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ABSTRACT: Metabolites have played an essential role in our understanding of life, health, and disease for thousands of years. This domain became much more important after the concept of metabolism was discovered. In the 1950s, mass spectrometry was coupled to chromatography and made the technique more application-oriented and allowed the development of new profiling technologies. Since 1980, TNO has performed system-based metabolic profiling of body fluids, and combined with pattern recognition has led to many discoveries and contributed to the field known as metabolomics and systems biology. This review describes the development of related concepts and applications at TNO in the biomedical, pharmaceutical, nutritional, and microbiological fields, and provides an outlook for the future. © 2013 Wiley Periodicals, Inc. Mass Spec Rev.Mass Spectrometry Reviews 04/2013; · 10.46 Impact Factor
Herman van Wietmarschen, Jan van der Greef[show abstract] [hide abstract]
ABSTRACT: Metabolites play numerous roles in the healthy and diseased body, ranging from regulating physiological processes to providing building blocks for the body. Therefore, understanding the role of metabolites is important in elucidating the etiology and pathology of diseases and finding targets for new treatment options. Rheumatoid arthritis is a complex chronic disease for which new disease management strategies are needed. The aim of this review is to bring together and integrate information about the various roles that metabolites have in rheumatoid arthritis. An extensive PubMed search is conducted to collect the relevant manuscripts. The metabolites are discussed in relation to rheumatoid arthritis. Subsequently, the metabolites are organized according to levels of system organization. In the last section an integrated pathway analysis of the metabolites conducted with Ingenuity Pathway Analysis software is presented. Literature search resulted in information about vitamins, eicosanoids, fatty acids, lipids, hormones and peptides. The metabolites could be related to metabolic processes, oxidative stress processes and inflammatory processes. Cell death, lipid metabolism and small molecule biochemistry were found by the pathway analysis to be the top functions, characterized by the metabolites arachidonic acid, ascorbic acid, beta-carotene, cholecalciferol, hydrocortisone, keratan sulfate, melatonin, palmitic acid and stearic acid. These nine metabolites are highly connected to a number of canonical pathways related to immune functions, the production of nitric oxygen and reactive oxygen species in macrophages and pathways involved in arthritis. This review indicates groups of metabolites that could be interesting for metabolomics studies related to rheumatoid arthritis. Circadian rhythms of metabolite levels are found to be important for understanding and treating rheumatoid arthritis. In addition, some key processes and pathways are found by integrating the metabolite data. This might offer new ideas for studies into the mechanism of and possible treatment options for rheumatoid arthritis.British Journal of Medicine and Medical Research. 07/2012; 2(3-2):469-483.
Article: Characterization of Rheumatoid Arthritis Subtypes Using Symptom Profiles, Clinical Chemistry and Metabolomics MeasurementsHerman A Van Wietmarschen, Weidong Dai, Anita J Van Der Kooij, Theo H Reijmers, Yan Schroë, Mei Wang, Zhiliang Xu, Xinchang Wang, Hongwei Kong, Guowang Xu, Thomas Hankemeier, Jacqueline J Meulman, Jan Van Der Greef[show abstract] [hide abstract]
ABSTRACT: Objective: The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA) patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies. Methods: In this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In addition, a Chinese medicine expert classified each RA patient as a Cold or Heat type according to Chinese medicine theory. Multivariate data analysis techniques are employed to detect and validate biochemical and symptom relationships with the classification. Results: The questionnaire items 'Red joints', 'Swollen joints', 'Warm joints' suggest differences in the level of inflammation between the groups although c-reactive protein (CRP) and rheumatoid factor (RHF) levels were equal. Multivariate analysis of the urine metabolomics data revealed that the levels of 11 acylcarnitines were lower in the Cold RA than in the Heat RA patients, suggesting differences in muscle breakdown. Additionally, higher dehydroepiandrosterone sulfate (DHEAS) levels in Heat patients compared to Cold patients were found suggesting that the Cold RA group has a more suppressed hypothalamic-pituitary-adrenal (HPA) axis function. Copyright: ß 2012 van Wietmarschen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: ThisPLoS ONE 09/2012; 7(9). · 4.09 Impact Factor
Article: Systems biology-based diagnostic principles as pillars of the bridge between Chinese and Western medicine.[show abstract] [hide abstract]
ABSTRACT: Innovative systems approaches to develop medicine and health care are emerging from the integration of Chinese and Western medicine strategies, philosophies and practices. The two medical systems are highly complementary as the reductionist aspects of Western medicine are favourable in acute disease situations and the holistic aspects of Chinese medicine offer more opportunities in chronic conditions and for prevention. In this article we argue that diagnosis plays a key role in building the bridge between Chinese and Western medicine. Recent advances in the study of health, healing, placebo effects and patient-physician interactions will be discussed pointing out the development of a system-based diagnosis. Especially, a system biology-based diagnosis can be used to capture phenotype information, leading towards a scientific basis for a more refined patient characterization, new diagnostic tools and personalized heath strategies. Subtyping of rheumatoid arthritis patients based on Chinese diagnostic principles is discussed as an example. New insights from this process of integrating Western and Chinese medicine will pave the way for a patient-centred health care ecosystem.Planta Medica 10/2010; 76(17):2036-47. · 2.15 Impact Factor
Article: Systems biology guided by Chinese medicine reveals new markers for sub-typing rheumatoid arthritis patients.Herman van Wietmarschen, Kailong Yuan, Cheng Lu, Peng Gao, Jiangshan Wang, Cheng Xiao, Xiaoping Yan, Mei Wang, Jan Schroën, Aiping Lu, Guowang Xu, Jan van der Greef[show abstract] [hide abstract]
ABSTRACT: Complex chronic diseases such as rheumatoid arthritis have become a major challenge in medicine and for the pharmaceutical industry. New impulses for drug development are needed. : A systems biology approach is explored to find subtypes of rheumatoid arthritis patients enabling a development towards more personalized medicine. Blood samples of 33 rheumatoid arthritis (RA) patients and 16 healthy volunteers were collected. The RA patients were diagnosed according to Chinese medicine (CM) theory and divided into 2 groups, the RA Heat and RA Cold group. CD4 T-cells were used for a total gene expression analysis. Metabolite profiles were measured in plasma using gas chromatography/mass spectrometry. Multivariate statistics was employed to find potential biomarkers for the RA Heat and RA Cold phenotype. A comprehensive biologic interpretation of the results is discussed. : The genomics and metabolomics analysis showed statistically relevant different gene expression and metabolite profiles between healthy controls and RA patients as well as between the RA Heat and RA Cold group. Differences were found in the regulation of apoptosis. In the RA Heat group caspase 8 activated apoptosis seems to be stimulated while in the RA Cold group apoptosis seems to be suppressed through the Nrf2 pathway. RA patients could be divided in 2 groups according to CM theory. Molecular differences between the RA Cold and RA Heat groups were found which suggest differences in apoptotic activity. Subgrouping of patients according to CM diagnosis has the potential to provide opportunities for better treatment outcomes by targeting Western or CM treatment to specific groups of patients.Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 10/2009; 15(7):330-7. · 1.19 Impact Factor
Medical biologist researching Chinese Medicine (CM) perspectives on the diagnosis and treatment of rheumatoid arthritis and diabetes. We use modern systems biology tools to identify sub-types of patients, guided by CM theory. We work towards the development of personalized treatment based on these sub-types. To support this, nonlinear data analysis strategies are developed to analyze symptom, clinical and metabolomics data.