Уровни ретинол-связывающего белка 4 и их связь с липидным профилем у женщин с синдромом поликистозных яичников
DOI:
https://doi.org/10.37800/RM.4.2025.536Ключевые слова:
Синдром поликистозных яичников , С-реактивный белок , дислипидемия, инсулинорезистентностьАннотация
Актуальность: Синдром поликистозных яичников (СПКЯ) является распространённым эндокринным заболеванием, которое часто связано с метаболической дисфункцией. Данное исследование направлено на изучение взаимосвязи ретинол-связывающего белка 4 (RBP4) и С-реактивного белка (CRP) с их сывороточными уровнями у женщин с СПКЯ, а также их корреляции с липидными параметрами. Полученные данные могут быть использованы для определения оптимальных подходов к лечению СПКЯ и связанных с ним метаболических нарушений.
Материалы и методы: В исследование были включены 200 женщин в возрасте от 18 до 40 лет, которые были разделены на четыре группы: 111 худых женщин с СПКЯ, 20 женщин с избыточной массой тела/ожирением без СПКЯ и 69 худых женщин без СПКЯ. Диагноз СПКЯ устанавливался в соответствии с критериями Роттердама. Определялись сывороточные уровни RBP4, CRP и липидных параметров, а также гормональные показатели (свободный тестостерон, антимюллеров гормон и лютеинизирующий гормон). Для оценки инсулинорезистентности использовался индекс HOMA-IR.
Результаты: Уровни RBP4 у женщин с ожирением и СПКЯ были значительно повышены — почти в четыре раза выше по сравнению с худыми женщинами без СПКЯ (184,66 ± 38,20 нг/мл против 75,66 ± 15,05 нг/мл соответственно). Повышенные уровни RBP4 также коррелировали с неблагоприятными изменениями липидного профиля, включая общий холестерин, триглицериды, CRP и увеличение содержания холестерин-насыщенных ЛПОНП. Кроме того, уровни свободного тестостерона, антимюллерова гормона и лютеинизирующего гормона были значительно выше у женщин с СПКЯ; также у них была более выраженная инсулинорезистентность.
Заключение: Изменения уровней RBP4 у женщин с СПКЯ являются значимыми, особенно в связи с повышенным индексом массы тела, и независимо ассоциированы с риском развития дислипидемии и/или метаболических нарушений. RBP4 может рассматриваться как надёжный ранний биомаркер для оценки кардиометаболического риска у женщин с СПКЯ, в контексте метаболических нарушений, часто сопровождающих данное заболевание.
Библиографические ссылки
1. Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocrine reviews. 2016 Oct 1;37(5):467-520.
https://doi.org/10.1210/er.2015-1104
2. Kahsar-Miller MD, Nixon C, Boots LR, Go RC, Azziz R. Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertility and sterility. 2001 Jan 1;75(1):53-8.
https://doi.org/10.1016/S0015-0282(00)01662-9
3. Gu Y, Zhou G, Zhou F, Wu Q, Ma C, Zhang Y, Ding J, Hua K. Life Modifications and PCOS: Old Story But New Tales. Front Endocrinol. 2022;13:808898. https://doi.org/10.3389/fendo.2022.808898
4. Hassan, M. S., Mahdi, H. T., Majed, M. S., Shakir, A. F., Alsafah, A. H., & Alkafaji, N. A. (2025). Physiological Investigation of Lycium Barbarum’s Protective Effects on Reproductive Hormones and Antioxidant Status Against Sodium Dichromate-Induced Toxicity in Male Rats. Natural and Engineering Sciences, 10(1), 393-402. https://doi.org/10.28978/nesciences.1651172
5. Lee S-H, Park S-Y, Choi CS. Insulin Resistance: From Mechanisms to Therapeutic Strategies. Diabetes Metabol J. 2021;46(1):15-37.
