A Proposed New Model To Explain The Role Of Low Dose Non-DNA Targeted Radiation Exposure in Chronic Fatigue And Immune Dysfunction Syndrome Part 2
Sep 07, 2023
3. Discussion
To assess and compare other potential CFIDS models to the systems model presented herein, we first performed numerous searches, in Pubmed, using the following query terms—Chronic Fatigue and Immune Dysfunction Syndrome disease model, Chronic Fatigue Syndrome disease model, as well as Myalgic Encephalomyelitis disease model. In addition, we reviewed several well-known research-based books on the subject as well as past issues of the Journal of Chronic Fatigue Syndrome [101–103]. We intended to examine the literature for any human pre-existing hierarchical disease models that utilized an integrated macroscopic-microscopic approach for the creation of a potential CFIDS model.
Cistanche can act as an anti-fatigue and stamina enhancer, and experimental studies have shown that the decoction of Cistanche tubulosa could effectively protect the liver hepatocytes and endothelial cells damaged in weight-bearing swimming mice, upregulate the expression of NOS3, and promote hepatic glycogen synthesis, thus exerting anti-fatigue efficacy. Phenylethanoid glycoside-rich Cistanche tubulosa extract could significantly reduce the serum creatine kinase, lactate dehydrogenase, and lactate levels, and increase the hemoglobin (HB) and glucose levels in ICR mice, and this could play an anti-fatigue role by decreasing the muscle damage and delaying the lactic acid enrichment for energy storage in mice. Compound Cistanche Tubulosa Tablets significantly prolonged the weight-bearing swimming time, increased the hepatic glycogen reserve, and decreased the serum urea level after exercise in mice, showing its anti-fatigue effect. The decoction of Cistanchis can improve endurance and accelerate the elimination of fatigue in exercising mice, and can also reduce the elevation of serum creatine kinase after load exercise and keep the ultrastructure of skeletal muscle of mice normal after exercise, which indicates that it has the effects of enhancing physical strength and anti-fatigue. Cistanchis also significantly prolonged the survival time of nitrite-poisoned mice and enhanced the tolerance against hypoxia and fatigue.
Click on Over fatigue
【For more info:george.deng@wecistanche.com / WhatsApp:8613632399501】
One such model, created by Englebienne and DeMeirleir, discussed how different onset mechanisms and changes to the immune system could elicit several events and symptoms that would not spontaneously reverse [102]. In their model, the authors discuss the patient onset and/or predisposition factors, such as viral or bacterial infections, that negatively impact the immune system. These bring about various intracellular changes, such as altered apoptosis, that trigger various biological events, such as T-cell activation and cytokine storm, to ultimately lead to patient symptoms, such as pain and malaise.
From our literature search, we learned that most current CFIDS papers focused on identifying various diagnostic markers or discussed limited functional mechanisms associated with the disease. Given that CFIDS is considered to be a complex multisystem disease that appears to be heterogeneous as a result of its case definition, this has created a tremendous challenge for those researchers and clinicians alike who are left to study and subsequently treat the disease. However, we do believe that multiple patient cohorts may exist that satisfy the current CFIDS case definition and that our system model, which points to intimate involvement of melanoma in some patients, may ultimately prove to be a reflection of this. Furthermore, the consensus is that CFIDS is an immunological disease. In this paper, NK cell cytotoxicity, STAT1, and IFI16 are examples of this. Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. This may prove to be a critical crossroad, from an immunological standpoint, that requires much greater scientific effort to gain a true understanding and appreciation for this part of the disease process. As such, additional CFIDS patient research confirming and delineating these mechanisms may be in order, especially given the cancer patient mortality associated with melanoma outcomes in those patients whose detection is delayed. Melanoma’s propensity to metastasize makes early recognition and excision the most important factor in patient survival [104].
Since our system’s model is based on internal radiation exposure, several additional important comments should be taken into consideration. The National Research Council publication Health Effects of Exposure to Low Levels of Ionizing Radiation (BEIR V) states that “the skin has a higher susceptibility to radiation carcinogenesis than has generally been suspected” and, while proposing risk estimates for both basal cell and squamous cell carcinomas, does not mention melanoma [105].
An extensive review of melanoma and ionizing radiation was previously generated by Fink and Bates [106]. Here, the authors examined data from the Canadian Radiation Dose Registry, nuclear industry workers, subjects near nuclear test blasts, survivors of the atomic bombings of Japan, airline pilots and cabin attendants, recipients of medical radiation, and radiological technicians. The authors provided evidence for elevated risks for melanoma related to exposure to ionizing radiation. The 2017 Swiss government-based paper on radon exposure and melanoma, mentioned earlier, is in line with the 2005 paper by Fink and Bates on ionizing radiation exposure and increased melanoma risk. Furthermore, in a large 29,000+ human study of the effects of external radiation exposure on the mortality of French nuclear workers, among the twenty-one main cancer sites studied, a statistically significant cancer excess was observed only for skin melanoma [107].
