Integrating Ultra-Weak Photon Emission Analysis in Mitochondrial Research.

Once regarded solely as the energy source of the cell, nowadays mitochondria are recognized to perform multiple essential functions in addition to energy production. Since the discovery of pathogenic mitochondrial DNA defects in the 1980s, research advances have revealed an increasing number of common human diseases, which share an underlying pathogenesis involving mitochondrial dysfunction. A major factor in this dysfunction is reactive oxygen species (ROS), which influence the mitochondrial-nuclear crosstalk and the link with the epigenome, an influence that provides explanations for pathogenic mechanisms. Regarding these mechanisms, we should take into account that mitochondria produce the majority of ultra-weak photon emission (UPE), an aspect that is often ignored - this type of emission may serve as assay for ROS, thus providing new opportunities for a non-invasive diagnosis of mitochondrial dysfunction. In this article, we overviewed three relevant areas of mitochondria-related research over the period 1960-2020: (a) respiration and energy production, (b) respiration-related production of free radicals and other ROS species, and (c) ultra-weak photon emission in relation to ROS and stress. First, we have outlined how these research areas initially developed independently of each other - following that, our review aims to show their stepwise integration during later stages of development. It is suggested that a further stimulation of research on UPE may have the potential to enhance the progress of modern mitochondrial research and its integration in medicine.

Integrated assessment of medicinal rhubarb by combination of delayed luminescence and HPLC fingerprint with emphasized on bioactivities based quality control.

BACKGROUND: To promote herbal medicine depends largely on its quality. Chromatographic fingerprint is a frequent approach for quality assessment of herbs however with challenges on robust and reproducibility. To develop rapid, cheap and comprehensive measurements as complementary tools for herbal quality control are still urgently needed. Moreover, biological activities are essential for herbal quality, and should be taken into consideration with emphasized in quality control. METHODS: In this research, HPLC fingerprint and delayed luminescence (DL, a rapid and systematic tool) were used to measure the rhubarb samples of multiple species. Statistics were explored to classify these rhubarb samples using data obtained from two analytic methods. In addition, DL properties were linked to specific chemical components which may reflect bioactivities of rhubarb using Spearman's rank correlation. Moreover, mice model was used to evaluate the cathartic effect between rhubarb samples stratifying by two analytic methods. RESULTS: We found that there was no significant difference of chemical fingerprints and DL signals among the different species of medicinal rhubarb. However, our results show a high similarity between HPLC fingerprint analysis and DL measurements in classification of these rhubarb samples into two sub-groups. In addition, the two sub-groups of rhubarb samples that may have different cathartic activities. CONCLUSION: This approach provides new leads for development of herbal quality assessment based on bioactivity. In conclusion, integrated assessment by measuring HPLC fingerprint and DL with emphasized on bioactivity may provide novel strategy for herbal quality control.

A comparative study of aged and contemporary Chinese herbal materials by using delayed luminescence technique.

BACKGROUND: Investigation of aged Chinese herbal materials will help us to understand their use and sources in ancient time and broaden the historical perspective of Chinese material medica. To reach this aim, the basic understanding of aged herbal materials, including physical and chemical characters, is of great importance. Delayed luminescence (DL) technique was developed as a rapid, direct, systemic, objective and sample loss-free tool to characterize the properties of Chinese herbal materials. In this study, we measured DL values in aged Chinese herbal materials that were transported from Asia to Europe during the 20th century and stored in Naturalis Biodiversity Center and the Utrecht University museum, and compared these with modern material of the same species. METHODS: A hyperbolic function was used to extract four properties from the DL curves of Chinese herbal material from 1900, the 1950s and recently harvested products. Statistical tools, including the Student's t test, One-way analysis of variance and Principal Component Analysis, were used to differentiate the DL properties of aged and contemporary collections of Glycyrrhiza spp. Curcuma aromatica Salisb., Zingiber officinale Roscoe, Alpinia officinarum Hance and Acorus calamus L. RESULTS: Our results showed that DL properties were significantly different between historical and contemporary Chinese herbal materials. Changes in DL values were species-dependent: the effects of storage time of DL properties were specific for each species. These outcomes help us not only in the identification of historical Chinese medicine products but also provides valuable data of the effect of storage time on herbal materials. CONCLUSION: The simple, direct, rapid, and inexpensive measurements offered by DL provide a novel tool to assess the taxonomic identity of Chinese and other herbal materials and assess the differences in chemical properties with increasing storage time. Our results contribute to the further development of novel digital tools for the quality control of herbal materials.

