العلاقة البيوكيميائية بين البروينكيفالين والأمراض المزمنة

REFERENCES

1. Abrimian, A., Kraft, T., & Pan, Y.-X. (2021). Endogenous opioid peptides and alternatively spliced mu opioid receptor seven transmembrane carboxyl-terminal variants. International Journal of Molecular Sciences, 22(7), 3779. https://doi.org/10.3390/ijms22073779 ⁠

2. Abu-Rumeileh, S., Barschke, P., Oeckl, P., Baiardi, S., Mammana, A., Mastrangelo, A., Al Shweiki, M. R., Steinacker, P., Ladogana, A., Capellari, S., Otto, M., & Parchi, P. (2022). Prodynorphin and proenkephalin in cerebrospinal fluid of sporadic Creutzfeldt–Jakob disease. International Journal of Molecular Sciences, 23(4), 2051. https://doi.org/10.3390/ijms23042051 ⁠

3. Abubakar, M. Z., Abdulsalam, K., & Yahaya, I. A. (2020). Thyroid hormones profile of patients with type 2 diabetes mellitus in Kano, Nigeria. Annals of African Medical Research, 3(1). https://doi.org/10.4081/aamr.2020.112 ⁠

4. Akgün, E., Lunzer, M. M., Tian, D., Ansonoff, M., Pintar, J., Bruce, D., Hawkinson, J. E., Wilcox, G. L., & Portoghese, P. S. (2021). FBNTI, a DOR-selective antagonist that allosterically activates MOR within a MOR-DOR heteromer. Biochemistry, 60(18), 1413–1419. https://doi.org/10.1021/acs.biochem.0c00498 ⁠

5. Angulo, J. A., Ledoux, M., & McEwen, B. S. (1991). Chronic treatment with pentazocine or SFK 10047 decrease proenkephalin mRNA levels in the rat striatum and nucleus accumbens. Neuroscience Letters, 122(1), 47–49. https://doi.org/10.1016/0304-3940(91)90189-z ⁠

6. Arlt, B., Caironi, P., Meessen, J., et al. (2026). Clinical utility of proenkephalin A 119–159 for prediction of worsening renal function and prognosis in patients with sepsis – Results of a patient-level meta-analysis. Critical Care, 30, 164. https://doi.org/10.1186/s13054-026-05947-5 ⁠

7. Assis, M. A., Carranza, P. G., & Ambrosio, E. (2021). A “drug-dependent” immune system can compromise protection against infection: The relationships between psychostimulants and HIV. Viruses, 13(5), 722. https://doi.org/10.3390/v13050722 ⁠

13-Matsiras, D., Ventoulis, I., Verras, C., et al. (2025). Proenkephalin 119–159 in heart failure: From pathophysiology to clinical implications. Journal of Clinical Medicine. https://www.sciencedirect.com/science/article/pii/S0009912018300389 ⁠

8. Badr, H., Shaban, M., & Gazala, E. (2023). Thyroid diseases as a risk of type 2 diabetes mellitus. Menoufia Medical Journal, 36. https://doi.org/10.59204/2314-6788.1035 ⁠

9. Banerjee, S., Garimella, P. S., Hong, K. N., Bullen, A. L., Daniels, L. B., & Wettersten, N. (2024). Association between proenkephalin A and cardiovascular outcomes in ambulatory veterans. International Journal of Cardiology: Heart & Vasculature, 55, 101557. https://doi.org/10.1016/j.ijcha.2024.101557 ⁠

10. Beunders, R., van Groenendael, R., Leijte, G. P., Kox, M., & Pickkers, P. (2020). Proenkephalin compared to conventional methods to assess kidney function in critically ill sepsis patients. Shock, 54(3), 308–314. https://doi.org/10.1097/SHK.0000000000001510

11. Bergasa, N. V., Vergalla, J., Swain, M. G., & Jones, E. A. (1996). Hepatic concentrations of proenkephalin-derived opioids are increased in a rat model of cholestasis. Liver, 16(5), 298–302. https://doi.org/10.1111/j.1600-0676.1996.tb00749.x