Given the possible elevated risk for CFIDS patients to develop melanoma, we suggest the following clinical testing be considered. The first would be to utilize increased skin cancer screenings to improve active surveillance for potential dermatological skin changes in CFIDS patients. Any skin changes should be closely monitored to minimize long-term patient risk for melanoma. Secondly, to utilize the quantitative measurement of Eosinophil Cationic Protein (ECP) in human serum. This test is commercially available in the United States, and it may be available elsewhere. As mentioned previously, ECP is significantly elevated in CFIDS patients, and since it is a prognostic serum marker for melanoma, we encourage its use in these patients. Furthermore, obtaining a baseline measurement in a patient may prove to be a useful addition to a clinician’s diagnostic arsenal as it may assist in monitoring potential disease progression. As such, we firmly believe that these clinical tests may prove to be helpful in CFIDS patients who may be at potential risk for melanoma development.
The fact that the mechanisms described here involve continuous exposure to stress such as UVA radiation, biophotons, radionuclides, etc. suggests that an accelerated aging process, rather than an increased cancer risk, may be associated with CFIDS. Conversely, some literature data suggest that to potentially lead to a cancer progression, the exposure to stress should be repeated, chronic but with some periods of non-stress to permit cells to propagate errors and to bypass cell cycle arrests. In this regard, research at the CDC has identified premature telomere attrition in CFIDS patients [108]. The telomere length was shorter, and this translated to roughly 10+ years of additional aging in patients. Telomeres, which act as molecular caps at the ends of chromosomes to protect humans against aging and cancer, have been shown to have a surprising inability to protect themselves against UV radiation [109–111]. Thus, the chromosome’s guardians are susceptible to UV radiation effects, and the damage to telomeres was not repaired. As telomeres shorten, cells age, deteriorate, and eventually die. As cells divide over a lifetime, telomeres tend to wear down, and the resulting chromosomal instability can potentially lead to an increased cancer risk. Increasing evidence has been gathered that shows that the long-term effects of radiation exposure are due to oxidative changes leading to the continuous accumulation of DNA damage in the progeny of both irradiated and non-irradiated bystander cells and that telomeres are a key player in radiation-induced carcinogenesis [112]. According to a more recent paper by Samuel, ergothioneine has been shown to mitigate telomere shortening under oxidative stress conditions [113]. As such, we suggest additional research, both at the bench and in a clinical setting, to determine the potential utility of the use of L-ergothioneine as a treatment option for CFIDS patients.
Overall, the mechanism that we have proposed here integrates UVA radiation, biophotons, and radionuclides, whose molecular responses obey different kinetics according to the specific DNA damage they induce. For example, the repair of DNA base damage induced by UVA radiation is expected to be faster than that of DNA strand breaks induced by radionuclides. Our question going forward is: How do we best integrate these features into the model as well as the clinical picture in CFIDS patients?
4. Conclusions
This paper presents a new model using systems biology to integrate information from the literature across several systems and several levels of organization to produce a new fundamental model to explain CFIDS etiology, which potentially connects to melanoma development. Through continuous internal radiation exposure caused by internal emitters of ionizing radiation, UV biophotons are liberated. While the model focuses on ionizing radiation due to ingested or inhaled radioactive particles as an example of a possible causative factor for CFIDS, this methodology could also apply to other trigger stressors where elevation of ROS is involved in the disease process. The benefits of this systems model approach are that it helps identify key points in the mechanism where targeted treatment interventions could be possible. Some of these, such as the use of melanin and L-ergothioneine, are actively being researched by our group [16,114–118].
Author Contributions: A.C.: conceptualization, writing, development of figure; C.S.: Conceptualisation, writing; C.M.: conceptualization, writing drafting figure. All authors have read and agreed to the published version of the manuscript.
Funding: The research received no external funding.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
References
1. Bell, D.S. The Disease of a Thousand Names: CFIDS—CHRONIC Fatigue/Immune Dysfunction Syndrome; Pollard Publications: La Jolla, CA, USA, 1991.
2. Loganovsky, K. Chronic Fatigue Syndrome as a Characteristic Aftermath of Radioecological Catastrophe. Int. J. Psychophysiol. 2000, 35, 69.
3. Loganovsky, K.N. Chronic Fatigue Syndrome in the Chornobyl Accident Consequences Liquidators. Int. J. Radiat. Med. 2001, 3, 76.
4. Loganovsky, K. Do Low Doses of Ionizing Radiation Affect the Human Brain? Data Sci. J. 2009, 8, 13–35. [CrossRef]
5. Tang, F.R.; Loganovsky, K. Low Dose or Low Dose Rate Ionizing Radiation-Induced Health Effect in the Human. J. Environ. Radioact. 2018, 192, 32–47. [CrossRef] [PubMed]
6. Bazyka, D.; Loganovsky, K.; Ilyenko, I.; Volovyk, S.; Perchuk, I.; Pleskach, O.; Nechayev, S. Psychophysiological, Neuroimmune and Gene Expression Changes in Chronic Fatigue Syndrome after Low-Dose Radiation Exposure. Int. J. Psychophysiol. 2010, 77, 340. [CrossRef]
7. Loganovsky, K.N. Vegetative-Vascular Dystonia and Osteoalgetic Syndrome or Chronic Fatigue Syndrome as a Characteristic After-Effect of Radioecological Disaster. J. Chronic Fatigue Syndr. 2000, 7, 3–16. [CrossRef]
8. National CFIDS Foundation. National CFIDS Foundation (NCF) Announces Link between Chronic Fatigue Syndrome and Low-Level Radiation Exposure; PR Newswire: Chicago, IL, USA, 2010.
