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Development studies based on Kampo theories for new treatment strategies and drug discoveries

趙 慶峰 富山大学

2021.09.30

概要

Traditional Chinese medicines (TCMs) are gaining more and more attention all over the world, due to their specific theory and long historical clinical practice. However, modern exploration of TCM derived functional compounds is significantly hindered by the inefficient elucidation of pharmacological functions over past decades, because conventional research methods are incapable of efficiently elucidating therapeutic potential of TCM conferred by multiple functional compounds.Based on traditional Chinese medicine theory and modern pharmacology research, this study summarized and explored the current common research ideas of Traditional Chinese Medicine.

Collectively, such critical review is expected to provide novel perspective-strategy that could significantly improve modern exploration and exploitation of TCM derived functional compounds that further promote new drug discovery and development against the complex diseases. In a few word, the analysis of TCMs are moving towards an integrative and comprehensive direction, in order to better address the inherent holistic nature of TCMs.

Chapter 1: Acquisition of basic data on 120 types of crude drugs used in Kampo medicine, the construction of a library to examine neuronal/glial cell function and expressed genes, and an investigation of changes in the expression of depression-related factors.

The component profiles of 120 types of crude drug extracts, which were supplied by the Institute of Natural Medicine, University of Toyama, were obtained by 3D-HPLC. The neuronal cell line N18TG2 and glial cell line C6Bu-1 were treated with two concentrations and 480 morphological photographs were obtained. RNA was also extracted from each treated cell and converted to cDNA to create a library. The expression levels of BNIP-3 mRNA, which we previously identified as an antidepressant-related factor, were investigated in the cDNA library using PCR. The results obtained revealed that BNIP-3 mRNA expression levels were increased by many of the herbal medicines in “Hochuekkito (補中益気湯:HET)”, but were decreased by the herbal medicines in “Sanou-shashin-to ( 三黄瀉心湯 :SST)” and “Orengedokuto (黄連解毒湯:OGT)”, which are used to treat anxiety.

Chapter 2: Reduced cytotoxicity of the combined extraction of Coptidis rhizoma and Rhei rhizoma: An example of the “herbal pair” theory.
Research on SST and OGT showed that both inhibited abnormal increases in Qi as described above, and Coptidis rhizoma (CR) and Rhei rhizoma (RR), which are included in OGT, suppressed the cytotoxicity of the other. Since the color of the solution when CR and RR were extracted together was lighter than when they were extracted individually, their components were analyzed by 3D-HPLC. The amount of CR-derived berberine was markedly lower in the co-extraction than in the CR alone extract. When the CR and CC extracts were combined in vitro, a new precipitate was formed. However, when cytotoxicity was assessed using the MTT assay, the inhibition of toxicity was only detected in the co-extraction, and not with in vitro mixing. The underlying mechanisms currently remain unclear; however, these results provide supportive evidence for the “herbal pair” theory in Chinese medicine.

Chapter 3: Stepwise detection of trace agonistic components in HET using electrophysiological techniques.
The majority of antidepressants are inhibitors of the serotonin 2C receptor (5-HT2CR), whereas HET has been identified as a stimulator. In this chapter, active compounds were analyzed using electrophysiological methods without omitting any of the intermediate steps of separation. The results obtained showed that a molecule with 283.14 exhibited high physiological activity; however, its structure was not elucidated because it may be an ultra-trace component. These results indicate that a trace amount of a component with high activity contributes to the effects of Chinese herbal medicine. Since this molecule was present at a trace amount, HET may have many agonistic components that have yet to be identified.