12. B. M., & Terdal, S. (2024). Artificial intelligence for early-stage detection of chronic kidney disease. International Journal of Electrical and Computer Engineering, 14(4), 4775–4790. https://doi.org/10.11591/ijece.v14i4.pp4775-4790 ⁠

13. Bodnar, R. J. (2025). Endogenous opiates and behavior: 2024. Peptides, 191, 171422. https://doi.org/10.1016/j.peptides.2025.171422

14. Boyella, V. D., Nicastri, A. D., & Bergasa, N. V. (2008). Human hepatic met-enkephalin and delta opioid receptor-1 immunoreactivities in viral and autoimmune hepatitis. Annals of Hepatology, 7(3), 221–226. https://doi.org/10.1016/S1665-2681(19)31851-4

15. Chakrabarti, S., Liu, N. J., & Gintzler, A. R. (2021). Relevance of mu-opioid receptor splice variants and plasticity of their signaling sequelae to opioid analgesic tolerance. Cellular and Molecular Neurobiology, 41(5), 855–862. https://doi.org/10.1007/s10571-020-00934-y

16. Conibear, A. C. (2020). Deciphering protein post-translational modifications using chemical biology tools. Nature Reviews Chemistry, 4, 674–695. https://doi.org/10.1038/s41570-020-00223-8

17. Corder, G., Castro, D. C., Bruchas, M. R., & Scherrer, G. (2018). Endogenous and exogenous opioids in pain. Annual Review of Neuroscience, 41, 453–473. https://doi.org/10.1146/annurev-neuro-080317-061522

18. Cullen, J. M., & Cascella, M. (2023). Physiology, enkephalin. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK557764/

19. Dalefield, M. L., Scouller, B., Bibi, R., & Kivell, B. M. (2022). The kappa opioid receptor: A promising therapeutic target for multiple pathologies. Frontiers in Pharmacology, 13, 837671. https://doi.org/10.3389/fphar.2022.837671

20. Elnagar, G. M., Elseweidy, M. M., Mahmoud, Y. K., Elkomy, N. M. I. M., Althafar, Z. M., Alnomasy, S. F., Al-Gabri, N. A., & Shawky, M. (2022). 10-Dehydrogingerdione attenuates tramadol-induced nephrotoxicity by modulating renal oxidative stress, inflammation and apoptosis in experimental rats: Role of HO-1 activation and TLR4/NF-κB/ERK inhibition. International Journal of Molecular Sciences, 23(3), 1384. https://doi.org/10.3390/ijms23031384

21. Emmens, J. E., ter Maaten, J. M., Brouwers, F. P., et al. (2021). Proenkephalin and the risk of new-onset heart failure: Data from prevention of renal and vascular end-stage disease. Clinical Cardiology, 44(12), 1662–1672. https://doi.org/10.1002/clc.23729

22. Emmens, J. E., ter Maaten, J. M., Damman, K., et al. (2019). Proenkephalin, an opioid system surrogate, as a novel comprehensive renal marker in heart failure. Circulation: Heart Failure, 12(5), e005544. https://doi.org/10.1161/CIRCHEARTFAILURE.118.005544

23. Farag, M., et al. (2025). Cerebrospinal fluid proenkephalin predicts striatal atrophy decades before clinical motor diagnosis in Huntington's disease. Movement Disorders, 41, 95–106. https://doi.org/10.1002/mds.70062

24. Fricker, L. D., Margolis, E. B., Gomes, I., & Devi, L. A. (2020). Five decades of research on opioid peptides: Current knowledge and unanswered questions. Molecular Pharmacology, 98(2), 96–108. https://doi.org/10.1124/mol.120.119388

25. Gaborit, M., & Massotte, D. (2023). Therapeutic potential of opioid receptor heteromers in chronic pain and associated comorbidities. British Journal of Pharmacology, 180(7), 994–1013. https://doi.org/10.1111/bph.15772

26. Gao, S., & He, Q. (2024). Opioids and the kidney: Two sides of the same coin. Frontiers in Pharmacology, 15, 1421248. https://doi.org/10.3389/fphar.2024.1421248 ⁠

