ORIGINAL RESEARCH
General Surgery
doi: 10.25005/2074-0581-2025-27-4-890-898
CLINICAL AND IMMUNOLOGICAL PARALLELS IN LONG-TERM NON-HEALING WOUNDS OF PATIENTS WITH DIABETES MELLITUS

T.U. ARIPOVA1, A.O. OKHUNOV2, B.YA. UMAROV3, B.Z. KHAMDAMOV4

1Institute of Immunology and Human Genomics, Academy of Sciences of the Republic of Uzbekistan, Tashkent, Republic of Uzbekistan
2Tashkent Medical Academy, Tashkent, Republic of Uzbekistan
3National Pediatric Medical Center, Tashkent, Republic of Uzbekistan
4Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Republic of Uzbekistan

Objective: To identify clinical and immunological changes in patients with long-term non-healing wounds (LTNHW) on the background of diabetes mellitus (DM).

Methods: Thirty-four patients with LTNHW on the background of DM were enrolled in the study as the main group, with twenty healthy individuals comprising the control group. The clinical picture of LTNHW was evaluated based on the local necrobiotic process. The immunological status was assessed based on parameters of cellular and humoral immunity

Results: Against the background of a local inflammatory process, tissue necrosis was discovered in more than one half of the wounds. At the same time, the local exudative process directly depended on the type of necrobiotic changes in the wound. In patients with LTNHW, compared to the baseline, a significant increase in the absolute counts of CD3+, CD4+, CD8+, CD20+, CD23+, and CD38+ cells was found in the course of treatment. With respect to the dynamics of CD25+, CD95+, and CD16+ cells, multidirectional changes of relative and absolute counts were identified against a background of elevated IL-17A and IL-10 cytokine levels (p<0.001).

Conclusion: In patients with LTNHW on a background of DM, despite the variable forms of the necrobiotic process, several changes are consistently observed, indicating imbalances in T- and B-lymphocyte ratios, which may reflect immunological strain. An unfavorable prognosis for the course of LTNHW in patients with DM is associated with a significant increase in IL-17A and IL-10 cytokine levels.

Keywords: Long-term non-healing wounds, diabetes mellitus, cellular immunity, humoral immunity, wound necrobiotic process..

Download file:

