یکشنبه 7 دی 1404
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دوره 23، شماره 10 - ( 7-1404 )
جلد 23 شماره 10 صفحات 786-775 |
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Alaei A, Azizi M M, Homayoun M. Diabetes and male infertility: A review of sperm chromatin damage and epigenetic effects. IJRM 2025; 23 (10) :775-786
URL: http://ijrm.ir/article-1-3596-fa.html
URL: http://ijrm.ir/article-1-3596-fa.html
دیابت و ناباروری مردان: مروری بر آسیب ساختاری کروماتین اسپرم و اثرات اپی ژنتیک. International Journal of Reproductive BioMedicine. 1404; 23 (10) :775-786
چکیده: (325 مشاهده)
دیابت شیرین (DM) به عنوان یک معضل جهانی سلامت، باروری مردان را عمدتاً از طریق تأثیرات منفی بر یکپارچگی ساختار کروماتین و DNA اسپرم تحت تأثیر قرار میدهد. این مقاله مروری به بررسی چگونگی اختلال DM در فرآیند اسپرماتوژنز میپردازد که عمدتاً از طریق القای استرس اکسیداتیو رخ میدهد و میتواند منجر به قطعه قطعه شدن قابل توجه DNA و مختل شدن یکپارچگی کروماتین در اسپرماتوزوئیدها شود. شواهد نشان میدهند که حتی در مردان دیابتی با پارامترهای ظاهرا طبیعی آزمایش اسپرم، ممکن است آسیب پنهان DNA اسپرم وجود داشته باشد. مطالعات به طور مستمر شاخص¬های قطعه-قطعه شدن DNA اسپرم و حساسیت بیشتر آن به تغییر ساختار را در مردان دیابتی گزارش میکنند. علاوه بر این، امکان تأثیر دیابت پدری بر سلامت فرزندان از طریق تغییرات اپیژنتیکی در DNA اسپرم، از جمله الگوهای متیلاسیون DNA و محتوای microRNA، مورد بحث قرار گرفته است که میتواند مکانیسمی برای انتقال صفات متابولیک به نسل بعد باشد. در پایان، مزایای درمان دیابت در بهبود کیفیت اسپرم و سلامت کروماتین مورد بررسی قرار گرفته است. شواهد بالینی نشان میدهند که مداخلات درمانی، به ویژه کنترل شدید قند خون، میتواند منجر به بهبود قابل اندازهگیری در یکپارچگی DNA اسپرم شود. برای تهیه این مقاله، جستجوی جامعی در پایگاههای اطلاعاتی علمی معتبر از جمله PubMed، Scopus و Web of Science با استفاده از کلیدواژههایی مانند "دیابت ملیتوس"، "ناباروری مردان"، "ساختار کروماتین اسپرم"، "قطعه قطعه شدن DNA" و "اپیژنتیک" انجام شد. این مرور به تحلیل مکانیسمهای احتمالی تأثیرات دیابت بر باروری مردان با تغییر ساختار کروماتین اسپرم و یکپارچگی DNA و تأثیر درمان دیابت بر کیفیت اسپرم میپردازد. همچنین مفهوم نوظهور تأثیرات اپیژنتیکی و نقش آن در این زمینه مورد بحث قرار گرفته است.
نوع مطالعه: Review article |
فهرست منابع
1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes Res Clin Pract 2019; 157: 107843. [DOI:10.1016/j.diabres.2019.107843] [PMID]
2. Talebi AR, Mangoli E, Nahangi H, Anvari M, Pourentezari M, Halvaei I. Vitamin C attenuates detrimental effects of diabetes mellitus on sperm parameters, chromatin quality and rate of apoptosis in mice. Eur J Obstet Gynecol Reprod Biol 2014; 181: 32-36. [DOI:10.1016/j.ejogrb.2014.07.007] [PMID]
3. Alam S, Hasan MK, Neaz S, Hussain N, Hossain MF, Rahman T. diabetes mellitus: insights from epidemiology, biochemistry, risk factors, diagnosis, complications and comprehensive management. Diabetology 2021; 2: 36-50. [DOI:10.3390/diabetology2020004]
4. Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nat Rev Endocrinol 2009; 5: 219-226. [DOI:10.1038/nrendo.2009.21] [PMID]
5. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 2003; 52: 102-110.