Chapter 4: Clarifying the pharmacological mechanisms of action of Shenfu Decoction on cardiovascular diseases using a network pharmacology approach.
New prescriptions may be developed based on the Kampo medicine theories. Numerous prescriptions have newly been developed and used in China to prevent the aggravation of COVID-19. Therefore, basic research was initiated with the aim of developing prescriptions to prevent heart failure caused by the side effects of anticancer drugs. In this chapter, experiments were performed on Shenfu Decoction (人参附子湯: SFD) and the genes contributing to its effects. The myoblast cell line H9C2, which differentiates to the cardiac type with a decrease in the percentage of serum in media and supplementation with retinoic acid, was treated with doxorubicin and SFD. A gene chip analysis followed by a network pharmacology and protein-protein network/module analysis were performed. The results obtained indicated that SFD significantly altered the expression of ubiquitination-related genes; therefore, it may play an important role in the treatment of heart failure. Information on hub genes will provide insights into the underlying molecular mechanisms and contribute to the development of effective novel Kampo prescriptions.

Collectively, the results of each chapter provide the following: 1) basic information on crude drugs in Chinese herbal medicine, 2) insights into the “herbal pair” theory, 3) a more detailed understanding of the effects of ultra-trace agonistic components that exert physiological effects, and 4) the outcomes of attempts to develop new Kampo prescriptions using novel combinations and their underlying molecular mechanisms of action. Although these results appear to be fragmented, research based on the basic concepts of classical Chinese medicine will contribute to the discovery of new theories and therapeutic drugs, and examples of this are described herein.

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参考文献

1. Tohda, M., Hayashi, H., Sukma, M. & Tanaka, K. BNIP-3: a novel candidate for an intrinsic depression-related factor found in NG108-15 cells treated with Hochu-ekki-to, a traditional oriental medicine, or typical antidepressants. Neurosci Res 62, 1–8 (2008).

2. Tohda, M., Mingmalairak, S., Murakami, Y. & Matsumoto, K. Enhanced expression of BCL2/adenovirus EIB 19-kDa-interacting protein 3 mRNA, a candidate for intrinsic depression-related factor, and effects of imipramine in the frontal cortex of stressed mice. Biol Pharm Bull 33, 53–57 (2010).

3. Tohda, M. MRI detection of the activated region in the rat brain by Hochuekki-to, a traditional oriental medicine, and the related expression of BNIP-3 mRNA, a candidate of depression-related factor. J Med Therap 2, (2018).

4. Tohda, M. & Mingmalairak, S. Evidence of Antidepressive Effects of a Wakan-yaku, Hochuekkito, in Depression Model Mice with Learned-Helplessness Behavior. Evid Based Complement Alternat Med 2013, 319073 (2013).

5. Tohda, M. Changes in the expression of BNIP-3 and other neuronal factors during the cultivation period of primary cultured rat cerebral cortical neurons and an assessment of each factor’s functions. Cell signalling and Trafficking 2, 1 (2014).

6. Dodson, M., Darley-Usmar, V. & Zhang, J. Cellular metabolic and autophagic pathways: traffic control by redox signaling. Free Radic Biol Med 63, 207–221 (2013).

7. Bellot, G. et al. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 29, 2570–2581 (2009).

8. Zhang, J. & Ney, P. A. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ 16, 939–946 (2009).

9. Jia, F., Mou, L. & Ge, H. Protective effects of ginsenoside Rb1 on H2O2-induced oxidative injury in human endothelial cell line (EA.hy926) via miR-210. Int J Immunopathol Pharmacol 33, 2058738419866021 (2019).

10. Tohda, M., Imaizumi, R., Sekiya, A., Itoh, N. & Nomura, Y. Studies on the activation mechanisms of guanylyl cyclase by serotonin, probably through a novel subtype of serotonin receptor (5-HTGC). Biol Pharm Bull 18, 1072–1075 (1995).

11. Yang, B., Qin, J., Nie, Y., Li, Y. & Chen, Q. Brain-derived neurotrophic factor propeptide inhibits proliferation and induces apoptosis in C6 glioma cells. Neuroreport 28, 726–730 (2017).

12. Chen, Y.-D. et al. Hyperthermia with different temperatures inhibits proliferation and promotes apoptosis through the EGFR/STAT3 pathway in C6 rat glioma cells. Mol Med Rep 16, 9401–9408 (2017).

13. Yin, B., Sheng, H., Lin, J., Zhou, H. & Zhang, N. The cell death of C6 astrocytoma cells induced by oridonin and its mechanism. Int J Clin Exp Pathol 5, 562–568 (2012).

