The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide. Because of the limited success of generic interventions, the focus of the disease study has shifted toward... Show moreThe prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide. Because of the limited success of generic interventions, the focus of the disease study has shifted toward personalized strategies, particularly in the early stages of the disease. Traditional Chinese medicine (TCM) is based on a systems view combined with personalized strategies and has improved our knowledge of personalized diagnostics. From a systems biology perspective, the understanding of personalized diagnostics can be improved to yield a biochemical basis for such strategies; for example, metabolomics can be used in combination with other system-based diagnostic methods such as ultra-weak photon emission (UPE). In this study, we investigated the feasibility of using plasma metabolomics obtained from 44 pre-T2DM subjects to stratify the following TCM-based subtypes: Qi-Yin deficiency, Qi-Yin deficiency with dampness, and Qi-Yin deficiency with stagnation. We studied the relationship between plasma metabolomics and UPE with respect to TCM-based subtyping in order to obtain biochemical information for further interpreting disease subtypes. Principal component analysis of plasma metabolites revealed differences among the TCM-based pre-T2DM subtypes. Relatively high levels of lipids (e.g., cholesterol esters and triglycerides) were important discriminators of two of the three subtypes and may be associated with a higher risk of cardiovascular disease. Plasma metabolomics data indicate that the lipid profile is an essential component captured by UPE with respect to stratifying subtypes of T2DM. The results suggest that metabolic differences exist among different TCM-based subtypes of pre-T2DM, and profiling plasma metabolites can be used to discriminate among these subtypes. Plasma metabolomics thus provides biochemical insights into system-based UPE measurements. (C) 2019 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company. Show less
Draper, C.F.; Duisters, K.L.W.; Weger, B.; Chakrabarti, A.; Harms, A.C.; Brennan, L.; ... ; Greef, J. van der 2019
The menstrual cycle is an essential life rhythm governed by interacting levels of progesterone, estradiol, follicular stimulating, and luteinizing hormones. To study metabolic changes, biofluids... Show moreThe menstrual cycle is an essential life rhythm governed by interacting levels of progesterone, estradiol, follicular stimulating, and luteinizing hormones. To study metabolic changes, biofluids were collected at four timepoints in the menstrual cycle from 34 healthy, premenopausal women. Serum hormones, urinary luteinizing hormone and self-reported menstrual cycle timing were used for a 5-phase cycle classification. Plasma and urine were analyzed using LC-MS and GC-MS for metabolomics and lipidomics; serum for clinical chemistries; and plasma for B vitamins using HPLC-FLD. Of 397 metabolites and micronutrients tested, 208 were significantly (p < 0.05) changed and 71 reached the FDR 0.20 threshold showing rhythmicity in neurotransmitter precursors, glutathione metabolism, the urea cycle, 4-pyridoxic acid, and 25-OH vitamin D. In total, 39 amino acids and derivatives and 18 lipid species decreased (FDR < 0.20) in the luteal phase, possibly indicative of an anabolic state during the progesterone peak and recovery during menstruation and the follicular phase. The reduced metabolite levels observed may represent a time of vulnerability to hormone related health issues such as PMS and PMDD, in the setting of a healthy, rhythmic state. These results provide a foundation for further research on cyclic differences in nutrient-related metabolites and may form the basis of novel nutrition strategies for women. Show less
Rossetto Burgos, R.C.; Ramautar, R.; Wijk, E.P.A. van; Hankemeier, T.; Greef, J. van der; Mashaghi Tabari, A. 2018
Acute myeloid leukemia (AML) is a blood cancer that is caused by a disorder of the process that normally generates neutrophils. Function and dysfunction of neutrophils are key to physiologic... Show moreAcute myeloid leukemia (AML) is a blood cancer that is caused by a disorder of the process that normally generates neutrophils. Function and dysfunction of neutrophils are key to physiologic defense against pathogens as well as pathologies including autoimmunity and cancer. A major mechanism through which neutrophils contribute to health and disease is oxidative burst, which involves rapid release of reactive oxygen species (ROS) generated by a chemical reaction network catalyzed by enzymes including NADPH oxidase and myeloperoxidase (MPO). Due to the involvement of neutrophil-derived reactive oxygen species in many diseases and importance of NADPH oxidase and MPO-mediated reactions in progression and treatment of myeloid leukemia, monitoring this process and modulating it by pharmacological interventions is of great interest. In this work, we have evaluated the potential of a label-free method using ultra-weak photon emission (UPE) to monitor ROS production in neutrophil-like HL60 myeloid leukemia cells. Suppression of ROS was achieved by several drug candidates that target different parts of the reaction pathway. Our results show that UPE can report on ROS production as well as suppression by pharmacological inhibitors. We find that UPE is primarily generated by MPO catalyzed reaction and thus will be affected when an upstream reaction is pharmacologically modulated. Show less
Rossetto Burgos, R.C.; Zhang, W.; Wijk, E.P.A. van.; Hankemeier, T.; Ramautar, R.; Greef, J. van der 2017
The increasing prevalence of rheumatoid arthritis has driven the development of new approaches and technologies for investigating the pathophysiology of this devastating, chronic disease. From the... Show moreThe increasing prevalence of rheumatoid arthritis has driven the development of new approaches and technologies for investigating the pathophysiology of this devastating, chronic disease. From the perspective of systems biology, combining comprehensive personal data such as metabolomics profiling with ultra-weak photon emission (UPE) data may provide key information regarding the complex pathophysiology underlying rheumatoid arthritis. In this article, we integrated UPE with metabolomics-based technologies in order to investigate collagen-induced arthritis, a mouse model of rheumatoid arthritis, at the systems level, and we investigated the biological underpinnings of the complex dataset. Using correlation networks, we found that elevated inflammatory and ROS-mediated plasma metabolites are strongly correlated with a systematic reduction in amine metabolites, which is linked to muscle wasting in rheumatoid arthritis. We also found that increased UPE intensity is strongly linked to metabolic processes (with correlation co-efficiency |r| value >0.7), which may be associated with lipid oxidation that related to inflammatory and/or ROS-mediated processes. Together, these results indicate that UPE is correlated with metabolomics and may serve as a valuable tool for diagnosing chronic disease by integrating inflammatory signals at the systems level. Our correlation network analysis provides important and valuable information regarding the disease process from a system-wide perspective. Show less