https://doi.org/10.4093/dmj.2021.0280
6. Salman, N. A., Al-Noor, S. S., & Khalaf, K. A. (2024). Effect of dose level of three hormones on egg production and thermal accumulated period during induced spawning of grass carp (Ctenopharyngodon idella). International Journal of Aquatic Research and Environmental Studies, 4(1), 1-11. http://doi.org/10.70102/IJARES/V4I1/1
7. Nono Nankam PA, Blüher M. Retinol-binding protein 4 in obesity and metabolic dysfunctions. Mol Cell Endocrinol. 2021;531:111312.https://doi.org/10.1016/j.mce.2021.111312
8. Guo F, Gong Z, Fernando T, Zhang L, Zhu X, Shi Y. The Lipid Profiles in Different Characteristics of Women with PCOS and the Interaction Between Dyslipidemia and Metabolic Disorder States: A Retrospective Study in Chinese Population. Front Endocrinol. 2022;13:892125.
https://doi.org/10.3389/fendo.2022.892125
9. Balamanikandan A, Saravanakumar M, Gunasekaran S, Anjum V, Gurusamy P, Ashokkumar N. Deep learning in the detection of chronic kidney disease. In2023 4th International Conference on Intelligent Technologies (CONIT) 2024 Jun 21 (pp. 1-6). IEEE.
10. Bril F, Ezeh U, Amiri M, Hatoum S, Pace L, Chen Y-H, Bertrand F, Gower B, Azziz R. Adipose Tissue Dysfunction in Polycystic Ovary Syndrome. J Clin Endocrinol Metabol. 2023;109(1):10-24.
11. Aljeboury GH, Risan MH, Algafari RN. Effect of Probiotic Extracted from Lactobacillus Sp. Antagonist Helicobacter pylori of Human Stomach Ulcer. Journal of Global Pharma Technology. 2019;11(05):731-7.
https://doi.org/10.54133/ajms.v5i1s.329
12. Zhao Y, Rao J, Qiu T, Li C, Zhou X. The Effect of RBP4 on microRNA Expression Profiles in Porcine Granulosa Cells. Animals. 2021;11(5):1391.
https://doi.org/10.3390/ani11051391
13. Kadhim RS, Hassan FA. Estimation of Fibulin-1, Chemerin and Omentin-1 in Iraqi Women with Polycystic Ovary Syndrome-Associated Infertility. Al-Rafidain J Med Sci. 2023;5(1S):S125-31
14. Ren Y, Zhao H, Yin C, Lan X, Wu L, Du X, Griffiths HR, Gao D. Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation. Front Endocrinol (Lausanne). 2022;13:873699. https://doi.org/10.3389/fendo.2022.873699
15. Liu Q, Xie Y-j, Qu L-h, Zhang M-x, Mo Z-c. Dyslipidemia involvement in the development of polycystic ovary syndrome. Taiwan J Obstet Gynecol. 2019;58(4):447-53.
https://doi.org/10.1016/j.tjog.2019.05.003
16. Mahboobifard F, Rahmati M, Amiri M, Azizi F, Ramezani Tehrani F. To what extent does polycystic ovary syndrome influence the cut-off value of Prolactin? Findings of a community-based study. Adv Medical Sci. 2022;67(1):79-86.
https://doi.org/10.1016/j.advms.2021.12.003
17. Mahmood, A. H., Al-Awadi, S. J., Al-Attar, M. M., Alshammary, R. A. A., & Abood, R. S. (2024). Investigate the association between genetic polymorphisms of ACE and ACE-2 with some biomarkers in Iraqi patients with COVID-19. Human Gene, 42, Article 201344. https://doi.org/10.1016/j.humgen.2024.201344.
18. Zhang B, Zhan Z, Xi S, Wang F, Yuan X. Impact of serum retinol-binding protein 4 levels in late pregnancy on the incidence of small/large for gestational age infants among 11,854 pregnant women: A retrospective study. J Epidemiol. 2025;35(6):287-296. https://doi.org/10.2188/jea.JE20240275
19. Amadi CF, Okolonkwo BN, George-Oparati MI, Odiabara KK. Understanding the relationship between polycystic ovarian syndrome (PCOS) and dyslipidemia. Asian J Biochem Genet Mol Biol. 2023;15(3):1-11.
https://doi.org/10.9734/AJBGMB/2023/v15i3333
20. Al-Qaisi SMA, Al-Shammaa NMJ. Effect of Anti Mullerian Hormone (AMH) on Hyperthyroidism with and without polycystic ovarian syndrome (PCOS) in female patients. Iraqi J Sci. 2021;58(4A):1808-14.