14. Zhang, Z. et al. MicroRNA-124 inhibits the proliferation of C6 glioma cells by targeting Smad4. Int J Mol Med 40, 1226–1234 (2017).

15. Bawari, S. et al. Targeting BDNF signaling by natural products: Novel synaptic repair therapeutics for neurodegeneration and behavior disorders. Pharmacological Research 148, 104458 (2019).

16. Sakai, H. et al. Plag1 regulates neuronal gene expression and neuronal differentiation of neocortical neural progenitor cells. Genes Cells 24, 650–666 (2019).

17. Pandey, A. et al. Critical role of the miR-200 family in regulating differentiation and proliferation of neurons. Journal of Neurochemistry 133, 640–652 (2015).

18. Tohda, M. & Watanabe, H. The Wakan-yaku Universe: A Useful Authorized Traditional Concept for Developing Novel Therapeutic Categories and Medicinal Drugs. Biological and Pharmaceutical Bulletin 41, 1627–1631 (2018).

19. Srivastava, A. et al. Secretome of Differentiated PC12 Cells Enhances Neuronal Differentiation in Human Mesenchymal Stem Cells Via NGF-Like Mechanism. Mol Neurobiol 55, 8293–8305 (2018).

20. Protective effects of ginsenoside Rb1 on H2O2-induced oxidative injury in human endothelial cell line (EA.hy926) via miR-210 - Fubao Jia, Lei Mou, Hanming Ge, 2019. https://journals.sagepub.com/doi/10.1177/2058738419866021.

21. Kubli, D. A., Quinsay, M. N., Huang, C., Lee, Y. & Gustafsson, A. B. Bnip3 functions as a mitochondrial sensor of oxidative stress during myocardial ischemia and reperfusion. Am J Physiol Heart Circ Physiol 295, H2025-2031 (2008).

22. Dhingra, R. et al. Bidirectional regulation of nuclear factor-κB and mammalian target of rapamycin signaling functionally links Bnip3 gene repression and cell survival of ventricular myocytes. Circ Heart Fail 6, 335–343 (2013).

23. Tohda, M. & Watanabe, H. The Wakan-yaku Universe: A Useful Authorized Traditional Concept for Developing Novel Therapeutic Categories and Medicinal Drugs. Biological and Pharmaceutical Bulletin 41, 1627–1631 (2018).

24. Profiling of 120 types of herbal extracts and their effects on morphology in cultured neuronal or glial cell lines, followed by RNA extraction for a cDNA library: Consideration for use in studies based on Kampo theories - Tohda - 2021 - Traditional & Kampo Medicine - Wiley Online Library. https://onlinelibrary.wiley.com/doi/full/10.1002/tkm2.1274.

25. Tohda, M., Imaizumi, R., Sekiya, A., Itoh, N. & Nomura, Y. Studies on the activation mechanisms of guanylyl cyclase by serotonin, probably through a novel subtype of serotonin receptor (5-HTGC). Biol Pharm Bull 18, 1072–1075 (1995).

26. Kobashi, K., Nishimura, T., Kusaka, M., Hattori, M. & Namba, T. Metabolism of sennosides by human intestinal bacteria. Planta Med 40, 225–236 (1980).

27. Fukuchi, M. et al. Screening inducers of neuronal BDNF gene transcription using primary cortical cell cultures from BDNF-luciferase transgenic mice. Sci Rep 9, 11833 (2019).

28. Tohda, M. & Watanabe, H. The Wakan-yaku Universe: A Useful Authorized Traditional Concept for Developing Novel Therapeutic Categories and Medicinal Drugs. Biological and Pharmaceutical Bulletin 41, 1627–1631 (2018).

29. Tohda, M. & Mingmalairak, S. Evidence of Antidepressive Effects of a Wakan-yaku, Hochuekkito, in Depression Model Mice with Learned-Helplessness Behavior. Evid Based Complement Alternat Med 2013, 319073 (2013).