9. National CFIDS Foundation. National CFIDS Foundation's Research Finds Chromosome Damage in Patients Diagnosed with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis; PR Newswire: Chicago, IL, USA, 2014.
10. Heng, H.H.Q.; Liu, G.; Stevens, J.B.; Abdallah, B.Y.; Horne, S.D.; Ye, K.J.; Bremer, S.W.; Chowdhury, S.K.; Ye, C.J. Karyotype Heterogeneity and Unclassified Chromosomal Abnormalities. Cytogenet. Genome Res. 2013, 139, 144–157. [CrossRef]
11. Boubriak, I.; Akimkina, T.; Polischuk, V.; Dmitriev, A.; Mccready, S.; Grodzinsky, D. Long-term effects of Chornobyl contamination on DNA repair function and plant resistance to biotic and abiotic stress factors. TSitologiia Genet. 2016, 50, 34–59. [CrossRef]
12. Yushkova, E. Genetic mechanisms of formation of radiation-induced instability of the genome and its transgenerational effects in the descendants of chronically irradiated individuals of Drosophila melanogaster. Radiat. Environ. Biophys. 2020, 59, 221–236. [CrossRef]
13. Ahmad, S.B.; McNeill, F.E.; Byun, S.H.; Prestwich, W.V.; Seymour, C.; Mothersill, C.E. Ion Beam Induced Luminescence; Relevance to Radiation-Induced Bystander Effects. Nucl. Instrum. Methods Phys. Res. Sect. B Beam Interact. Mater. At. 2012, 288, 81–88. [CrossRef]
14. Ahmad, S.B.; McNeill, F.E.; Byun, S.H.; Prestwich, W.V.; Mothersill, C.; Seymour, C.; Armstrong, A.; Fernandez, C. Ultra-Violet Light Emission from HPV-G Cells Irradiated with Low Let Radiation From (90)Y; Consequences for Radiation-Induced Bystander Effects. Dose-Response 2013, 11, 498–516. [CrossRef]
15. Mothersill, C.; Le, M.; Rusin, A.; Seymour, C. Biophotons in Radiobiology: Inhibitors, Communicators and Reactors. Radiat. Prot. Dosim. 2019, 183, 136–141. [CrossRef]
16. Le, M.; McNeill, F.E.; Seymour, C.; Rainbow, A.J.; Mothersill, C.E. An observed effect of ultraviolet radiation emitted from beta-irradiated HaCaT cells upon non-beta-irradiated bystander cells. Radiat. Res. 2015, 183, 279–290. [CrossRef] [PubMed]
17. Le, M.; Mothersill, C.E.; Seymour, C.B.; Ahmad, S.B.; Armstrong, A.; Rainbow, A.J.; McNeill, F.E. Factors affecting ultraviolet-A photon emission from β-irradiated human keratinocyte cells. Phys. Med. Biol. 2015, 60, 6371–6389. [CrossRef] [PubMed]
18. Le, M.; Mothersill, C.E.; Seymour, C.B.; Rainbow, A.J.; McNeill, F.E. An Observed Effect of p53 Status on the Bystander Response to Radiation-Induced Cellular Photon Emission. Radiat. Res. 2017, 9187, 169–185. [CrossRef] [PubMed]
19. Cohen, J.; Vo, N.T.K.; Chettle, D.R.; McNeill, F.E.; Seymour, C.B.; Mothersill, C.E. Quantifying Biophoton Emissions From Human Cells Directly Exposed to Low-Dose Gamma Radiation. Dose-Response 2020, 18, 1559325820926763. [CrossRef] [PubMed]
20. Le, M.; McNeill, F.E.; Seymour, C.B.; Rusin, A.; Diamond, K.; Rainbow, A.J.; Murphy, J.; Mothersill, C.E. Modulation of oxidative phosphorylation (OXPHOS) by radiation-induced biophotons. Environ. Res. 2018, 163, 80–87. [CrossRef]
21. The Water in You: Water and the Human Body. Water Science School. 2019. Available online: https://www.usgs.gov/specialtopics/water-science-school/science/water-you-water-and-human-body (accessed on 13 March 2023).