References
  1. Shanmugam VK, Angra D, Rahimi H, McNish S. Vasculitic and autoimmune wounds. J Vasc Surg Venous Lymphat Disord. 2017;5(2):280-92. https://doi. org/10.1016/j.jvsv.2016.09.006
  2. Larouche J, Sheoran S, Maruyama K, Martino MM. Immune regulation of skin wound healing: Mechanisms and novel therapeutic targets. Adv Wound Care (New Rochelle). 2018;7(7):209-31. https://doi.org/10.1089/wound.2017.0761
  3. Strang H, Kaul A, Parikh U, Masri L, Saravanan S, Li H, et al. Role of cytokines and chemokines in wound healing. In: Wound Healing, Tissue Repair, and Regeneration in Diabetes; Bagchi D, Das A, Roy S, Eds. Elsevier: Amsterdam, The Netherlands; 2020; pp. 197-235.
  4. Piipponen M, Li D, Landén NX. The immune functions of keratinocytes in skin wound healing. Int J Mol Sci. 2020;21(22):8790. https://doi.org/10.3390/ ijms21228790
  5. Li D, Peng H, Qu L, Sommar P, Wang A, Chu T, et al. MiR-19a/b and miR20a promote wound healing by regulating the inflammatory response of keratinocytes. J Invest Dermatol. 2021;141(3):659-71. https://doi.org/10.1016/j. jid.2020.06.037
  6. Yuan L, Sun Y, Xu M, Zeng F, Xiong X. MiR-203 acts as an inhibitor for epithelial-mesenchymal transition process in diabetic foot ulcers via targeting interleukin-8. Neuroimmunomodulation. 2019;26(5):239-49. https://doi. org/10.1159/000503087
  7. Wu J, Li X, Li D, Ren X, Li Y, Herter EK, et al. MicroRNA-34 family enhances wound inflammation by targeting LGR4. J Invest Dermatol. 2020;140(2):465-76.e11. https://doi.org/10.1016/j.jid.2019.07.694
  8. Huang YZ, Gou M, Da LC, Zhang WQ, Xie HQ. Mesenchymal stem cells for chronic wound healing: Current status of preclinical and clinical studies. Tissue Eng Part B Rev. 2020;26(6):555-70. https://doi.org/10.1089/ten.TEB.2019.0351
  9. Petrov RV, Dozmorov IM, Zadorozhnyĭ SI, Orlov EV. Vzaimodeĭstvie lim-fotsitov cheloveka s krovetvornymi stvolovymi kletkami myshi [Interaction of human lymphocytes with mouse hematopoietic stem cells]. Dokl Akad Nauk SSSR. 1987;296(1):246-8
  10. Böyum A. Separation of leukocytes from blood and bone marrow. Introduction. Scand J Clin Lab Invest Suppl. 1968;97:7
  11. Garib FY, Rizopulu AP. T-Regulatory cells as part of strategy of immune evasion by pathogens. Biochemistry (Mosc). 2015;80(8):957-71. https://doi.org/10.1134/ S0006297915080015
  12. Tottoli EM, Dorati R, Genta I, Chiesa E, Pisani S, Conti B. Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics. 2020;12(8):735. https://doi.org/10.3390/pharmaceutics12080735
  13. Theocharidis G, Baltzis D, Roustit M, Tellechea A, Dangwal S, Khetani RS, et al. Integrated skin transcriptomics and serum multiplex assays reveal novel mechanisms of wound healing in diabetic foot ulcers. Diabetes. 2020;69(10):2157-69. https://doi.org/10.2337/db20-0188
  14. Sawaya AP, Stone RC, Brooks SR, Pastar I, Jozic I, Hasneen K, et al. Deregulated immune cell recruitment orchestrated by FOXM1 impairs human diabetic wound healing. Nat Commun. 2020;11(1):4678. https://doi.org/10.1038/s41467-020- 18276-0
  15. Saito K, Iwata Y, Fukushima H, Watanabe S, Tanaka Y, Hasegawa Y, et al. IL-36 receptor antagonist deficiency resulted in delayed wound healing due to excessive recruitment of immune cells. Sci Rep. 2020;10(1):14772. https://doi. org/10.1038/s41598-020-71256-8
  16. Barros JF, Waclawiak I, Pecli C, Borges PA, Georgii JL, Ramos-Junior ES, et al. Role of chemokine receptor CCR4 and regulatory T-cells in wound healing of diabetic mice. J Invest Dermatol. 2019;139(5):1161-70. https://doi.org/10.1016/j. jid.2018.10.039
  17. Seraphim PM, Leal EC, Moura J, Gonçalves P, Gonçalves JP, Carvalho E. Lack of lymphocytes impairs macrophage polarization and angiogenesis in diabetic wound healing. Life Sci. 2020;254:117813. https://doi.org/10.1016/j. lfs.2020.117813
  18. Nguyen TT, Ding D, Wolter WR, Pérez RL, Champion MM, Mahasenan KV, et al. Validation of matrix metalloproteinase-9 (MMP-9) as a novel target for treatment of diabetic foot ulcers in humans and discovery of a potent and selective small-molecule MMP-9 inhibitor that accelerates healing. J Med Chem. 2018;61(19):8825-37. https://doi.org/10.1021/acs.jmedchem.8b01005
  19. Lang J, Yang C, Liu L, Li L, Wu L, Liu Y, et al. High glucose activates ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic foot ulcers. Exp Cell Res. 2021;403(1):112550. https://doi.org/10.1016/j.yexcr.2021.112550