https://doi.org/10.24996/ijs.2017.58.4A.4
21. Tahapary DL, Pratisthita LB, Fitri NA, Marcella C, Wafa S, Kurniawan F, Rizka A, Tarigan TJE, Harbuwono DS, Purnamasari D, Soewondo P. Challenges in the diagnosis of insulin resistance: Focusing on the role of HOMA-IR and Tryglyceride/glucose index. Diabetes Metabolic Syndrome: Clin Res Rev. 2022;16(8):102581.
https://doi.org/10.1016/j.dsx.2022.102581
22. Arvanitis M, Lowenstein CJ. Dyslipidemia. Ann Intern Med. 2023;176(6):ITC81-ITC96.
https://doi.org/10.7326/AITC202306200
23. Barber TM, Franks S. Obesity and polycystic ovary syndrome. Clin Endocrinol. 2021;95(4):531-541.
https://doi.org/10.1111/cen.14421
24. Nussbaumerova B, Rosolova H. Obesity and Dyslipidemia. Curr Atherosclerosis Rep. 2023;25(12):947-955. https://doi.org/10.1007/s11883-023-01167-2
25. Lee S-H, Park S-Y, Choi CS. Insulin Resistance: From Mechanisms to Therapeutic Strategies. Diabetes Metabol J. 2021;46(1):15-37.
https://doi.org/10.4093/dmj.2021.0280
26. Merza WM, Yaseen AK, Mahmood MA. FSH, LH, lipid and adipokines in Polycystic Ovary Syndrome: Clinical biochemistry insights for diagnosis and management. J Steroid Biochem Mol Biol. 2025;251:106773.
https://doi.org/10.1016/j.jsbmb.2025.106773
27. Mastnak L, Herman R, Ferjan S, Janež A, Jensterle M. Prolactin in Polycystic Ovary Syndrome: Metabolic Effects and Therapeutic Prospects. Life. 2023;13(11):2124. https://doi.org/10.3390/life13112124
28. Zheng Y, Yin G, Chen F, Lin L, Chen Y. Evaluation of triglyceride glucose index and homeostasis model of insulin resistance in patients with polycystic ovary syndrome. Int J Women’s Health. 2022;14:1821-1829.
https://doi.org/10.2147/IJWH.S387942
29. Mitrašinović-Brulić M, Buljan M, Suljević D. Association of LH/FSH ratio with menstrual cycle regularity and clinical features of patients with polycystic ovary syndrome. MiddLe East Fertil Soc J. 2021;26(1):40. https://doi.org/10.1186/s43043-021-00085-0
30. Alkhaleeli ABM. Hormonal Profile Changes as A predictive Marker for Polycystic Ovary Syndrome and Infertility in Women. Pure Sci Int J Kerbala. 2024;1(4):64-69. https://journals.uokerbala.edu.iq/index.php/psijk/article/view/2692
31. Yeh ETH. CRP as a Mediator of Disease. Circulation. 2004;109(21 Suppl 1), II11–II14.
https://doi.org/10.1161/01.CIR.0000129507.12719.80
32. Leca BM, Kite C, Lagojda L, Davasgaium A, Dallaway A, Chatha KK, Randeva HS, Kyrou I. Retinol-binding protein 4 (RBP4) circulating levels and gestational diabetes mellitus: a systematic review and meta-analysis. Front Public Health. 2024;12:1348970. https://doi.org/10.3389/fpubh.2024.1348970
33. Yao J-M, Ying H-Z, Zhang H-H, Qiu F-S, Wu J-Q, Yu C-H. Exosomal RBP4 potentiated hepatic lipid accumulation and inflammation in high-fat-diet-fed mice by promoting M1 polarization of Kupffer cells. Free Rad Biol Med. 2023;195:58-73. https://doi.org/10.1016/j.freeradbiomed.2022.12.085
34. Mansour A, Mirahmad M, Mohajeri-Tehrani MR, Jamalizadeh M, Hosseinimousa S, Rashidi F, Asili P, Sajjadi-Jazi SM. Risk factors for insulin resistance related to polycystic ovarian syndrome in Iranian population. Sci Rep. 2023;13(1):10269. https://doi.org/10.1038/s41598-023-37513-2
35. Taghizadeh N, Mohammadi S, Saeedi V, Haghighi L, Nourbakhsh M, Nourbakhsh M, Nourbakhsh M, Azar MR. Association between steroid hormones and insulin resistance in patients with polycystic ovary syndrome. Acta Biochim Iran. 2023 Nov 15. https://doi.org/10.18502/abi.v1i1.14062
36. Frances L, Tavernier G, Viguerie N. Adipose-Derived Lipid-Binding Proteins: The Good, the Bad and the Metabolic Diseases. Int J Mol Sci. 2021;22(19):10460. https://doi.org/10.3390/ijms221910460
37. Capuzzo M, La Marca A. Use of AMH in the Differential Diagnosis of Anovulatory Disorders Including PCOS. Front Endocrinol. 2021;11:616766.