22. Le Caer, S. Radiolysis: Influence of Oxide Surfaces on H2 Production under Ionizing Radiation. Water 2011, 3, 235–253. [CrossRef]
23. Richards, R.S.; Roberts, T.K.; McGregor, N.R.; Dunstan, R.H.; Butt, H.L. Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep. 2000, 5, 35–41. [CrossRef]
24. Clutton, S.M.; Townsend, K.M.; Walker, C.; Ansell, J.D.; Wright, E.G. Radiation-induced genomic instability and persisting oxidative stress in primary bone marrow cultures. Carcinogenesis 1996, 17, 1633–1639. [CrossRef]
25. O’Reilly, J.P.; Mothersill, C. Comparative effects of UV A and UV B on clonogenic survival and delayed cell death in skin cell lines from humans and fish. Int. J. Radiat. Biol. 1997, 72, 111–119. [PubMed]
26. Ridley, A.J.; Whiteside, J.R.; McMillan, T.J.; Allinson, S.L. Cellular and sub-cellular responses to UVA about carcinogenesis. Int. J. Radiat. Biol. 2009, 85, 177–195. [CrossRef] [PubMed]
27. Whiteside, J.R.; McMillan, T.J. A bystander effect is induced in human cells treated with UVA radiation but not UVB radiation. Radiat. Res. 2009, 171, 204–211. [CrossRef] [PubMed]
28. Jella, K.K.; Moriarty, R.; McClean, B.; Byrne, H.J.; Lyng, F.M. Reactive oxygen species and nitric oxide signaling in bystander cells. PLoS ONE 2018, 13, e0195371. [CrossRef] [PubMed]
29. NIH News in Health. Sun and Skin: The Dark Side of Sun Exposure; NIH News in Health: Bethesda, MD, USA, 2014.
30. Jin, S.G.; Padron, F.; Pfeifer, G.P. UVA Radiation, DNA Damage, and Melanoma. ACS Omega 2022, 7, 32936–32948. [CrossRef]
31. Bernerd, F.; Passeron, T.; Castiel, I.; Marionnet, C. The Damaging Effects of Long UVA (UVA1) Rays: A Major Challenge to Preserve Skin Health and Integrity. Int. J. Mol. Sci. 2022, 23, 8243. [CrossRef]
32. Khan, A.Q.; Travers, J.B.; Kemp, M.G. Roles of UVA Radiation and DNA Damage Responses in Melanoma Pathogenesis. Environ. Mol. Mutagen. 2018, 59, 438–460. [CrossRef]
33. Kapp, F.G.; Perlin, J.R.; Hagedorn, E.J.; Gansner, J.M.; Schwarz, D.E.; O’Connell, L.A.; Johnson, N.S.; Amemiya, C.; Fisher, D.E.; Wolfle, U.; et al. Protection from UV light is an evolutionarily conserved feature of the hematopoietic niche. Nature 2018, 558, 445–448. [CrossRef]
34. Kamran, N.; Li, Y.; Sierra, M.; Alghamri, M.S.; Kadiyala, P.; Appelman, H.D.; Edwards, M.; Lowenstein, P.R.; Castro, M.G. Melanoma induced immunosuppression is mediated by hematopoietic dysregulation. Oncoimmunology 2017, 7, e1408750. [CrossRef]
35. Decker, J.M. Immunology: B-Cell Development. Department of Veterinary Science and Microbiology, University of Arizona. Available online: http://microvet.arizona.edu/Courses/MIC419/Tutorials/Bcelldevelopment.html (accessed on 13 March 2023).
36. Chang, C.M.; Warren, J.L.; Engels, E.A. Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults. Cancer 2012, 118, 5929–5936. [CrossRef]
37. Johnson, H. Osler’s Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic; Crown Publishers: New York, NY, USA, 1996.
38. Lundell, K.; Qazi, S.; Eddy, L.; Uckun, F.M. Clinical activity of folinic acid in patients with chronic fatigue syndrome. Arzneimittelforschung 2006, 56, 399–404. [CrossRef] [PubMed]
39. Turick, C.E.; Ekechukwu, A.A.; Milliken, C.E.; Casadevall, A.; Dadachova, E. Gamma radiation interacts with melanin to alter its oxidation-reduction potential and results in electric current production. Bioelectrochemistry 2011, 82, 69–73. [CrossRef] [PubMed]
40. Vienneau, D.; de Hoogh, K.; Hauri, D.; Vicedo-Cabrera, A.M.; Schindler, C.; Huss, A.; Roosli, M.; SNC Study Group. Effects of Radon and UV Exposure on Skin Cancer Mortality in Switzerland. Environ. Health Perspect. 2017, 125, 067009.
41. Knox, K.K.; Carrigan, D.R. Potential Role of STAT1 in the Pathogenesis of Chronic Fatigue Syndrome; Institute for Viral Pathogenesis: Madison, WI, USA, 2003.
42. Knox, K.K.; Cocchetto, A.; Jordan, E.; Leech, D.; Carrigan, D.R. Deficiency in the Expression of STAT1 Protein in a Subpopulation of Patients with Chronic Fatigue Syndrome (CFS). In Proceedings of the Seventh International AACFS Conference on Chronic Fatigue Syndrome, Fibromyalgia and other Related Illnesses, Madison, WI, USA, 8–10 October 2004.