A Bridge of Light: Toward Chinese and Western Medicine Perspectives Through Ultraweak Photon Emissions.

The gap between Western medicine and traditional Chinese medicine (CM) is closely related to the diversity in culture, philosophy, and scientific developments. Although numerous studies have evaluated the efficacy of acupuncture, the gap in explanatory disease models has not been bridged so far. Developments in research of ultraweak photon emission (UPE) and organized dynamics of metabolism and its relationship with technological advances in metabolomics have created the conditions to bring the basics of the medicines of the West and East together which might open the avenue for a scientific dialogue. The paper discusses (1) the UPE in relation to Qi energy, meridians and acupuncture points in CM, (2) the biochemical explanation of photon emission of living systems in Western biomedicine, and (3) the progress in research on the large-scale organization and dynamics of the metabolic network including photon metabolism.

Characterization of ginsenoside extracts by delayed luminescence, high-performance liquid chromatography, and bioactivity tests.

Ginsenoside extracts are often used as raw materials for various pharmaceutical, cosmetic and food supplement products. Development of a direct, rapid, cheap, and comprehensive measurement tool for the quality assessment of ginsenoside extracts, and indeed all herbal extracts, is urgently needed. In addition, a bioactivity-based assessment should be linked with quality control. In this report, we try to develop a novel quality control tool using ginsenoside extracts as an example. High-performance liquid chromatography (HPLC) was used to detect nine principal ginsenosides in 11 batches of ginsenoside extracts. Delayed luminescence (DL) was used to analyze the same ginsenoside extract samples. DL measurements showed the same results in terms of differentiating 11 ginsenoside extract samples compared with chemical analysis, and DL properties could be closely linked to index ginsenosides in the quality control of ginsenoside extracts. Next, a zebrafish tail-fin amputation model was used to study differences in anti-inflammatory effect between the ginsenoside extract batches. The results indicate that both chemical analysis and DL measurements could partially reflect biological activity. Thus, DL may serve as a rapid, direct, sensitive, and systemic tool for studying the overall properties of ginsenoside extracts. Our proposal for linking bioactivities as a tool for evaluation of the quality of ginsenoside extracts opens a new direction for quality control.

Application of delayed luminescence method on measuring of the processing of Chinese herbal materials.

BACKGROUND: Based on the principle of tradition Chinese medicine, the processing refers to various techniques that alter the overall properties of herbal materials to meet the requirements of therapeutic applications. However, the standards of quality control and scientific standard operation protocol for processing manufacturing are largely unknown and there is a huge demand for the development of scientific tools for evaluating the quality during and after the processing. The key challenge in evidence-based medicine is to characterize the processing of herbal materials from system-based perspective. METHODS: Delayed luminescence (DL) as a rapid, direct, systemic tool was used to characterize the properties of raw and processed materials of Rehmanniae radix and Ginseng radix et rhizome. Hyperbolic function was used to extract four parameters from DL curves of herbal materials. Statistical tools, including one-way analysis of variance and principal component analysis, were used to differentiate raw and processed herbal materials. RESULTS: Our results showed DL properties were able to reliably identify raw and processed materials of Rehmanniae radix and Ginseng radix et rhizoma, respectively. In addition, the results indicated that after four cycles of processing for Rehmanniae radix, there was no much significant change in DL parameters which resembles the results obtained from chemical analyses (after five cycles) using 1HNMR and gas chromatography-mass spectrometry in previous studies. CONCLUSION: DL may serve as a fast, robust and sensitive tool for evaluating processing on herbs and may be used as part of a comprehensive platform for assessing the quality of herbal materials.

