increases, we need to come up with newer, better technologies which are convenient, cheap, rapid, sensitive with a high specificity. Technological advancements in the field of cancer biomarker has led to the development of techniques such as mass spectrometric analysis and microarray analysis in which genes, proteins and hundreds and thousands of metabolites can be identified with the emergence of genomics, proteomics and metabolomics. This research is focused on finding biomarkers for diagnosis, prognosis, staging, treatment response and targets for chemotherapy, generating a panel of markers which provide better clinical information compared to a single marker in the panel. This review briefly summarizes application of genomics and proteomics followed by key concepts and applications of metabolomics in breast cancer, with the conclusion that an integration of the three “OMIC” technologies may hold the key to future biomarker discovery.

• ASCO – American Society of Clinical Oncology
• Biomarker
• Breast cancer
• CA – cancer antigen
• Cdx-2 – caudal type homebox 2
• ER – estrogen receptor
• FDA – Federal Drug Authority
• GC-TOF-MS – time of flight
• GPCho – glycerophosphocholine
• Genomics
• HER2 – human epidermal growth factor receptor 2
• HMDB – Human metabolome database
• KAL1 – Kallman syndrome 1 sequence
• KiSS1 – Kisspeptin 1
• LC/ESI-MS – electrospray ionization
• MINDACT – Microarray InNode Negative Disease may Avoid ChemoTherapy using Mammaprint–
• Metabolomics
• NIST – National Institute of Standards and Technology
• PCho – phosphocholine
• PgR – progesterone receptor
• Proteomics
• TAILORx – Trial Assigning Individualized Options for Treatment (Rx)