Conclusions and perspectives
FUTURE PERSPECTIVES
In this thesis, we used metabolomics to bridge biochemistry with ultra-weak photon emission. Although we covered a relatively large number of biologically relevant endogenous metabolites in our studies, UPE can provide even more information regarding mechanistic and/or biochemical pathways if studied in association with an even wider range of metabolites. For example, the tricarboxylic acid (TCA) cycle may be an important pathway for future investigation, as this pathway is related to energy metabolism and is intimately connected with other metabolic pathways that were studied in this thesis, including amino acids and lipids.
With respect to pharmacology, UPE may open new avenues for exploration, particularly given the results obtained in this thesis in terms of the biochemical pathways that underlie UPE. Other enzymatic pathways related to ROS production should be investigated in future studies. The use of metabolomics as a tool for exploring the role of biophotons during drug modulation (the so-called “pharmaco-metabolomics” approach) can be a useful new approach in pharmacology studies. Given the ability to measure dynamic UPE profiles, spatiotemporal UPE data may be a powerful tool for use in detailed studies regarding personalized medicine.
In terms of models for studying UPE, other simplified models may be highly valuable. For example, zebrafish may be a good candidate model for measuring UPE due to the relatively
simplified organizational view of biological systems. In addition, the zebrafish model has several advantages over other animal models and human subject with respects to genetics, pharmacology, and drug development. Finally, zebrafish research is highly advanced, enabling the researcher to use non-invasive imaging techniques such as UPE, providing a clear advantage with respect to spatiotemporal UPE profiling.
The addition of UPE to observational clinical studies regarding certain diseases may also provide a valuable contribution to improving our understanding of biophoton-related processes. Given that increased UPE levels have been reported in some diseases9-11, and given the close correlation between UPE and ROS, it would be highly interesting to measure the UPE profile in various patient groups, including patients with cancer, mitochondrial dysfunction, chronic granulomatous disease, and/or atherosclerosis. In the context of diagnostics, UPE may serve as a useful tool for screening many ROS-related diseases. In this thesis, we focused on measuring the correlation between the UPE profile and the metabolites that change significantly at four time points measured over the span of 2.5 hours. Nevertheless, several questions remain, and other strategies, including the development of computational models, may reveal the power of using UPE to predict specific mechanisms. Another approach that may increase the value of the biochemical perspective is to combine metabolomics information with other omics data (e.g., proteomics and genomics) in the computational models. UPE is therefore likely to provide holistic information regarding the biochemical processes, as well as specific information regarding the underlying pathways. Thanks to recent studies, the role of UPE is now well understood, and a growing body of evidence suggests that UPE plays an essential role in biological processes12. This valuable feature of UPE is gaining more attention, and the emerging view of light as a signaling messenger may provide a robust tool for detecting new phenomena, ultimately opening new avenues for studying personalized health from a holistic perspective. Photons of life might develop into a journey of discovery tackling fundamental unanswered questions in science. REFERENCES
1 Alvarez-Sanchez, B., Priego-Capote, F. & de Castro, M. D. L. Metabolomics analysis I. Selection of biological samples and practical aspects preceding sample preparation. Trac-Trend Anal Chem29, 111-119 (2010).
2 Zhang, A., Sun, H., Xu, H., Qiu, S. & Wang, X. Cell metabolomics. OMICS17, 495- 501 (2013).
3 Birkness, K. A. et al. An in vitro model of the leukocyte interactions associated with granuloma formation in Mycobacterium tuberculosis infection. Immunol Cell Biol85, 160-168 (2007).
Conclusions and perspectives
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4 Cheson, B. D., Christensen, R. L., Sperling, R., Kohler, B. E. & Babior, B. M. The origin of the chemiluminescence of phagocytosing granulocytes. J Clin Invest 58, 789-796 (1976).
5 van Wijk, E., van der Greef, J. & van Wijk, R. Photon count statistics in leukocyte cell dynamics. Journal of Physics: Conference Series 329, 12-21 (IOP Publishing, 2011). 6 Birtic, S. et al. Using spontaneous photon emission to image lipid oxidation patterns
in plant tissues. Plant J67, 1103-1115 (2011).
7 Prasad, A. & Pospisil, P. Linoleic Acid-Induced Ultra-Weak Photon Emission from Chlamydomonas reinhardtii as a Tool for Monitoring of Lipid Peroxidation in the Cell Membranes. Plos One6, e22345 (2011).
8 Rastogi, A. & Pospisil, P. Ultra-weak photon emission as a non-invasive tool for the measurement of oxidative stress induced by UVA radiation in Arabidopsis thaliana. J
Photochem Photobiol B123, 59-64 (2013).
9 Kim, H. W. et al. Spontaneous photon emission and delayed luminescence of two types of human lung cancer tissues: adenocarcinoma and squamous cell carcinoma.
Cancer Lett229, 283-289 (2005).
10 Kim, J. et al. Measurements of spontaneous ultraweak photon emission and delayed luminescence from human cancer tissues. J Altern Complement Med 11, 879-884 (2005).
11 Kobayashi, M. et al. In vivo imaging of spontaneous ultraweak photon emission from a rat's brain correlated with cerebral energy metabolism and oxidative stress.
Neurosci Res34, 103-113 (1999).