Protein Tethering for Folding Studies.

Optical tweezers allow the detection of unfolding and refolding transitions in individual proteins, and how interacting molecules such as chaperones affect these transitions. Typical methods that tether individual proteins are based on cysteine chemistry, which is less suitable for proteins with essential cysteines. Here we describe a cysteine-independent tethering protocol that can be performed in situ.

Spontaneous ultra-weak photon emission in correlation to inflammatory metabolism and oxidative stress in a mouse model of collagen-induced arthritis.

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 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.

Measuring ultra-weak photon emission as a non-invasive diagnostic tool for detecting early-stage type 2 diabetes: A step toward personalized medicine.

The global prevalence of type 2 diabetes is estimated to reach 4.4% by 2030, placing a significant burden on our healthcare system. Therefore, the ability to identify patients in early stages of the disease is essential for both prevention and effective management, and diagnostic methods based on traditional Chinese medicine (TCM) may be suitable for identifying patients with early-stage type 2 diabetes. Here, a panel of three physicians trained in TCM classified 44 pre-diabetic subjects into three syndrome subtypes using TCM-based diagnostics. In addition, ultra-weak photon emission (UPE) was measured at four anatomical sites in each subject. Ten properties encompassing 40 parameters were then extracted from the UPE time series. Statistical analyses, including multinomial logistic regression, were performed using the results of each parameter measured at the four sites. Sixteen UPE parameters were then selected and used to discriminate between the three subtypes of pre-diabetic subjects. Next, Spearman's correlation coefficient was used to quantify the correlation between the 16 UPE parameters and the TCM-based diagnoses. The resulting correlation networks accurately reflected the differences between the three syndrome subtypes. These results suggest that UPE is a suitable tool for detecting subtypes in early-stage type 2 diabetes. In addition, our results provide evidence that TCM may represent an important step toward personalized medicine.

Crossing the Boundaries of Our Current Healthcare System by Integrating Ultra-Weak Photon Emissions with Metabolomics.

The current healthcare system is hampered by a reductionist approach in which diagnostics and interventions focus on a specific target, resulting in medicines that center on generic, static phenomena while excluding inherent dynamic nature of biological processes, let alone psychosocial parameters. In this essay, we present some limitations of the current healthcare system and introduce the novel and potential approach of combining ultra-weak photon emission (UPE) with metabolomics technology in order to provide a dynamic readout of higher organizational systems. We argue that the combination of metabolomics and UPE can bring a new, broader, view of health state and can potentially help to shift healthcare toward more personalized approach that improves patient well-being.

Ultra-weak photon emission of hands in aging prediction.

Aging has been one of the several topics intensely investigated during recent decades. More scientists have been scrutinizing mechanisms behind the human aging process. Ultra-weak photon emission is known as one type of spontaneous photon emission that can be detected with a highly sensitive single photon counting photomultiplier tube (PMT) from the surface of human bodies. It may reflect the body's oxidative damage. Our aim was to examine whether ultra-weak photon emission from a human hand is able to predict one's chronological age. Sixty subjects were recruited and grouped by age. We examined four areas of each hand: palm side of fingers, palm side of hand, dorsum side of fingers, and dorsum side of hand. Left and right hand were measured synchronously with two independent PMTs. Mean strength and Fano factor values of photon counts were utilized to compare the UPE patterns of males and females of different age groups. Subsequently, we utilized UPE data from the most sensitive PMT to develop an age prediction model. We randomly picked 49 subjects to construct the model, whereas the remaining 11 subjects were utilized for validation. The results demonstrated that the model was a good regression compared to the observed values (Pearson's r=0.6, adjusted R square=0.4, p=9.4E-7, accuracy=49/60). Further analysis revealed that the average difference between the chronological age and predicted age was only 7.6±0.8years. It was concluded that this fast and non-invasive photon technology is sufficiently promising to be developed for the estimation of biological aging.