https://doi.org/10.3389/fendo.2020.616766
38. Malhotra N, Mahey R, Cheluvaraju R, Rajasekaran K, Patkar D, Prabhakar P, Rajput M, Upadhyay A. Serum Anti-Mullerian Hormone (AMH) Levels Among Different PCOS Phenotypes and Its Correlation with Clinical, Endocrine, and Metabolic Markers of PCOS. Reprod Sci. 2023;30(8):2554-2562. https://doi.org/10.1007/s43032-023-01195-y
39. Christ JP, Cedars MI. Current Guidelines for Diagnosing PCOS. Diagnostics. 2023;13(6):1113. https://doi.org/10.3390/diagnostics13061113
40. Nono Nankam PA, Blüher M. Retinol-binding protein 4 in obesity and metabolic dysfunctions. Mol Cell Endocrinol. 2021;531:111312.https://doi.org/10.1016/j.mce.2021.111312
41. Sahana Devi, K. J., & Yendapalli, V. (2025). Advanced Neural Decision Tree Paradigm for Proactive Detection and Precision Prediction of Polycystic Ovary Syndrome. Journal of Wireless Mobile Networks, Ubiquitous Computing, and Dependable Applications, 16(1), 576-598. https://doi.org/10.58346/JOWUA.2025.I1.034
42. Gilani A, Stoll L, Homan EA, Lo JC. Adipose Signals Regulating Distal Organ Health and Disease. Diabetes. 2024;73(2):169-177. https://doi.org/10.2337/dbi23-0005
10. Bril F, Ezeh U, Amiri M, Hatoum S, Pace L, Chen Y-H, Bertrand F, Gower B, Azziz R. Adipose Tissue Dysfunction in Polycystic Ovary Syndrome. J Clin Endocrinol Metabol. 2023;109(1):10-24.
https://doi.org/10.1210/clinem/dgad356
11. Aljeboury GH, Risan MH, Algafari RN. Effect of Probiotic Extracted from Lactobacillus Sp. Antagonist Helicobacter pylori of Human Stomach Ulcer. J Glob Pharma Technol. 2019;11(05):731-7.
https://doi.org/10.54133/ajms.v5i1s.329
12. Zhao Y, Rao J, Qiu T, Li C, Zhou X. The Effect of RBP4 on microRNA Expression Profiles in Porcine Granulosa Cells. Animals. 2021;11(5):1391.
https://doi.org/10.3390/ani11051391
13. Kadhim RS, Hassan FA. Estimation of Fibulin-1, Chemerin and Omentin-1 in Iraqi Women with Polycystic Ovary Syndrome-Associated Infertility. Al-Rafidain J Med Sci. 2023;5(1S):S125-31
https://doi.org/10.54133/ajms.v5i1S.329
14. Ren Y, Zhao H, Yin C, Lan X, Wu L, Du X, Griffiths HR, Gao D. Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation. Front Endocrinol (Lausanne). 2022;13:873699. https://doi.org/10.3389/fendo.2022.873699
15. Liu Q, Xie Y-j, Qu L-h, Zhang M-x, Mo Z-c. Dyslipidemia involvement in the development of polycystic ovary syndrome. Taiwan J Obstet Gynecol. 2019;58(4):447-53.
https://doi.org/10.1016/j.tjog.2019.05.003
16. Mahboobifard F, Rahmati M, Amiri M, Azizi F, Ramezani Tehrani F. To what extent does polycystic ovary syndrome influence the cut-off value of Prolactin? Findings of a community-based study. Adv Medical Sci. 2022;67(1):79-86.