27. García-Domínguez, M. (2024). Enkephalins and pain modulation: Mechanisms of action and therapeutic perspectives. Biomolecules, 14(8), 926. https://doi.org/10.3390/biom14080926

28. Grycuk, W., Jakubowska, Z., & Małyszko, J. (2023). Proenkephalin levels and its determinants in patients with end-stage kidney disease treated with hemodialysis and peritoneal dialysis. International Journal of Molecular Sciences, 24(19), 15015. https://doi.org/10.3390/ijms241915015

29. Grycuk, W., Jakubowska, Z., & Małyszko, J. (2025). Proenkephalin (PENK): A functional biomarker in chronic kidney diseases—Hope or just a new bystander? Journal of Nephrology, 38(7), 1785–1795. https://doi.org/10.1007/s40620-025-02268-8

30. -Hassoun, M. A., & Abass, E. A. (2025). Proenkephalin-A as a biomarker for type 2 diabetes in women with thyroid disorders. Journal of the Faculty of Medicine Baghdad, 67(3), 395–402. https://doi.org/10.32007/jfacmedbaghdad3162

31. Huang, N. (2025, October). Opioid receptor agonists in dermatology. DermNet NZ. Reviewed by I. Coulson. https://dermnetnz.org/topics/opioid-receptor-agonists-in-dermatology ⁠

32. JACC. (n.d.). Figure from study. https://www.jacc.org/cms/asset/ebe6c694-7bab-452e-a7d5-9c8d18b608be/fx1.jpg ⁠

33. Kanagala, P., Squire, I. B., Jones, D. J. L., et al. (2019). Proenkephalin and prognosis in heart failure with preserved ejection fraction: A GREAT network study. Clinical Research in Cardiology, 108(8), 940–949. https://doi.org/10.1007/s00392-019-01424-y ⁠

34. Karavitaki, N., Bettinger, J. J., Biermasz, N., Christ-Crain, M., Gadelha, M. R., Inder, W. J., Tsourdi, E., Wakeman, S. E., & Zatelli, M. (2024). Exogenous opioids and the human endocrine system: An Endocrine Society scientific statement. Endocrine Reviews, 45(6), 773–794. https://doi.org/10.1210/endrev/bnae023 ⁠

35. Khorashadi, M., Beunders, R., Pickkers, P., & Legrand, M. (2020). Proenkephalin: A new biomarker for glomerular filtration rate and acute kidney injury. Nephron, 144(12), 655–661. https://doi.org/10.1159/000509352

36. Konradi, C., Macías, W., Dudman, J. T., & Carlson, R. R. (2003). Striatal proenkephalin gene induction: Coordinated regulation by cyclic AMP and calcium pathways. Molecular Brain Research, 115(2), 157–161. https://doi.org/10.1016/S0169-328X(03)00204-3

37. Kumar, R., Saha, P., Kumar, Y., Sahana, S., Dubey, A., & Prakash, O. (2020). A review on diabetes mellitus: Type 1 & Type 2. World Journal of Pharmaceutical and Pharmaceutical Sciences, 9, 838–850. https://doi.org/10.20959/wjpps202010-17336

38. Lin, L.-C., Chuan, M.-H., Liu, J.-H., et al. (2023). Proenkephalin as a biomarker correlates with acute kidney injury: A systematic review with meta-analysis and trial sequential analysis. Critical Care, 27, 481. https://doi.org/10.1186/s13054-023-04747-5

39. Liu, C., Liu, X., He, Z., et al. (2023). Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration. Nature Communications, 14, 7167. https://doi.org/10.1038/s41467-023-42929-5 ⁠

40. López-Campos, J. L., Gutiérrez, C., & Calero, C. (2012). The potential role of racecadotril in the treatment of diarrhea associated with roflumilast. Archivos de Bronconeumología, 48(11), 426. https://doi.org/10.1016/j.arbr.2012.08.001

41. Machelska, H., & Celik, M. Ö. (2020). Opioid receptors in immune and glial cells—Implications for pain control. Frontiers in Immunology, 11, 300. https://doi.org/10.3389/fimmu.2020.00300