Effects of growth altitude on chemical constituents and delayed luminescence properties in medicinal rhubarb.

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 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.

A Chinese literature overview on ultra-weak photon emission as promising technology for studying system-based diagnostics.

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 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.

Delayed luminescence: an experimental protocol for Chinese herbal medicines.

In Chinese medicine, raw herbal materials are used in processed and unprocessed forms aiming to meet the different requirements of clinical practice. To assure the chemical quality and therapeutic properties of the herbs, fast and integrated systematic assays are required. So far, such assays have not been established. Delayed luminescence (DL) refers to a decaying long-term ultraweak photon emission after exposure to light. Its decay kinetics under certain conditions may be a sensitive indicator reflecting the internal structural and chemical/physiological state of a biological system. DL measurements have been used in many applications for quality control. However, relatively little research has been reported on dried plant material such as Chinese herbs. The objective of the present study is to establish a protocol for direct and rapid DL measurements of dried Chinese herbal materials, including the determination of the dependence on: (a) the optimal excitation time utilizing a white light source; (b) the optimal size of the grinded herbal particle; and (c) the humidity conditions before and during measurement. Results indicate that stable and reproducible curves of DL photon emission depend mainly on the water content of herbal materials. To investigate the application of the established DL measurement protocol, non-processed and processed Aconitum (Aconitum carmichaelii Debx.), wild and cultivated rhubarb (Rheum palmatum L.) and ginseng (Panax ginseng C.A.Mey) of different ages were measured using DL. The results suggest that DL technology is a potential tool for assessment of dried Chinese herb qualities. The results warrant a further exploration of this technique in relation to therapeutic properties of the herbs. Copyright © 2016 John Wiley & Sons, Ltd.

Physiological effects of homeopathic medicines in closed phials--a critical evaluation.

BACKGROUND: Phials containing high dilutions of homeopathic remedies are commonly utilized in diagnostic tools in combination with electro acupuncture measuring electrical conductivity of the skin. The present research aimed to elucidate the interaction of the homeopathic remedy and the human organism. METHOD: The study protocol included the transition of a healthy subject to a diseased state utilizing a sub-harmful dose of a toxin. Subsequently, the subject was exposed to a homeopathic or placebo remedy in a closed glass phial and electrical conductivity was measured in open as well as in blind trials. A total of 229 data were collected from open trials and 750 data from blind trials. RESULT: The experimental data showed that homoeopathic remedies in closed glass phials may influence the electrical skin conductivity. The results of the blind trials differed considerably from those of the open trials. The percentage of correctly identified (verum and placebo) phials in the open trials (85%) was statistically different from those in the blind trials (65%). In both types of trials, however, the difference between the sealed phials containing the homeopathic medicine and the placebo was statistically significant. The results of measurements are directly linked to the way in which the tester holds the electrode in one hand and the subject's finger in the other, while putting pressure on the electrode. CONCLUSION: It was concluded that the tester's muscle tone is the intermediary in unconsciously selecting which phial influenced him in his specific contact with the subject.

Non-monotonic dynamics and crosstalk in signaling pathways and their implications for pharmacology.

Currently, drug discovery approaches commonly assume a monotonic dose-response relationship. However, the assumption of monotonicity is increasingly being challenged. Here we show that for two simple interacting linear signaling pathways that carry two different signals with different physiological responses, a non-monotonic input-output relation can arise with simple network topologies including coherent and incoherent feed-forward loops. We show that non-monotonicity of the response functions has severe implications for pharmacological treatment. Fundamental constraints are imposed on the effectiveness and toxicity of any drug independent of its chemical nature and selectivity due to the specific network structure.