https://doi.org/10.1016/j.advms.2021.12.003
17. Mahmood, A. H., Al-Awadi, S. J., Al-Attar, M. M., Alshammary, R. A. A., & Abood, R. S. (2024). Investigate the association between genetic polymorphisms of ACE and ACE-2 with some biomarkers in Iraqi patients with COVID-19. Human Gene, 42, Article 201344.
https://doi.org/10.1016/j.humgen.2024.201344
18. Zhang B, Zhan Z, Xi S, Wang F, Yuan X. Impact of serum retinol-binding protein 4 levels in late pregnancy on the incidence of small/large for gestational age infants among 11,854 pregnant women: A retrospective study. J Epidemiol. 2025;35(6):287-296. https://doi.org/10.2188/jea.JE20240275
19. Amadi CF, Okolonkwo BN, George-Oparati MI, Odiabara KK. Understanding the relationship between polycystic ovarian syndrome (PCOS) and dyslipidemia. Asian J Biochem Genet Mol Biol. 2023;15(3):1-11.
https://doi.org/10.9734/AJBGMB/2023/v15i3333
20. Al-Qaisi SMA, Al-Shammaa NMJ. Effect of Anti Mullerian Hormone (AMH) on Hyperthyroidism with and without polycystic ovarian syndrome (PCOS) in female patients. Iraqi J Sci. 2021;58(4A):1808-14.
https://doi.org/10.24996/ijs.2017.58.4A.4
21. Tahapary DL, Pratisthita LB, Fitri NA, Marcella C, Wafa S, Kurniawan F, Rizka A, Tarigan TJE, Harbuwono DS, Purnamasari D, Soewondo P. Challenges in the diagnosis of insulin resistance: Focusing on the role of HOMA-IR and Tryglyceride/glucose index. Diabetes Metabolic Syndrome: Clin Res Rev. 2022;16(8):102581.
https://doi.org/10.1016/j.dsx.2022.102581
22. Arvanitis M, Lowenstein CJ. Dyslipidemia. Ann Intern Med. 2023;176(6):ITC81-ITC96.
https://doi.org/10.7326/AITC202306200
23. Barber TM, Franks S. Obesity and polycystic ovary syndrome. Clin Endocrinol. 2021;95(4):531-541.
https://doi.org/10.1111/cen.14421
24. Nussbaumerova B, Rosolova H. Obesity and Dyslipidemia. Curr Atherosclerosis Rep. 2023;25(12):947-955. https://doi.org/10.1007/s11883-023-01167-2
25. Lee S-H, Park S-Y, Choi CS. Insulin Resistance: From Mechanisms to Therapeutic Strategies. Diabetes Metabol J. 2021;46(1):15-37.
https://doi.org/10.4093/dmj.2021.0280
26. Merza WM, Yaseen AK, Mahmood MA. FSH, LH, lipid and adipokines in Polycystic Ovary Syndrome: Clinical biochemistry insights for diagnosis and management. J Steroid Biochem Mol Biol. 2025;251:106773.
https://doi.org/10.1016/j.jsbmb.2025.106773
27. Mastnak L, Herman R, Ferjan S, Janež A, Jensterle M. Prolactin in Polycystic Ovary Syndrome: Metabolic Effects and Therapeutic Prospects. Life. 2023;13(11):2124. https://doi.org/10.3390/life13112124
28. Zheng Y, Yin G, Chen F, Lin L, Chen Y. Evaluation of triglyceride glucose index and homeostasis model of insulin resistance in patients with polycystic ovary syndrome. Int J Women’s Health. 2022;14:1821-1829.
https://doi.org/10.2147/IJWH.S387942
29. Mitrašinović-Brulić M, Buljan M, Suljević D. Association of LH/FSH ratio with menstrual cycle regularity and clinical features of patients with polycystic ovary syndrome. MiddLe East Fertil Soc J. 2021;26(1):40. https://doi.org/10.1186/s43043-021-00085-0
30. Alkhaleeli ABM. Hormonal Profile Changes as A predictive Marker for Polycystic Ovary Syndrome and Infertility in Women. Pure Sci Int J Kerbala. 2024;1(4):64-69. https://journals.uokerbala.edu.iq/index.php/psijk/article/view/2692