43. Maziere, C.; Dantin, F.; Dubois, F.; Santos, R.; Maziere, J. Biphasic Effect of UVA Radiation on Stat1 Activity and Tyrosine Phosphorylation in Cultured Human Keratinocytes. Free Radic. Bio. Med. 2000, 28, 1430–1437. [CrossRef]
44. Aragane, Y.; Kulms, D.; Luger, T.A.; Schwarz, T. Down-regulation of interferon gamma-activated STAT1 by UV light. Proc. Natl. Acad. Sci. USA 1997, 94, 11490–11495. [CrossRef]
45. Kwon, T.R.; Oh, C.T.; Choi, E.J.; Kim, S.R.; Jang, Y.J.; Ko, E.J.; Suh, D.; Yoo, K.H.; Kim, B.J. Ultraviolet light-emitting-diode irradiation inhibits TNF-α and IFN-γ-induced expression of ICAM-1 and STAT1 phosphorylation in human keratinocytes. Lasers Surg. Med. 2015, 47, 824–832. [CrossRef]
46. Eschrich, S.; Zhang, H.; Zhao, H.; Boulware, D.; Lee, J.H.; Bloom, G.; Torres-Roca, J.F. Systems biology modeling of the radiation sensitivity network: A biomarker discovery platform. Int. J. Radiat. Oncol. Biol. Phys. 2009, 75, 497–505. [CrossRef]
47. Huang, L.; Chen, J.; Zhao, Y.; Gu, L.; Shao, X.; Li, J.; Xu, Y.; Liu, Z.; Xu, Q. Key candidate genes of STAT1 and CXCL10 in melanoma identified by integrated bioinformatical analysis. IUBMB Life 2019, 71, 1634–1644. [CrossRef]
48. Friedman, M.A.; Fernandez, M.; Backer, L.C.; Dickey, R.W.; Bernstein, J.; Schrank, K.; Kibler, S.; Wendy, S.; Gribble, M.O.; Bienfang, P.; et al. An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management. Mar. Drugs 2017, 15, 72. [CrossRef]
49. Pearn, J.H. Chronic fatigue syndrome: Chronic ciguatera poisoning as a differential diagnosis. Med. J. Aust. 1997, 166, 309–310. [CrossRef]
50. Lombet, A.; Bidard, J.N.; Lazdunski, M. Ciguatoxin and brevetoxins share a common receptor site on the neuronal voltage-dependent Na+ channel. FEBS Lett. 1987, 219, 355–359. [CrossRef] [PubMed]
51. Rook, M.B.; Evers, M.M.; Vos, M.A.; Bierhuizen, M.F.A. Biology of cardiac sodium channel Nav1. 5 expression. Cardiovasc. Res. 2012, 93, 12–23. [CrossRef] [PubMed]
52. Hokama, Y.; John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. Personal communication, 2008.
53. Hokama, Y.; Uto, G.A.; Palafox, N.A.; Enlander, D.; Jordan, E.; Cocchetto, A. Chronic phase lipids in sera of chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), hepatitis B, and cancer with antigenic epitope resembling ciguatoxin, as assessed with Mab-CTX. J. Clin. Lab. Anal. 2003, 17, 132–139. [CrossRef] [PubMed]
54. Hokama, Y.; Empey-Campora, C.; Hara, C.; Higa, N.; Siu, N.; Lau, R.; Kuribayashi, T.; Yabusaki, K. Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins. J. Clin. Lab. Anal. 2008, 22, 99–105. [CrossRef] [PubMed]
55. Wang, G.K.; Wang, S.Y. Modifications of human cardiac sodium channel gating by UVA light. J. Membr. Biol. 2002, 189, 153–165. [CrossRef]
56. Xie, A.; Gallant, B.; Guo, H.; Gonzalez, A.; Clark, M.; Madigan, A.; Feng, F.; Chen, H.D.; Cui, Y.; Dudley, S.C., Jr.; et al. Functional cardiac Na + channels are expressed in human melanoma cells. Onco. Lett. 2018, 16, 1689–1695. [CrossRef] [PubMed]
57. Djamgoz, M.B.A.; Fraser, S.P.; Brackenbury, W.J. In Vivo Evidence for Voltage-Gated Sodium Channel Expression in Carcinomas and Potentiation of Metastasis. Cancers 2019, 11, 1675. [CrossRef]
58. Roelant, C.H.S.; DeMeirleir, K.L. Methods and means for diagnosing and/or treating a fatiguing illness. World Patent WO2019012159, 16 July 2018.
59. Hou, G.; Xu, B.; Bi, Y.; Wu, C.; Ru, B.; Sun, B.; Bai, X. Recent advances in research on aspartate β-hydroxylase (ASPH) in pancreatic cancer: A brief update. Bosn. J. Basic Med. Sci. 2018, 18, 297–304. [CrossRef]
60. Zheng, W.; Wang, X.; Hu, J.; Bai, B.; Zhu, H. Diverse molecular functions of aspartate β-hydroxylase in cancer (Review). Oncol. Rep. 2020, 44, 2364–2372. [CrossRef]
61. Wands, J.R.; De La Monte, S.; Aihara, A.; Olsen, M.J.; Thomas, J.M. Inhibitors of beta-hydroxylase for treatment of cancer. U.S. Patent Application 20200361925, 2 June 2020.