https://doi.org/10.2337/diabetes.52.9.2304 [DOI:10.2337/diabetes.52.1.102]
6. Al-Salihi AA, Ismael KI, AL-Saadi RR, Saeed BT. the role of genetic and environmental factors in the etiology of type 2 diabetes. Ann Roman Soc Cell Biol 2021; 25: 11344-11355.
7. Kaul K, Tarr JM, Ahmad SI, Kohner EM, Chibber R. Introduction to diabetes mellitus. Adv Exp Med Biol 2012; 771: 1-11. [DOI:10.1007/978-1-4614-5441-0_1] [PMID]
8. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37 (Suppl.): S81-S90. [DOI:10.2337/dc14-S081] [PMID]
9. Mouri M, Badireddy M. Hyperglycemia. StatPearls [Internet]. 2020.
10. Keating ST, Plutzky J, El-Osta A. Epigenetic changes in diabetes and cardiovascular risk. Circ Res 2016; 118: 1706-1722. [DOI:10.1161/CIRCRESAHA.116.306819] [PMID] [PMCID]
11. Zhang P, Li T, Wu X, Nice EC, Huang C, Zhang Y. Oxidative stress and diabetes: Antioxidative strategies. Front Med 2020; 14: 583-600. [DOI:10.1007/s11684-019-0729-1] [PMID]
12. Ritchie C, Ko EY. Oxidative stress in the pathophysiology of male infertility. Andrologia 2021; 53: e13581. [DOI:10.1111/and.13581] [PMID]
13. Mohammad MHS, Ameen EM. Impact of diabetes and obesity on human fertility and semen quality. Zanco J Pure Appl Sci 2021; 33: 42-54. [DOI:10.21271/ZJPAS.33.1.6]
14. Mostafa T, Abdel-Hamid IA. Ejaculatory dysfunction in men with diabetes mellitus. World J Diabetes 2021; 12: 954-974. [DOI:10.4239/wjd.v12.i7.954] [PMID] [PMCID]
15. Aly HAA. Mitochondria-mediated apoptosis induced testicular dysfunction in diabetic rats: Ameliorative effect of resveratrol. Endocrinology 2021; 162: bqab018. [DOI:10.1210/endocr/bqab018] [PMID]
16. Roessner C, Paasch U, Kratzsch J, Glander H-J, Grunewald S. Sperm apoptosis signalling in diabetic men. Reprod Biomedi Online 2012; 25: 292-299. [DOI:10.1016/j.rbmo.2012.06.004] [PMID]
17. Mangoli E, Talebi AR, Anvari M, Pourentezari M. Effects of experimentally-induced diabetes on sperm parameters and chromatin quality in mice. Iran J Reprod Med 2013; 11: 53-60.