Trehalose facilitates DNA melting: a single-molecule optical tweezers study.

Using optical tweezers, here we show that the overstretching transition force of double-stranded DNA (dsDNA) is lowered significantly by the addition of the disaccharide trehalose as well as certain polyol osmolytes. This effect is found to depend linearly on the logarithm of the trehalose concentration. We propose an entropic driving mechanism for the experimentally observed destabilization of dsDNA that is rooted in the higher affinity of the DNA bases for trehalose than for water, which promotes base exposure and DNA melting. Molecular dynamics simulation reveals the direct interaction of trehalose with nucleobases. Experiments with other osmolytes confirm that the extent of dsDNA destabilization is governed by the ratio between polar and apolar fractions of an osmolyte.

Circuit topology of proteins and nucleic acids.

Folded biomolecules display a bewildering structural complexity and diversity. They have therefore been analyzed in terms of generic topological features. For instance, folded proteins may be knotted, have beta-strands arranged into a Greek-key motif, or display high contact order. In this perspective, we present a method to formally describe the topology of all folded linear chains and hence provide a general classification and analysis framework for a range of biomolecules. Moreover, by identifying the fundamental rules that intrachain contacts must obey, the method establishes the topological constraints of folded linear chains. We also briefly illustrate how this circuit topology notion can be applied to study the equivalence of folded chains, the engineering of artificial RNA structures and DNA origami, the topological structure of genomes, and the role of topology in protein folding.

Geographical and temporal distribution of basic research experiments in homeopathy.

The database HomBRex (Homeopathy Basic Research experiments) was established in 2002 to provide an overview of the basic research already done on homeopathy (http://www.carstens-stiftung.de/hombrex). By this means, it facilitates the exploration of the Similia Principle and the working mechanism of homeopathy. Since 2002, the total number of experiments listed has almost doubled. The current review reports the history of basic research in homeopathy as evidenced by publication dates and origin of publications. In July 2013, the database held 1868 entries. Most publications were reported from France (n = 267), followed by Germany (n = 246) and India (n = 237). In the last ten years, the number of publications from Brazil dramatically increased from n = 13 (before 2004) to n = 164 (compared to n = 251 published in France before 2004, and n = 16 between 2004 and 2013). The oldest database entry was from Germany (1832).

Ultraweak photon emission as a non-invasive health assessment: a systematic review.

We conducted a systematic review (SR) of the peer reviewed scientific literature on ultraweak photon emissions (UPE) from humans. The question was: Can ultraweak photon emissions from humans be used as a non-invasive health assessment? A systematic search was conducted across eight relevant databases: PubMed/MEDLINE, BIOSIS, CINAHL, PSYCHINFO, All of Cochrane EBM databases, GIDEON, DoD Biomedical Research, and clinicaltrials.gov from database inception to October 2011. Of the 1315 studies captured by the search strategy, 56 met the inclusion criteria, out of which 1 was a RCT, 27 were CCT, and 28 were observational and descriptive studies. There were no systematic reviews/meta-analyses that fit the inclusion criteria. In this report, the authors provide an assessment of the quality of the RCT included; describe the characteristics of all the included studies, the outcomes assessed, and the effectiveness of photon emission as a potential health assessment tool. This report demonstrates that the peer reviewed literature on UPE and human UPE measurement in particular is surprisingly large. Most of the human UPE literature is of good to high quality based on our systematic evaluation. However, an evaluation tool for systematically evaluating this type of "bio-evaluation" methodology is not currently available and would be worth developing. Publications in the peer reviewed literature over the last 50 years demonstrate that the use of "off-the-shelf" technologies and well described methodologies for the detection of human photon emissions are being used on a regular basis in medical and research settings. The overall quality of this literature is good and the use of this approach for determining inflammatory and oxidative states of patients indicate the growing use and value of this approach as both a medical and research tool.