30. Watari, H., Shimada, Y., Matsui, M. & Tohda, C. Kihito, a Traditional Japanese Kampo Medicine, Improves Cognitive Function in Alzheimer’s Disease Patients. Evid Based Complement Alternat Med 2019, 4086749 (2019).

31. M, T., M, A.-F. a.-F., S, N. & H, W. Effects of Hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang), a Kampo medicine, on serotonin 2C subtype receptor-evoked current response and the receptor mRNA expression. Journal of Traditional Medicines 17, 34–40 (2000).

32. Tohda, M., Takasu, T. & Nomura, Y. Effects of antidepressants on serotonin-evoked current in Xenopus oocytes injected with rat brain mRNA. Eur J Pharmacol 166, 57–63 (1989).

33. Tohda, M. & Watanabe, H. Imipramine-induced increase in 5-HT2C receptor mRNA level in the rat brain. Neurosci Res 24, 189–193 (1996).

34. Nomura, Y., Kaneko, S., Kato, K., Yamagishi, S. & Sugiyama, H. Inositol phosphate formation and chloride current responses induced by acetylcholine and serotonin through GTP-binding proteins in Xenopus oocyte after injection of rat brain messenger RNA. Brain Res 388, 113–123 (1987).

35. Arellano, R. O., Garay, E. & Miledi, R. Muscarinic receptor heterogeneity in follicle-enclosed Xenopus oocytes. J Physiol 521 Pt 2, 409–419 (1999).

36. Lübbert, H. et al. cDNA cloning of a serotonin 5-HT1C receptor by electrophysiological assays of mRNA-injected Xenopus oocytes. Proc Natl Acad Sci U S A 84, 4332–4336 (1987).

37. Tohda, M., Hayashi, H., Sukma, M. & Tanaka, K. BNIP-3: a novel candidate for an intrinsic depression-related factor found in NG108-15 cells treated with Hochu-ekki-to, a traditional oriental medicine, or typical antidepressants. Neurosci Res 62, 1–8 (2008).

38. Tohda, M., Mingmalairak, S., Murakami, Y. & Matsumoto, K. Enhanced expression of BCL2/adenovirus EIB 19-kDa-interacting protein 3 mRNA, a candidate for intrinsic depression-related factor, and effects of imipramine in the frontal cortex of stressed mice. Biol Pharm Bull 33, 53–57 (2010).

39. Tohda, M. Changes in the expression of BNIP-3 and other neuronal factors during the cultivation period of primary cultured rat cerebral cortical neurons and an assessment of each factor’s functions. Cell signalling and Trafficking 2, 1 (2014).

40. Tohda, M. MRI detection of the activated region in the rat brain by Hochuekki-to, a traditional oriental medicine, and the related expression of BNIP-3 mRNA, a candidate of depression-related factor. J Med Therap 2, (2018).

41. Yoshiya, T. et al. Prospective, randomized, cross-over pilot study of the effects of Rikkunshito, a Japanese traditional herbal medicine, on anorexia and plasma-acylated ghrelin levels in lung cancer patients undergoing cisplatin-based chemotherapy. Invest New Drugs 38, 485–492 (2020).

42. Matsumoto, C. et al. Psychological stress in aged female mice causes acute hypophagia independent of central serotonin 2C receptor activation. PLoS One 12, e0187937 (2017).

43. Schellekens, H. et al. Ghrelin’s Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction. ACS Chem Neurosci 6, 1186–1197 (2015).

44. Howell, E. et al. Glucagon-Like Peptide-1 (GLP-1) and 5-Hydroxytryptamine 2c (5-HT2c) Receptor Agonists in the Ventral Tegmental Area (VTA) Inhibit Ghrelin-Stimulated Appetitive Reward. Int J Mol Sci 20, E889 (2019).

45. Wang, S. et al. Compatibility art of traditional Chinese medicine: from the perspective of herb pairs. J Ethnopharmacol 143, 412–423 (2012).