18. Zhu X-B, Niu Z-H, Fan W-M, Sheng C-S, Chen Q. Type 2 diabetes mellitus and the risk of male infertility: A Mendelian randomization study. Front Endocrinol (Lausanne) 2023; 14: 1279058. [DOI:10.3389/fendo.2023.1279058] [PMID] [PMCID]
19. Agbaje IM, Rogers DA, McVicar CM, McClure N, Atkinson AB, Mallidis C, et al. Insulin dependant diabetes mellitus: Implications for male reproductive function. Hum Reprod 2007; 22: 1871-1877. [DOI:10.1093/humrep/dem077] [PMID]
20. Lotti F, Maggi M. Effects of diabetes mellitus on sperm quality and fertility outcomes: Clinical evidence. Andrology 2023; 11: 399-416. [DOI:10.1111/andr.13342] [PMID]
21. Homayoun M, Sajedi N, Soleimani M. In vitro evaluation of the pogostone effects on the expression of PTEN and DACT1 tumor suppressor genes, cell cycle, and apoptosis in ovarian cancer cell line. Res Pharm Sci 2022; 17: 164-175. [DOI:10.4103/1735-5362.335175] [PMID] [PMCID]
22. Akhatova A, Jones C, Coward K, Yeste M. How do lifestyle and environmental factors influence the sperm epigenome? Effects on sperm fertilising ability, embryo development, and offspring health. Clin Epigenetics 2025; 17: 7. [DOI:10.1186/s13148-025-01815-1] [PMID] [PMCID]
23. Thorson JLM, Maamar MB, Skinner MK. Epigenetics in sperm, epigenetic diagnostics, and transgenerational inheritance. In: Simon C, Rubio C. Handbook of genetic diagnostic technologies in reproductive medicine. 2nd Ed. USA: CRC Press; 2022. [DOI:10.1201/9781003024941-7]
24. Sadler-Riggleman I, Skinner MK. Environment and the epigenetic transgenerational inheritance of disease. UK: Caister Academic Press; 2015. [DOI:10.21775/9781910190074.15]
25. Hanson MA, Skinner MK. Developmental origins of epigenetic transgenerational inheritance. Environ Epigenet 2016; 2: dvw002. [DOI:10.1093/eep/dvw002] [PMID] [PMCID]
26. Balder P, Jones C, Coward K, Yeste M. Sperm chromatin: Evaluation, epigenetic signatures and relevance for embryo development and assisted reproductive technology outcomes. Eur J Cell Biol 2024; 103: 151429. [DOI:10.1016/j.ejcb.2024.151429] [PMID]
27. Chen H, Alves MBR, Belleannée C. Contribution of epididymal epithelial cell functions to sperm epigenetic changes and the health of progeny. Hum Reprod Update 2021; 28: 51-66. [DOI:10.1093/humupd/dmab029] [PMID]
28. Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature 2009; 460: 473-478. [DOI:10.1038/nature08162] [PMID] [PMCID]
29. Meistrich ML. Histone and basic nuclear protein transitions in mammalian spermatogenesis. In: Stein GS, Stein GL. Histones and other basic nuclear proteins. 1st Ed. United States: CRC Press; 2024. 165-182. [DOI:10.1201/9781003574552-5]
30. Cheng J, Gu Y, Wang Y, Xu J, Wang G, Wang Y, et al. Fam170a deficiency causes male infertility by impairing histone-to-protamine exchange during mouse spermiogenesis. Nucleic Acids Res 2025; 53: gkaf023. [DOI:10.1093/nar/gkaf023] [PMID] [PMCID]
31. Drevet JR, Hallak J, Nasr-Esfahani M-H, Aitken RJ. Reactive oxygen species and their consequences on the structure and function of mammalian spermatozoa. Antioxid Redox Signal 2022; 37: 481-500. [DOI:10.1089/ars.2021.0235] [PMID]
32. Dutta S, Henkel R, Agarwal A. Comparative analysis of tests used to assess sperm chromatin integrity and DNA fragmentation. Andrologia 2021; 53: e13718. [DOI:10.1111/and.13718] [PMCID]
33. Kaltsas A, Moustakli E, Zikopoulos A, Georgiou I, Dimitriadis F, Symeonidis EN, et al. Impact of advanced paternal age on fertility and risks of genetic disorders in offspring. Genes (Basel) 2023; 14: 486. [DOI:10.3390/genes14020486] [PMID] [PMCID]
34. Evenson DP, Larson KL, Jost LK. Sperm chromatin structure assay: Its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. J Androl 2002; 23: 25-43. [DOI:10.1002/j.1939-4640.2002.tb02599.x] [PMID]
35. Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, et al. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature 2017; 549: 519-522. [DOI:10.1038/nature24018] [PMID]
36. Simon L, Emery BR, Carrell DT. Diagnosis and impact of sperm DNA alterations in assisted reproduction. Best Pract Res Clin Obstet Gynaecol 2017; 44: 38-56. [DOI:10.1016/j.bpobgyn.2017.07.003] [PMID]
37. de la Iglesia A, Jodar M, Oliva R, Castillo J. Insights into the sperm chromatin and implications for male infertility from a protein perspective. WIREs Mech Dis 2023; 15: e1588. [DOI:10.1002/wsbm.1588] [PMID]
38. Ghasemnezhad Targhi R, Homayoun M, Mansouri S, Soukhtanloo M, Soleymanifard Sh, Seghatoleslam M. Radio protective effect of black mulberry extract on radiation-induced damage in bone marrow cells and liver in the rat. Radiation Physics and Chemistry 2017; 130: 297-302. [DOI:10.1016/j.radphyschem.2016.08.030]
39. Punjabi U, Peeters K, De Neubourg D. Sperm nuclear maturity and chromatin stability in subfertile patients: Density gradient centrifugation is fair but non-discriminative in selecting the right population. Reprod Biol 2019; 19: 316-321. [DOI:10.1016/j.repbio.2019.11.003] [PMID]