Authors' information:

Aripova Tamara Uktamovna,
Academician of the Academy of Sciences of the Republic of Uzbekistan, Doctor of Medical Sciences, Full Professor, Director, Institute of Immunology and Human Genomics, Academy of Sciences of the Republic of Uzbekistan
Researcher ID: CDE-3916-2022
Scopus ID: 57223045214
ORCID ID: 0000-0001-9783-9600
E-mail: t.aripova@immuno.uz

Okhunov Alisher Oripovich,
Doctor of Medical Sciences, Full Professor, Head of the Department of General and Pediatric Surgery, Tashkent Medical Academy
Researcher ID: HKO-2361-2023
Scopus ID: 6508358215
ORCID ID: 0000-0003-3622-6805
SPIN: 2943-1604
Author ID: 989103
E-mail: general-surgery@mail.ru

Umarov Bakhtiyorzhon Yatgarovich,
PhD, Director, National Pediatric Medical Center
Researcher ID: LUY-9203-2024
Scopus ID: 57254991600
ORCID ID: 0000-0001-9173-2028
E-mail: bakhtiyorumarov@mail.ru

Khamdamov Bakhtiyar Zarifovich,
Doctor of Medical Sciences, Full Professor, Head of the Department of Faculty and Hospital Surgery, Bukhara State Medical Institute named after Abu Ali ibn Sino
Scopus ID: 57221665311
ORCID ID: 0000-0003-3569-6688
Author ID: 57221665311
E-mail: dr.hamdamov@mail.ru

Information about support in the form of grants, equipment, medications

The research was carried out in accordance with the research plan of Tashkent Medical Academy (state registration number – 142001/20018). The authors did not receive financial support from manufacturers of medicines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Okhunov Alisher Oripovich
Doctor of Medical Sciences, Full Professor, Head of the Department of General and Pediatric Surgery, Tashkent Medical Academy

100109, Republic of Uzbekistan, Tashkent, Farobi str., 2

Tel.: +998 (909) 474568

E-mail: general-surgery@mail.ru


This work is licensed under a Creative Commons Attribution 4.0 International License.

Materials on the topic:
  1. OPTIMIZED PERIOPERATIVE MANAGEMENT (FAST-TRACK, ERAS) TO ENHANCE POSTOPERATIVE RECOVERY IN PANCREATICODUODENECTOMY
  2. ACUTE CALCULOUS CHOLECYSTITIS COMPLICATED BY NONSPECIFIC REACTIVE HEPATITIS AND JAUNDICE: CURRENT TRENDS IN DIAGNOSIS AND TREATMENT
  3. CONTEMPORARY DIAGNOSIS OF HEPATIC HYDATID ECHINOCOCCOSIS
  4. COMPLEX CLINICAL SCENARIOS IN ABDOMINAL SURGERY: A CASE REPORT
  5. ACUTE ADHESIVE SMALL BOWEL OBSTRUCTION: ROLE OF DOPPLER ULTRASONOGRAPHY IN PATIENT MANAGEMENT
  6. APPLICATION OF EXTRACORPOREAL DETOXIFICATION METHODS IN THE COMPLEX TREATMENT OF PATIENTS WITH INFECTED PANCREATIC NECROSIS
  7. RETROSPECTIVE ANALYSIS OF THE SURGICAL TREATMENT OUTCOMES FOR DIFFUSE PERITONITIS
  8. PREDICTION OF PERSISTENT PERITONITIS IN THE POSTOPERATIVE PERIOD
  9. REASONS FOR UNSATISFACTORY TREATMENT RESULTS OF ACUTE PURULENT DESTRUCTIVE LUNG DISEASES IN PATIENTS WITH SARS-COV-2 INFECTION
  10. CLEAR CELL RENAL CANCER IN RENAL ALLOGRAFT: CASE STUDY AND LITERATURE REVIEW

◄ Back to the list