46. Lloyd-Jones DM, Leip EP, Larson MG, d’Agostino RB, Beiser A, Wilson PW, Wolf PA, Levy D. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006; 113:791-798.

47. Wang J, Qi F. Traditional Chinese medicine to treat COVID-19: the importance of evidence-based research. Drug Discov Ther. 2020; 14:149-150.

48. Kitazawa T, Park CH, Hiratani K, Choi JS, Yokozawa T. Efficacy of Chinese prescription Kangen-karyu for patient with metabolic syndrome. Drug Discov Ther. 2020; 14:54-57.

49. Gu P, Chen H. Modern bioinformatics meets traditional Chinese medicine. Brief Bioinform. 2014; 15:984-1003.

50. Zhao J, Yang J, Tian S, Zhang W. A survey of web resources and tools for the study of TCM network pharmacology. Quantitative Biology. 2019; 7:17-29.

51. Fang J, Wang L, Wu T, Yang C, Gao L, Cai H, Liu J, Fang S, Chen Y, Tan W, Wang Q. Network pharmacology-based study on the mechanism of action for herbal medicines in Alzheimer treatment. J Ethnopharmacol. 2017; 196:281-292.

52. Zhao J, Jiang P, Zhang W. Molecular networks for the study of TCM pharmacology. Brief Bioinform. 2010; 11:417-430.

53. Li B, Xu X, Wang X, Yu H, Li X, Tao W, Wang Y, Yang L. A systems biology approach to understanding the mechanisms of action of chinese herbs for treatment of cardiovascular disease. Int J Mol Sci. 2012; 13:13501-13520.

54. Yan X, Wu H, Ren J, Liu Y, Wang S, Yang J, Qin S, Wu D. Shenfu Formula reduces cardiomyocyte apoptosis in heart failure rats by regulating microRNAs. J Ethnopharmacol. 2018; 227:105-112.

55. Zheng SY, Sun J, Zhao X, Xu JG. Protective effect of shen-fu on myocardial ischemia-reperfusion injury in rats. Am J Chin Med. 2004; 32:209-220.

56. Yang D, Wang X, Wu Y, Lu B, Yuan A, Leon C, Guo N. Urinary Metabolomic Profiling Reveals the Effect of Shenfu Decoction on Chronic Heart Failure in Rats. Molecules. 2015; 20:11915-11929.

57. Chen Y, Yu R, Jiang L, Zhang Q, Li B, Liu H, Xu G. A Comprehensive and Rapid Quality Evaluation Method of Traditional Chinese Medicine Decoction by Integrating UPLC-QTOF-MS and UFLC-QQQ-MS and its Application. Molecules. 2019; 24.

58. He JL, Zhao JW, Ma ZC, Wang YG, Liang QD, Tan HL, Xiao CR, Tang XL, Gao Y. Serum Pharmacochemistry Analysis Using UPLC-Q-TOF/MS after Oral Administration to Rats of Shenfu Decoction. Evid Based Complement Alternat

59. Berger SI, Iyengar R. Network analyses in systems pharmacology. Bioinformatics. 2009; 25:2466-2472.

60. Zhou F, Hao G, Zhang J, Zheng Y, Wu X, Hao K, Niu F, Luo D, Sun Y, Wu L, Ye W, Wang G. Protective effect of 23-hydroxybetulinic acid on doxorubicin-induced cardiotoxicity: a correlation with the inhibition of carbonyl reductase-mediated metabolism. Br J Pharmacol. 2015; 172:5690-5703.

61. Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, Jensen LJ, von Mering C. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017; 45:D362-D368.

62. Bader GD, Hogue CW. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics. 2003; 4:2.

63. Liao Y, Wang J, Jaehnig EJ, Shi Z, Zhang B. WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 2019; 47:W199-W205.

64. The Gene Ontology C. Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Res. 2017; 45:D331-D338.

65. Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017; 45:D353-D361.

66. Warde-Farley D, Donaldson SL, Comes O, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010; 38:W214-220.

67. Li S, Zhang B, Jiang D, Wei Y, Zhang N. Herb network construction and co-module analysis for uncovering the combination rule of traditional Chinese herbal formulae. BMC Bioinformatics. 2010; 11 Suppl 11:S6.