40. Björndahl L, Kvist U. Structure of chromatin in spermatozoa. Adv Exp Med Biol 2014; 79: 1-11.
2 [DOI:10.1007/978-1-4614-7783-9_1]
41. Panner Selvam MK, Ambar RF, Agarwal A, Henkel R. Etiologies of sperm DNA damage and its impact on male infertility. Andrologia 2021; 53: e13706. [DOI:10.1111/and.13706] [PMCID]
42. O'Flaherty C, Matsushita-Fournier D. Reactive oxygen species and protein modifications in spermatozoa. Biol Reprod 2017; 97: 577-585. [DOI:10.1093/biolre/iox104] [PMID]
43. Erenpreiss J, Spano M, Erenpreisa J, Bungum M, Giwercman A. Sperm chromatin structure and male fertility: Biological and clinical aspects. Asian J Androl 2006; 8: 11-29. [DOI:10.1111/j.1745-7262.2006.00112.x] [PMID]
44. Cho C-L, Agarwal A. Role of sperm DNA fragmentation in male factor infertility: A systematic review. Arab J Urol 2017; 16: 21-34. [DOI:10.1016/j.aju.2017.11.002] [PMID] [PMCID]
45. Akbarian F, Rahmani M, Tavalaee M, Abedpoor N, Taki M, Ghaedi K, et al. Effect of different high-fat and advanced Glycation end-products diets in obesity and diabetes-prone C57BL/6 Mice on sperm function. Int J Fertil Steril 2021; 15: 226-233.
46. Mallidis C, Agbaje IM, Rogers DA, Glenn JV, Pringle R, Atkinson AB, et al. Advanced glycation end products accumulate in the reproductive tract of men with diabetes. Int J Androl 2009; 32: 295-305. [DOI:10.1111/j.1365-2605.2007.00849.x] [PMID]
47. Kangralkar V, Patil SD, Bandivadekar R. Oxidative stress and diabetes: A review. Int J Pharm Appl 2010; 1: 38-45.
48. Ayepola OR, Brooks NL, Oguntibeju OO. Oxidative stress and diabetic complications: The role of antioxidant vitamins and flavonoids. In: Oguntibeju OO. Antioxidant-antidiabetic agents and human health. UK: Utechopen; 2014: 923-931.
49. Muratori M, Tamburrino L, Marchiani S, Cambi M, Olivito B, Azzari C, et al. Investigation on the origin of sperm DNA fragmentation: Role of apoptosis, immaturity and oxidative stress. Mol Med 2015; 21: 109-122. [DOI:10.2119/molmed.2014.00158] [PMID] [PMCID]
50. Imani M, Talebi AR, Fesahat F, Rahiminia T, Seifati SM, Dehghanpour F. Sperm parameters, DNA integrity, and protamine expression in patients with type II diabetes mellitus. J Obstet Gynaecol 2021; 41: 439-446. [DOI:10.1080/01443615.2020.1744114] [PMID]
51. Kimmins S, Sassone-Corsi P. Chromatin remodelling and epigenetic features of germ cells. Nature 2005; 434: 583-589. [DOI:10.1038/nature03368] [PMID]
52. Turek-Plewa J, Jagodzinski PP. The role of mammalian DNA methyltransferases in the regulation of gene expression. Cell Mol Biol Lett 2005; 10: 631-647.
53. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429: 457-463. [DOI:10.1038/nature02625] [PMID]
54. Homayoun M, Ghasemnezhad Targhi R, Soleimani M. Anti-proliferative and anti-apoptotic effects of grape seed extract on chemo-resistant OVCAR-3 ovarian cancer cells. Res Pharm Sci 2020; 15: 390-400. [DOI:10.4103/1735-5362.293517] [PMID] [PMCID]
55. Bartke T, Vermeulen M, Xhemalce B, Robson SC, Mann M, Kouzarides T. Nucleosome-interacting proteins regulated by DNA and histone methylation. Cell 2010; 143: 470-484. [DOI:10.1016/j.cell.2010.10.012] [PMID] [PMCID]
56. Guibert S, Weber M. Functions of DNA methylation and hydroxymethylation in mammalian development. Curr Top Dev Biol 2013; 104: 47-83. [DOI:10.1016/B978-0-12-416027-9.00002-4] [PMID]
57. Kaneshiro KR, Rechtsteiner A, Strome S. Sperm-inherited H3K27me3 impacts offspring transcription and development in C. elegans. Nat Commun 2019; 10: 1271. [DOI:10.1038/s41467-019-09141-w] [PMID] [PMCID]
58. Braun K, Champagne FA. Paternal influences on offspring development: Behavioural and epigenetic pathways. J Neuroendocrinol 2014; 26: 697-706. [DOI:10.1111/jne.12174] [PMID]
59. Volkmar M, Dedeurwaerder S, Cunha DA, Ndlovu MN, Defrance M, Deplus R, et al. DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J 2012; 31: 1405-1426. [DOI:10.1038/emboj.2011.503] [PMID] [PMCID]
60. Wei Y, Yang C-R, Wei Y-P, Zhao Z-A, Hou Y, Schatten H, et al. Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Nati Acad Sci USA 2014; 111: 1873-1878. [DOI:10.1073/pnas.1321195111] [PMID] [PMCID]
61. Bosman E, Esterhuizen AD, Rodrigues FA. Influence of male hyperinsulinemia on IVF outcome. Andrologia 2015; 47: 91-96. [DOI:10.1111/and.12227] [PMID]
62. Bosman E, Esterhuizen AD, Rodrigues FA, Becker PJ, Hoffmann WA. Prevalence of hyperinsulinaemia among normozoospermic donors at M edfem C linic, S outh A frica. Andrologia 2013; 45: 18-25. [DOI:10.1111/j.1439-0272.2012.01303.x] [PMID]
63. Pourentezari M, Talebi AR, Mangoli E, Anvari M, Rahimipour M. Additional deleterious effects of alcohol consumption on sperm parameters and DNA integrity in diabetic mice. Andrologia 2016; 48: 564-569. [DOI:10.1111/and.12481] [PMID]
64. Singh S, Malini T, Rengarajan S, Balasubramanian K. Impact of experimental diabetes and insulin replacement on epididymal secretory products and sperm maturation in albino rats. J Cell Biochem 2009; 108: 1094-1101. [DOI:10.1002/jcb.22337] [PMID]
65. Bosman E, Esterhuizen AD, Rodrigues FA, Becker PJ, Hoffmann WA. Effect of metformin therapy and dietary supplements on semen parameters in hyperinsulinaemic males. Andrologia 2015; 47: 974-979. [DOI:10.1111/and.12366] [PMID]
66. Alves MG, Martins AD, Vaz CV, Correia S, Moreira PI, Oliveira PF, et al. Metformin and male reproduction: Effects on S ertoli cell metabolism. Br J Pharmacol 2014; 171: 1033-1042. [DOI:10.1111/bph.12522] [PMID] [PMCID]
67. Mahdi K, AL-Hady FA. Effect of repaglinide and Metformin as anti-diabetic drugs on epidydimal sperm parameters. Anne Roman Soc Cell Biol 2021; 25: 11864-11887.