62. Radrezza, S.; Carini, M.; Baron, G.; Aldini, G.; Negre-Salvayre, A.; D’Amat, A. Study of Carnosine’s effect on nude mice skin to prevent UV-A damage. Free Radic. Biol. Med. 2021, 173, 97–103. [CrossRef]
63. Miller, J.S.; McCullar, V.; Punzel, M.; Lemischka, I.R.; Moore, K.A. Single adult human CD34(+)/Lin-/CD38(-) progenitors give rise to natural killer cells, B-lineage cells, dendritic cells, and myeloid cells. Blood 1999, 93, 96–106. [CrossRef]
64. Brenu, E.W.; Hardcastle, S.L.; Atkinson, G.M.; van Driel, M.L.; Kreijkamp-Kaspers, S.; Ashton, K.J.; Staines, D.R.; MarshallGradisnik, S.M. Natural killer cells in patients with severe chronic fatigue syndrome. Auto Immun. Highlights 2013, 4, 69–80. [CrossRef] [PubMed]
65. Vokurkova, D.; Vavrova, J.; Sinkora, J.; Stoklasova, A.; Blaha, V.; Rezacova, M. Radiosensitivity of CD3-CD8+CD56+ NK cells. Radiat. Meas. 2010, 45, 1020–1023. [CrossRef]
66. Brenu, E.W.; Staines, D.R.; Baskurt, O.K.; Ashton, K.J.; Ramos, S.B.; Christy, R.M.; Marshall-Gradisnik, S.M. Immune and hemorheological changes in chronic fatigue syndrome. J. Transl. Med. 2010, 8, 1. [CrossRef] [PubMed]
67. Brenu, E.W.; van Driel, M.L.; Staines, D.R.; Ashton, K.J.; Ramos, S.B.; Keane, J.; Klimas, N.G.; Marshall-Gradisnik, S.M. Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J. Transl. Med. 2011, 9, 81. [CrossRef]
68. Brenu, E.W.; van Driel, M.L.; Staines, D.R.; Ashton, K.J.; Hardcastle, S.L.; Keane, J.; Tajouri, L.; Peterson, D.; Ramos, S.B.; Marshall-Gradisnik, S.M. Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis. J. Transl. Med. 2012, 10, 88. [CrossRef]
69. Hersey, P.; MacDonald, M.; Henderson, C.; Schibeci, S.; D’Alessandro, G.; Pryor, M.; Wilkinson, F.J. Suppression of natural killer cell activity in humans by radiation from solarium lamps depleted of UVB. J. Investig. Dermatol. 1988, 90, 305–310. [CrossRef]
70. Hersey, P.; Magrath, H.; Wilkinson, F. Development of an in vitro system for the analysis of ultraviolet radiation-induced suppression of natural killer cell activity. Photochem. Photobiol. 1993, 57, 279–284. [CrossRef]
71. de Jonge, K.; Ebering, A.; Nassiri, S.; Maby-El Hajjami, H.; Ouertatani-Sakouhi, H.; Baumgaertner, P.; Speiser, D.E. Circulating CD56 bright NK cells inversely correlate with survival of melanoma patients. Sci. Rep. 2019, 9, 4487. [CrossRef]
72. Simpson, L.O. The role of nondiscocytic erythrocytes in the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome. In The Clinical and Scientific Basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Hyde, B.M., Ed.; The Nightingale Research Foundation: Street Ottawa, ON, Canada, 1992; Volume 65, pp. 597–605.
73. Richards, R.S.; Wang, L.; Jelinek, H. Erythrocyte oxidative damage in chronic fatigue syndrome. Arch Med. Res. 2007, 38, 94–98. [CrossRef]
74. Saha, A.K.; Schmidt, B.R.; Wilhelmy, J.; Nguyen, V.; Abugherir, A.; Do, J.K.; Nemat-Gorgani, M.; Davis, R.W.; Ramasubramanian, A.K. Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome. Clin. Hemorheol. Microcirc. 2019, 71, 113–116. [CrossRef]
75. Kozlova, E.; Chernysh, A.; Sergunova, V.; Gudkova, O.; Manchenko, E.; Kozlov, A. Atomic force microscopy study of red blood cell membrane nanostructure during oxidation-reduction processes. J. Mol. Recognit. 2018, 31, e2724. [CrossRef] [PubMed]
76. Nguyen, C.B.; Alsøe, L.; Lindvall, J.M.; Sulheim, D.; Fagermoen, E.; Winger, A.; Kaarbø, M.; Nilsen, H.; Wyller, V.B. Whole blood gene expression in adolescent chronic fatigue syndrome: An exploratory cross-sectional study suggesting altered B cell differentiation and survival. J. Transl. Med. 2017, 15, 102. [CrossRef] [PubMed]
77. Sato, W.; Ono, H.; Matsutani, T.; Nakamura, M.; Shin, I.; Amano, K.; Suzuki, R.; Yamamura, T. Skewing of the B cell receptor repertoire in myalgic encephalomyelitis/chronic fatigue syndrome. Brain Behav. Immun. 2021, 95, 245–255. [CrossRef]
78. Costa, S.; Borgogna, C.; Mondini, M.; De Andrea, M.; Meroni, P.L.; Berti, E.; Gariglio, M.; Landolfo, S. Redistribution of the nuclear protein IFI16 into the cytoplasm of ultraviolet B-exposed keratinocytes as a mechanism of autoantigen processing. Br. J. Dermatol. 2011, 164, 282–290. [CrossRef] [PubMed]
79. Wang, H.; Xie, X.; Zhu, J.; Qi, S.; Xie, J. Comprehensive analysis identifies IFI16 as a novel signature associated with overall survival and immune infiltration of skin cutaneous melanoma. Cancer Cell Int. 2021, 21, 694. [CrossRef]
80. Dibble, J.J.; McGrath, S.J.; Ponting, C.P. Genetic risk factors of ME/CFS: A critical review. Hum. Mol. Genet. 2020, 29, R117–R124. [CrossRef]