42. Martin, L., Martin, C., Peine, A., Imöhl, M., Kersten, A., Kramann, R., Saritas, T., Marx, N., Dreher, M., Marx, G., & Simon, T. P. (2025). Implementation and one-year evaluation of proenkephalin A in critical care. International Journal of Molecular Sciences, 26(6), 2602. https://doi.org/10.3390/ijms26062602 ⁠

43. Matsiras, D., Ventoulis, I., Verras, C., et al. (2025). Proenkephalin 119-159 in heart failure: From pathophysiology to clinical implications. Journal of Clinical Medicine, 14(8), 2657. https://doi.org/10.3390/jcm14082657

44. Maytum, A., Obier, N., Cauchy, P., & Bonifer, C. (2024). Regulation of developmentally controlled enhancer activity by extrinsic signals in normal and malignant cells: AP-1 at the centre. Frontiers in Epigenetics and Epigenomics, 2, 1465958. https://doi.org/10.3389/freae.2024.1465958

45. Mori, T., Ohya, J., Itoh, T., Ise, Y., Shibasaki, M., & Suzuki, T. (2015). Effects of (+)-pentazocine on the antinociceptive effects of (−)-pentazocine in mice. Synapse, 69(3), 166–171. https://doi.org/10.1002/syn.21799 ⁠

46. Oliveira, C. L., Duarte-Ramos, F., Alves da Costa, F., et al. (2024). Effects of inpatient creatinine testing frequency on acute kidney injury identification and staging: A historical cohort study. International Journal of Clinical Pharmacy, 46, 623–630. https://doi.org/10.1007/s11096-023-01697-4 ⁠

47. Pottel, H., Delanaye, P., & Cavalier, E. (2024). Exploring renal function assessment: Creatinine, cystatin C, and estimated glomerular filtration rate focused on the European Kidney Function Consortium equation. Annals of Laboratory Medicine, 44(2), 135–143. https://doi.org/10.3343/alm.2023.0237

48. Primary response gene expression in the nervous system. (2010). In Neurotrophic Factors (Vol. 4, pp. 89–128). Academic Press. https://doi.org/10.1016/B978-0-08-057132-4.50008-3 ⁠

49. Puri, C., Dannenberg, C., Ucci, A., et al. (2024). Pre-proenkephalin 1 is downregulated under unloading and is involved in osteoblast biology. Calcified Tissue International, 114(5), 524–534. https://doi.org/10.1007/s00223-024-01199-z ⁠

50. Qiu, Y., & Wang, Y.-J. (2024). Editorial: Opioids and opioid receptors in pain, addiction, and mood disorders. Frontiers in Psychiatry, 15, 1382894. https://doi.org/10.3389/fpsyt.2024.1382894 ⁠

51. Quirion, B., Bergeron, F., Blais, V., & Gendron, L. (2020). The delta-opioid receptor; a target for the treatment of pain. Frontiers in Molecular Neuroscience, 13, 52. https://doi.org/10.3389/fnmol.2020.00052 ⁠

52. Rau, M., Kurt, B., Hartmann, O., et al. (2024). Proenkephalin A 119–159 (penKid) and mortality in stable patients at high cardiovascular risk. Clinical Kidney Journal, 17(9), sfae246. https://doi.org/10.1093/ckj/sfae246 ⁠

53. Safdar, A., Akram, W., Khan, M. A., & Muhammad, S. (2023). Optimal glomerular filtration rate equations for various age groups, disease conditions and ethnicities in Asia: A systematic review. Journal of Clinical Medicine, 12(5), 1822. https://doi.org/10.3390/jcm12051822 ⁠

54. Santa Cruz Biotechnology. (n.d.). Proenkephalin A activators. https://www.scbt.com ⁠

55. Schulte, J., Dépret, F., Hartmann, O., Pickkers, P., & Laterre, P. F. (2024). Clinical performance of proenkephalin A 119–159 for the early diagnosis of acute kidney injury in patients with sepsis or septic shock. medRxiv. https://doi.org/10.1101/2024.10.11.24315291