68. Öztaş E, Yılmaz TE, Güzel E, Sezer Z, Okyar A, Özhan G. Gliclazide alone or in combination with atorvastatin ameliorated reproductive damage in streptozotocin-induced type 2 diabetic male rats. Saudi Pharm J 2019; 27: 422-431. [DOI:10.1016/j.jsps.2019.01.003] [PMID] [PMCID]
69. Babaei M, Alizadeh-Fanalou Sh, Nourian A, Yarahmadi S, Farahmandian N, Nabi-Afjadi M, et al. Evaluation of testicular glycogen storage, FGF21 and LDH expression and physiological parameters of sperm in hyperglycemic rats treated with hydroalcoholic extract of Securigera Securidaca seeds, and Glibenclamide. Reprod Biol Endocrinol 2021; 19: 104. [DOI:10.1186/s12958-021-00794-1] [PMID] [PMCID]
70. Malekifard F, Dalirezh N, Soleimanzadeh A. Modulatory effect of pioglitazone on sperm parameters and oxidative stress, apoptotic and inflammatory biomarkers in testes of streptozotocin-induced diabetic rats. Int J Med Lab 2018; 5: 19-34.
71. Tsampoukas G, Tharakan T, Narayan Y, Khan F, Cayetano A, Papatsoris A, et al. Investigating the therapeutic options for diabetes‐associated male infertility as illustrated in animal experimental models. Andrologia 2022; 54: e14521. [DOI:10.1111/and.14521] [PMID]
72. Mallidis C, Agbaje I, McClure N, Kliesch S. The influence of diabetes mellitus on male reproductive function: A poorly investigated aspect of male infertility. Urologe A 2011; 50: 33-37. [DOI:10.1007/s00120-010-2440-3] [PMID]
73. Ding G-L, Liu Y, Liu M-E, Pan J-X, Guo M-X, Sheng J-Z, et al. The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis. Asian J Androl 2015; 17: 948-953. [DOI:10.4103/1008-682X.150844] [PMID] [PMCID]
74. Minas A, Camargo M, Alves MG, Bertolla RP. Effects of diabetes-induced hyperglycemia on epigenetic modifications and DNA packaging and methylation during spermatogenesis: A narrative review. Iran J Basic Med Sci 2024; 27: 3-11.
75. Kaltsas A, Markou E, Kyrgiafini M-A, Zikopoulos A, Symeonidis EN, Dimitriadis F, et al. Oxidative-stress-mediated epigenetic dysregulation in spermatogenesis: Implications for male infertility and offspring health. Genes (Basel) 2025; 16: 93. [DOI:10.3390/genes16010093] [PMID] [PMCID]
76. Ribo S, Ramon-Krauel M, Palacios-Marin I, Diaz R, Lerin C, Jiménez-Chillarón JC. Epigenetic inheritance of type 2 diabetes. In: Tollefsbol TO. Transgenerational epigenetics. 2nd Ed. USA: Academic Press; 2019. 439-462. [DOI:10.1016/B978-0-12-816363-4.00021-3]
77. Kowluru RA, Kowluru A. Epigenetics of diabetes in humans. In: Tollefsbol TO. Epigenetics in human disease. 3rd Ed. USA: Academic Press; 2024. 491-515. [DOI:10.1016/B978-0-443-18661-5.00009-9]
78. Huang R, Chen J, Guo B, Jiang C, Sun W. Diabetes-induced male infertility: Potential mechanisms and treatment options. Mol Med 2024; 30: 11. [DOI:10.1186/s10020-023-00771-x] [PMID] [PMCID]
79. Saftić Martinović L, Mladenić T, Lovrić D, Ostojić S, Dević Pavlić S. Decoding the epigenetics of infertility: Mechanisms, environmental influences, and therapeutic strategies. Epigenomes 2024; 8: 34. [DOI:10.3390/epigenomes8030034] [PMID] [PMCID]
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