He, M.; Harms, A.C.; Wijk, E.P.A. van; Wang, M.; Berger, R.; Koval, V.V.; ... ; Greef, J. van der 2017
Oxidised lipids, covering enzymatic and auto-oxidation-synthesised mediators, are important signalling metabolites in inflammation while also providing a readout for oxidative stress, both of... Show moreOxidised lipids, covering enzymatic and auto-oxidation-synthesised mediators, are important signalling metabolites in inflammation while also providing a readout for oxidative stress, both of which are prominent physiological processes in a plethora of diseases. Excretion of these metabolites via urine is enhanced through the phase-II conjugation with glucuronic acid, resulting in increased hydrophilicity of these lipid mediators. Here, we developed a bovine liver-β-glucuronidase hydrolysing sample preparation method, using liquid chromatography coupled to tandem mass spectrometry to analyse the total urinary oxidised lipid profile including the prostaglandins, isoprostanes, dihydroxy-fatty acids, hydroxy-fatty acids and the nitro-fatty acids. Our method detected more than 70 oxidised lipids biosynthesised from two non-enzymatic and three enzymatic pathways in urine samples. The total oxidised lipid profiling method was developed and validated for human urine and was demonstrated for urine samples from patients with rheumatoid arthritis. Pro-inflammatory mediators PGF2α and PGF3α and oxidative stress markers iPF2α- IV, 11-HETE and 14-HDoHE were positively associated with improvement of disease activity score. Furthermore, the anti-inflammatory nitro-fatty acids were negatively associated with baseline disease activity. In conclusion, the developed methodology expands the current metabolic profiling of oxidised lipids in urine, and its application will enhance our understanding of the role these bioactive metabolites play in health and disease. Show less
He, M.; Sun, M.; Wijk, E.P.A. van; Wietmarschen, H.A. van; Wijk, R.; Wang, Z.; ... ; Greef, J. van der 2016
To present the possibilities pertaining to linking ultra-weak photon emission (UPE) with Chinese medicine-based diagnostics principles, we conducted a review of Chinese literature regarding UPE... Show moreTo present the possibilities pertaining to linking ultra-weak photon emission (UPE) with Chinese medicine-based diagnostics principles, we conducted a review of Chinese literature regarding UPE with respect to a systems view of diagnostics. Data were summarized from human clinical studies and animal models published from 1979 through 1998. The research fields can be categorized as follows: (1) human physiological states measured using UPE; (2) characteristics of human UPE in relation to various pathological states; and (3) the relationship between diagnosis (e.g., Chinese syndromes) and the dynamics of UPE in animal models. We conclude that UPE has clear potential in terms of understanding the systems view on health and disease as described using Chinese medicine-based diagnostics, particularly from a biochemistry-based regulatory perspective. Linking UPE with metabolomics can further bridge biochemistry-based Western diagnostics with the phenomenology-based Chinese diagnostics, thus opening new avenues for studying systems diagnostics in the early stage of disease, for prevention-based strategies, as well as for systems-based intervention in chronic disease. Show less
Sun, M.; Li, L; Wang, M.; Wijk, E.P.A. van; He, M.; Wijk, R. van; ... ; Wei, S. 2016
To improve the quality control of herbal drugs, there has been a major shift from evaluating individual chemicals to evaluating multiple-constituent chemicals, given the multi-pharmacology nature... Show moreTo improve the quality control of herbal drugs, there has been a major shift from evaluating individual chemicals to evaluating multiple-constituent chemicals, given the multi-pharmacology nature of herbal drugs. Therefore, rapid, systematic assays are needed in order to assess the quality of medicinal herbs using a comprehensive, integrated approach. Light-induced delayed luminescence (DL) is used to measure decaying long-term ultra-weak photon emissions following excitation with light. DL is considered to be a sensitive indicator for characterizing the properties of biological systems and herbal medicines with various therapeutic properties. The aim of this study was to examine the feasibility of using DL as a novel quality-assessment tool using rhubarb material as a model system, and to establish the correlation between DL parameters and the chemical constituents of rhubarb. Raw roots and rhizomes were collected from rhubarb (Rheum palmatum L.) at various elevations in western China. HPLC analysis was used to identify fourteen bioactive constituents. Five DL parameters were calculated from the DL decay curves of the rhubarb samples. Statistical tools, including principal component analysis, were used to classify the rhubarb samples using data obtained using two different assays. Finally, Spearman's correlation coefficient was calculated to quantify the correlation between the bioactive compounds and corresponding DL parameters. We found that both the chemical analysis and DL measurements reflect variations in the quality of rhubarb due to environment factor. The DL parameters were correlated significantly with the bioactive chemical constituents. Our results indicate that DL is a promising tool for evaluating multiple constituents and for assessing the therapeutic properties of herbal medicines. Thus, DL may be used as part of a comprehensive system for assessing the quality and/or therapeutic properties of herbal medicines. Show less
He, M.; Wijk, E.P.A. van; Berger, R.; Wang, M.; Strassburg, K.; Schoeman, J.C.; ... ; Greef, J. van der 2015