31. Yeh ETH. CRP as a Mediator of Disease. Circulation. 2004;109(21 Suppl 1), II11–II14.
https://doi.org/10.1161/01.CIR.0000129507.12719.80
32. Leca BM, Kite C, Lagojda L, Davasgaium A, Dallaway A, Chatha KK, Randeva HS, Kyrou I. Retinol-binding protein 4 (RBP4) circulating levels and gestational diabetes mellitus: a systematic review and meta-analysis. Front Public Health. 2024;12:1348970. https://doi.org/10.3389/fpubh.2024.1348970
33. Yao J-M, Ying H-Z, Zhang H-H, Qiu F-S, Wu J-Q, Yu C-H. Exosomal RBP4 potentiated hepatic lipid accumulation and inflammation in high-fat-diet-fed mice by promoting M1 polarization of Kupffer cells. Free Rad Biol Med. 2023;195:58-73. https://doi.org/10.1016/j.freeradbiomed.2022.12.085
34. Mansour A, Mirahmad M, Mohajeri-Tehrani MR, Jamalizadeh M, Hosseinimousa S, Rashidi F, Asili P, Sajjadi-Jazi SM. Risk factors for insulin resistance related to polycystic ovarian syndrome in Iranian population. Sci Rep. 2023;13(1):10269. https://doi.org/10.1038/s41598-023-37513-2
35. Taghizadeh N, Mohammadi S, Saeedi V, Haghighi L, Nourbakhsh M, Nourbakhsh M, Nourbakhsh M, Azar MR. Association between steroid hormones and insulin resistance in patients with polycystic ovary syndrome. Acta Biochim Iran. 2023 Nov 15. https://doi.org/10.18502/abi.v1i1.14062
36. Frances L, Tavernier G, Viguerie N. Adipose-Derived Lipid-Binding Proteins: The Good, the Bad and the Metabolic Diseases. Int J Mol Sci. 2021;22(19):10460. https://doi.org/10.3390/ijms221910460
37. Capuzzo M, La Marca A. Use of AMH in the Differential Diagnosis of Anovulatory Disorders Including PCOS. Front Endocrinol. 2021;11:616766.
https://doi.org/10.3389/fendo.2020.616766
38. Malhotra N, Mahey R, Cheluvaraju R, Rajasekaran K, Patkar D, Prabhakar P, Rajput M, Upadhyay A. Serum Anti-Mullerian Hormone (AMH) Levels Among Different PCOS Phenotypes and Its Correlation with Clinical, Endocrine, and Metabolic Markers of PCOS. Reprod Sci. 2023;30(8):2554-2562.
https://doi.org/10.1007/s43032-023-01195-y
39. Christ JP, Cedars MI. Current Guidelines for Diagnosing PCOS. Diagnostics. 2023;13(6):1113.
https://doi.org/10.3390/diagnostics13061113
40. Nono Nankam PA, Blüher M. Retinol-binding protein 4 in obesity and metabolic dysfunctions. Mol Cell Endocrinol. 2021;531:111312.
https://doi.org/10.1016/j.mce.2021.111312
41. Sahana Devi KJ, Yendapalli V. Advanced Neural Decision Tree Paradigm for Proactive Detection and Precision Prediction of Polycystic Ovary Syndrome. J Wirel Mob Netw Ubiquitous Comput Dependable Appl. 2025;16(1):576-598.
https://doi.org/10.58346/JOWUA.2025.I1.034
42. Gilani A, Stoll L, Homan EA, Lo JC. Adipose Signals Regulating Distal Organ Health and Disease. Diabetes. 2024;73(2):169-177.
Загрузки
Опубликован
Как цитировать
Выпуск
Раздел
Лицензия
Copyright (c) 2025 Hussein Ali Athraa, Mahmoud Nsaif Zahraa
Это произведение доступно по лицензии Creative Commons «Attribution-NonCommercial-NoDerivatives» («Атрибуция — Некоммерческое использование — Без производных произведений») 4.0 Всемирная.
Публикуемые в этом журнале статьи размещены под лицензией CC BY-NC-ND 4.0 (Creative Commons Attribution — Non Commercial — No Derivatives 4.0 International), которая предусматривает только их некоммерческое использование. В соответствии с этой лицензией пользователи имеют право копировать и распространять материалы, охраняемые авторским правом, но им не разрешается изменять или использовать их в коммерческих целях. Полная информация о лицензировании доступна по адресу https://creativecommons.org/licenses/by-nc-nd/4.0/.