81. Ji, S.M. Overexpression of SLC25A15 is involved in the proliferation of cutaneous melanoma and leads to poor prognosis. Med. Sci. (Paris) 2018, 34, 74–80. [CrossRef] [PubMed]
82. Boix, E.; Carreras, E.; Nikolovski, Z.; Cuchillo, C.M.; Nogues, M.V. Identification and characterization of human eosinophil cationic protein by an epitope-specific antibody. J. Leukoc. Biol. 2001, 69, 1027–1035. [CrossRef] [PubMed]
83. Conti, F.; Magrini, L.; Priori, R.; Valesini, G.; Bonini, S. Eosinophil cationic protein serum levels and allergy in chronic fatigue syndrome. Allergy 1996, 51, 124–127. [CrossRef]
84. Sorensen, B.; Streib, J.E.; Strand, M.; Make, B.; Giclas, P.C.; Fleshner, M.; Jones, J.F. Complement activation in a model of chronic fatigue syndrome. J. Allergy Clin. Immunol. 2003, 112, 397–403. [CrossRef] [PubMed]
85. Kruckel, A.; Moreira, A.; Frohlich, W.; Schuler, G.; Heinzerling, L. Eosinophil-cationic protein—A novel liquid prognostic biomarker in melanoma. BMC Cancer 2019, 19, 207. [CrossRef] [PubMed]
86. Mueller, C.; Lin, J.C.; Sheriff, S.; Maudsley, A.A.; Younger, J.W. Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: Assessment with whole-brain magnetic resonance spectroscopy. Brain Imaging Behav. 2020, 14, 562–572. [CrossRef]
87. Stanculescu, D.; Sepulveda, N.; Lim, C.L.; Bergquist, J. Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front. Neurol. 2021, 12, 789784. [CrossRef] [PubMed]
88. Sasso, E.M.; Muraki, K.; Eaton-Fitch, N.; Smith, P.; Lesslar, O.L.; Deed, G.; Marshall-Gradisnik, S. Transient Receptor Potential Melastatin 3 Dysfunction in Post COVID-19 Condition and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Mol. Med. 2022, 28, 98. [CrossRef] [PubMed]
89. Vriens, J.; Owsianik, G.; Hofmann, T.; Philipp, S.E.; Stab, J.; Chen, X.; Benoit, M.; Xue, F.; Janssens, A.; Kerselaers, S.; et al. TRPM3 is a Nociceptor Channel Involved in the Detection of Noxious Heat. Neuron 2011, 70, 482–494. [CrossRef]
90. Caterina, M.J. Transient Receptor Potential Ion Channels as Participants in Thermosensation and Thermoregulation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007, 292, R64–R76. [CrossRef] [PubMed]
91. Okabe, T.; Fujimura, T.; Okajima, J.; Kambayashi, Y.; Aiba, S.; Maruyama, S. First-in-human clinical study of a novel technique to diagnose malignant melanoma via thermal conductivity measurements. Sci. Rep. 2019, 9, 3853. [CrossRef]
92. Wrotek, S.; Brycht, L.; Wrotek, W.; Kozak, W. Fever as a factor contributing to long-term survival in a patient with metastatic melanoma: A case report. Complement. Ther. Med. 2018, 38, 7–10. [CrossRef]
93. Le, M.; Fernandez-Palomo, C.; McNeill, F.E.; Seymour, C.B.; Rainbow, A.J.; Mothersill, C.E. Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect. PLoS ONE 2017, 12, e0173685. [CrossRef]
94. Blauensteiner, J.; Bertinat, R.; Leon, L.E.; Riederer, M.; Sepulveda, N.; Westermeier, F. Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients. Sci. Rep. 2021, 11, 10604. [CrossRef] [PubMed]
95. Brenu, E.W.; Ashton, K.J.; van Driel, M.; Staines, D.R.; Peterson, D.; Atkinson, G.M.; Marshall-Gradisnik, S.M. Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J. Affect Discord 2012, 141, 261–269. [CrossRef] [PubMed]
96. Xu, S.; Ding, N.; Pei, H.; Hu, W.; Wei, W.; Zhang, X.; Zhou, G.; Wang, J. MiR-21 is involved in radiation-induced bystander effects. RNA Biol. 2014, 11, 1161–1170. [CrossRef] [PubMed]
97. Xu, S.; Wang, J.; Ding, N.; Hu, W.; Zhang, X.; Wang, B.; Hua, J.; Wei, W.; Zhu, Q. Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect. RNA Biol. 2015, 12, 1355–1363. [CrossRef]
98. Melnik, B.C.; John, S.M.; Carrera-Bastos, P.; Schmitz, G. MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors. Cancers 2020, 12, 2111. [CrossRef]
99. Lai, J.Y.; Luo, J.; O’Connor, C.; Jing, X.; Nair, V.; Ju, W.; Randolph, A.; Ben-Dov, I.Z.; Matar, R.N.; Briskin, D.; et al. MicroRNA-21 in glomerular injury. J. Am. Soc. 2015, 26, 805–816. [CrossRef]
100. Zhang, L.; He, S.; Yang, F.; Yu, H.; Xie, W.; Dai, Q.; Zhang, D.; Liu, X.; Zhou, S.; Zhang, K. Hyperoside ameliorates glomerulosclerosis in diabetic nephropathy by downregulating miR-21. Can. J. Physiol. Pharmacol. 2016, 94, 1249–1256. [CrossRef]
101. Hyde, B.M.; Goldstein, J.A.; Levine, P.H. The Nightingale Research Foundation Review of the Clinical and Scientific Basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Nightingale Research Foundation: Ottawa, ON, Canada, 1992.