56. Shenoy, S. S., & Lui, F. (2023). Biochemistry, endogenous opioids. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK532899 ⁠

57. Siranart, N., Laohasurayotin, K., Phanthong, T., Sowalertrat, W., Ariyachaipanich, A., & Chokesuwattanaskul, R. (2023). Proenkephalin as a novel prognostic marker in heart failure patients: A systematic review and meta-analysis. International Journal of Molecular Sciences, 24(5), 4887. https://doi.org/10.3390/ijms24054887 ⁠

58. Ślusarz, M. J. (2022). Molecular insights into the mechanism of sugar-modified enkephalin binding to opioid receptors. Computational Biology and Chemistry, 101, 107783. https://doi.org/10.1016/j.compbiolchem.2022.107783 ⁠

59. Sobocińska, M., Giełdoń, A., Fichna, J., & Kamysz, E. (2019). 1-Substituted sialorphin analogues—Synthesis, molecular modelling and in vitro effect on enkephalins degradation by NEP. Amino Acids, 51, 1201–1207. https://doi.org/10.1007/s00726-019-02760-z ⁠

60. Soetedjo, N. N. M., Agustini, D., & Permana, H. (2024). The impact of thyroid disorder on cardiovascular disease: Unraveling the connection and implications for patient care. International Journal of Cardiology: Heart & Vasculature, 55, 101536. https://doi.org/10.1016/j.ijcha.2024.101536 ⁠

61. Southerland, W. A., Gillis, J., Kuppalli, S., Fonseca, A., Mendelson, A., Horine, S. V., Bansal, N., & Gulati, A. (2021). Dual enkephalinase inhibitors and their role in chronic pain management. Current Pain and Headache Reports, 25(5), 29. https://doi.org/10.1007/s11916-021-00949-0 ⁠

62. Spetea, M., & Schmidhammer, H. (2020). Opioids and their receptors: Present and emerging concepts in opioid drug discovery. Molecules, 25(23), 5658. https://doi.org/10.3390/molecules25235658 ⁠

63. Szentkirályi-Tóth, S., et al. (2023). Estrogen-regulated peptidergic input to gonadotropin-releasing hormone neurons from the lateral septal kisspeptin network. bioRxiv. https://doi.org/10.1101/2023.09.20.557932 ⁠

64. Walczak-Wieteska, P., Zuzda, K., Małyszko, J., & Andruszkiewicz, P. (2024). Proenkephalin A 119–159 in perioperative and intensive care—A promising biomarker or merely another option? Diagnostics, 14(21), 2364, 1–18. https://doi.org/10.3390/diagnostics14212364 ⁠

65. Walczak-Wieteska, P., Zuzda, K., Małyszko, J., et al. (2025). Proenkephalin A 119–159 as an early biomarker of acute kidney injury in complex endovascular aortic repair: An explorative single-center cross-sectional study with the utilization of two measurement methods. Perioperative Medicine, 14(1), 66. https://doi.org/10.1186/s13741-025-00553-5 ⁠

66. Wang, Y., Zhuang, Y., DiBerto, J. F., Zhou, X. E., Schmitz, G. P., Yuan, Q., Jain, M. K., Liu, W., Melcher, K., Jiang, Y., Roth, B. L., & Xu, H. E. (2023). Structures of the entire human opioid receptor family. Cell, 186(2), 413–427.e17. https://doi.org/10.1016/j.cell.2022.12.026 ⁠

67. Voors, A. A., ter Maaten, J. M., Damman, K., et al. (2017). Proenkephalin, an opioid system surrogate, as a novel comprehensive renal marker in heart failure. Journal of the American College of Cardiology, 69(11), 1499–1509. https://doi.org/10.1016/j.jacc.2016.12.039 ⁠

68. Zhu, T., Li, C., & Chu, X. (2024). Fluctuating chromatin facilitates enhancer–promoter communication by regulating transcriptional clustering dynamics. The Journal of Physical Chemistry Letters. https://doi.org/10.1021/acs.jpclett.4c02453