68. Ding F, Zhang Q, Ung CO, Wang Y, Han Y, Hu Y, Qi J. An analysis of chemical ingredients network of Chinese herbal formulae for the treatment of coronary heart disease. PLoS One. 2015; 10:e0116441.

69. Guimera R, Nunes Amaral LA. Functional cartography of complex metabolic networks. Nature. 2005; 433:895-900.

70. Wang X, Robbins J. Proteasomal and lysosomal protein degradation and heart disease. J Mol Cell Cardiol. 2014; 71:16-24.

71. Powell SR, Herrmann J, Lerman A, Patterson C, Wang X. The ubiquitin-proteasome system and cardiovascular disease. Prog Mol Biol Transl Sci. 2012; 109:295-346.

72. Li YF, Wang X. The role of the proteasome in heart disease. Biochim Biophys Acta. 2011; 1809:141-149.

73. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004; 56:185-229.

74. Ranek MJ, Wang X. Activation of the ubiquitin-proteasome system in doxorubicin cardiomyopathy. Curr Hypertens Rep. 2009; 11:389-395.

75. Sishi BJ, Loos B, van Rooyen J, Engelbrecht AM. Doxorubicin induces protein ubiquitination and inhibits proteasome activity during cardiotoxicity. Toxicology. 2013; 309:23-29.

76. Bulteau AL, Lundberg KC, Humphries KM, Sadek HA, Szweda PA, Friguet B, Szweda LI. Oxidative modification and inactivation of the proteasome during coronary occlusion/reperfusion. J Biol Chem. 2001; 276:30057-30063.

77. Yu M, Ye L, Bian J, Ma L, Zheng C, Guo H. Effect of Jiawei Shenfu decoction on tumor necrosis factor-alpha and nuclear factor-kappa B in patients who have chronic heart failure with syndromes of deficiency of heart Yang. J Tradit Chin Med. 2019; 39:418-424.

78. Chen RJ, Rui QL, Wang Q, Tian F, Wu J, Kong XQ. Shenfu injection attenuates lipopolysaccharide-induced myocardial inflammation and apoptosis in rats. Chin J Nat Med. 2020; 18:226-233.

79. Zhu J, Song W, Xu S, Ma Y, Wei B, Wang H, Hua S. Shenfu Injection Promotes Vasodilation by Enhancing eNOS Activity Through the PI3K/Akt Signaling Pathway In Vitro. Front Pharmacol. 2020; 11:121.

80. Ni J, Shi Y, Li L, Chen J, Li L, Li M, Zhu J, Zhu Y, Fan G. Cardioprotection against Heart Failure by Shenfu Injection via TGF-beta/Smads Signaling Pathway. Evid Based Complement Alternat Med. 2017; 2017:7083016.

81. Wang YY, Li YY, Li L, Yang DL, Zhou K, Li YH. Protective Effects of Shenfu Injection against Myocardial Ischemia-Reperfusion Injury via Activation of eNOS in Rats. Biol Pharm Bull. 2018; 41:1406-1413.

82. Willis MS, Townley-Tilson WH, Kang EY, Homeister JW, Patterson C. Sent to destroy: the ubiquitin proteasome system regulates cell signaling and protein quality control in cardiovascular development and disease. Circ Res. 2010; 106:463-478.

83. Zou J, Ma W, Li J, Littlejohn R, Zhou H, Kim IM, Fulton DJR, Chen W, Weintraub NL, Zhou J, Su H. Neddylation mediates ventricular chamber maturation through repression of Hippo signaling. Proc Natl Acad Sci U S A. 2018; 115:E4101-E4110.

84. Yaguchi-Saito A, Yamamoto K, Sengoku T, Suka M, Sato T, Hinata M, Nakamura T, Nakayama T, Yamamoto M. Evaluation of rapid drug safety communication materials for patients in Japan. Drug Discov Ther. 2021; 15:101-107.

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