102. Englebienne, P.; DeMeirleir, K. Chronic Fatigue Syndrome: A Biological Approach; CRC Press: Boca Raton, FL, USA, 2002.
103. Journal of Chronic Fatigue Syndrome. 1995:1(1)–2007:14(4). Taylor & Francis Publ. Available online: https://www.tandfonline. com/journals/icfs20 (accessed on 17 March 2023).
104. Fitzpatrick, T.B. Color Atlas and Synopsis of Clinical Dermatology: Common and Serious Diseases; McGraw-Hill: New York, NY, USA, 2001.
105. National Research Council, Committee on the Biological Effects of Ionizing Radiation. Health Effects of Exposure to Low Levels of Ionizing Radiation (BEIR V); National Academy Press: Washington, DC, USA, 1990.
106. Fink, C.A.; Bates, M.N. Melanoma and ionizing radiation: Is there a causal relationship? Radiat. Res. 2005, 164, 701–710. [CrossRef]
107. Telle-Lamberton, M.; Samson, E.; Caër, S.; Bergot, D.; Bard, D.; Bermann, F.; Gélas, J.M.; Giraud, J.M.; Hubert, P.; Metz-Flamant, C.; et al. External radiation exposure and mortality in a cohort of French nuclear workers. Occup. Environ. Med. 2007, 64, 694–700. [CrossRef]
108. Rajeevan, M.S.; Murray, J.; Oakley, L.; Lin, J.S.; Unger, E.R. Association of chronic fatigue syndrome with premature telomere attrition. J. Transl. Med. 2018, 16, 44. [CrossRef]
109. Rochette, P.J.; Brash, D.E. Human telomeres are hypersensitive to UV-induced DNA Damage and refractory to repair. PLoS Genet. 2010, 6, e1000926. [CrossRef] [PubMed]
110. Oikawa, S.; Tada-Oikawa, S.; Kawanishi, S. Site-specific DNA damage at the GGG sequence by UVA involves the acceleration of telomere shortening. Biochemistry 2001, 40, 4763–4768. [CrossRef] [PubMed]
111. Oikawa, S.; Kawanishi, S. Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett. 1999, 453, 365–368. [CrossRef] [PubMed]
112. Shim, G.; Ricoul, M.; Hempel, W.M.; Azzam, E.I.; Sabatier, L. Crosstalk between telomere maintenance and radiation effects: A key player in the process of radiation-induced carcinogenesis. Mutat. Res. Rev. Mutat. Res. 2014, 760, 1–17. [CrossRef] [PubMed]
113. Samuel, P.; Tsapekos, M.; de Pedro, N.; Liu, A.G.; Lippmeier, J.C.; Chen, S. Ergothioneine mitigates telomere shortening under oxidative stress conditions. J. Diet. Suppl. 2020, 19, 212–225. [CrossRef]
114. Marozik, P.; Mothersill, C.; Seymour, C.B.; Mosse, I.; Melnov, S. Bystander effects induced by serum from survivors of the Chornobyl accident. Exp. Hematol. 2007, 35, 55–63. [CrossRef]
115. Mosse, I.; Marozik, P.; Seymour, C.; Mothersill, C. The effect of melanin on the bystander effect in human keratinocytes. Mutat. Res. 2006, 597, 133–137. [CrossRef]
116. Lad, J.; Rusin, A.; Seymour, C.; Mothersill, C. An investigation into neutron-induced bystander effects: How low can you go? Environ. Res. 2019, 175, 84–99. [CrossRef]
117. Rusin, A.; Li, M.; Cocchetto, A.; Seymour, C.; Mothersill, C. Radiation exposure and mitochondrial insufficiency in chronic fatigue and immune dysfunction syndrome. Med. Hypotheses 2021, 154, 110647. [CrossRef]
118. Rusin, A.; Seymour, C.; Cocchetto, A.; Mothersill, C. Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability? Int. J. Mol. Sci. 2022, 23, 691. [CrossRef]
Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content.
【For more info:george.deng@wecistanche.com / WhatsApp:8613632399501】
