Seunghwan Lee

Background and Objectives: Liver regeneration following partial hepatectomy (PHx) is essential for restoring hepatic function. Polydeoxyribonucleotide (PDRN), an adenosine A_2A receptor (A_2AR) agonist, has demonstrated regenerative and proangiogenic properties in various tissues. However, its therapeutic potential for promoting liver regeneration after PHx has not been fully elucidated. The primary objective was to evaluate the effect of PDRN on liver regeneration after PHx, and the secondary objective was to examine associated changes in proliferation-related proteins and A_2AR/cAMP, HGF/c-Met, and VEGF/VEGFR2 signaling. Materials and Methods: A rat model of 70% PHx was established, and PDRN (8 mg/kg) was administered intraperitoneally once daily for 5 consecutive days with or without the A_2AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX; 8 mg/kg). Liver regeneration was evaluated using biochemical, histological, and molecular analyses. Results: PDRN enhanced liver regeneration following PHx, as demonstrated by reduced serum liver enzyme levels, enhanced recovery of liver mass, and improved histological architecture. PDRN also increased the expression of the proliferation-associated proteins proliferating cell nuclear antigen (PCNA) and cyclin D1. These effects were accompanied by increased A_2AR expression and cyclic adenosine monophosphate (cAMP) levels, elevated hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels, and enhanced phosphorylation of c-Met and VEGFR2. Co-administration of DMPX attenuated the regenerative and molecular effects of PDRN, suggesting a potential involvement of A_2AR-related signaling. Conclusions: Collectively, these findings suggest that PDRN may facilitate liver regeneration following PHx in association with increased expression of proliferation-associated proteins and changes in HGF/c-Met and VEGF/VEGFR2 signaling, supporting its potential as a therapeutic strategy following hepatic resection.

Background/Objectives: Polydeoxyribonucleotide (PDRN) has anti-inflammatory and tissue-protective properties associated with activation of the adenosine A_2A receptor (A_2AR). Although hepatoprotective actions of PDRN have previously been described, its potential association with high-mobility group box 1 (HMGB1)-related inflammatory responses and hepatic macrophage accumulation during acute liver injury (ALI) is not fully understood. This study examined whether PDRN affects HMGB1- and monocyte chemoattractant protein-1 (MCP-1)-associated responses together with hepatic macrophage accumulation in ALI. Methods: ALI was induced in ICR mice by carbon tetrachloride (CCl₄) administration. PDRN was administered either alone or together with the selective A_2AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). Serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were quantified. Histological alterations were evaluated using hematoxylin and eosin staining. Hepatic macrophage accumulation was assessed by F4/80 immunofluorescence staining. Enzyme-linked immunosorbent assays were used to quantify HMGB1, MCP-1, interleukin-10 (IL-10), cyclic adenosine monophosphate (cAMP), and A_2AR. Results: PDRN significantly reduced serum markers of liver injury and attenuated histopathological damage following CCl₄ administration. PDRN treatment also decreased F4/80-positive macrophage accumulation in the hepatic tissue. In addition, PDRN reduced HMGB1 and MCP-1 levels in both the serum and liver tissues while significantly increasing IL-10, cAMP, and A_2AR levels. Conclusions: PDRN attenuated CCl₄-induced ALI and was associated with reduced HMGB1 and MCP-1 levels, decreased hepatic macrophage accumulation, and increased A_2AR/cAMP signaling. These findings suggest that modulation of macrophage-associated inflammatory responses may contribute to the hepatoprotective effects of PDRN.

Hong Seok Han, Seung Hwan Lee, Geun Hyeok Yang, Sun-Hyung Joo, Hyun Cheol Kim. Ann Hepatobiliary Pancreat Surg 2026;30:352-9. https://doi.org/10.14701/ahbps.26-125

Background/Objectives: Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by abdominal pain, diarrhea, and bleeding. Polydeoxyribonucleotide (PDRN), an adenosine A_2A receptor (A_2AR) agonist, exhibits anti-inflammatory properties. In the present study, we evaluated the therapeutic effects of PDRN in a dextran sodium sulfate (DSS)-induced murine model of UC. Methods: UC was induced by administering 2% DSS in drinking water for 7 days. One day after DSS administration, mice received intraperitoneal injections of PDRN (8 mg/kg) for 7 days. To investigate the involvement of A_2AR, the selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 8 mg/kg) was co-administered with PDRN. Results: DSS administration induced colonic tissue damage and increased disease activity index (DAI) and histological scores. DSS also elevated pro-inflammatory cytokines while reducing anti-inflammatory cytokine levels. PDRN treatment reduced histological damage, restored body weight, colon weight, and colon length, and decreased DAI scores. Furthermore, PDRN treatment inhibited nuclear factor kappa B (NF-κB) activation through suppression of NF-κB inhibitor-α phosphorylation and was associated with activation of the cAMP/PKA/CREB signaling pathway. PDRN treatment attenuated inflammation and was associated with increased expression of vascular endothelial growth factor (VEGF) in colonic tissues. Given the context-dependent role of VEGF in inflammatory bowel disease, this increase is interpreted as contributing to mucosal repair rather than exacerbating inflammation. Co-administration of DMPX abolished these effects, suggesting the involvement of A_2AR-dependent signaling pathways. Conclusions: PDRN attenuated colonic inflammation and improved disease outcomes in DSS-induced UC, potentially through modulation of the PKA/CREB/NF-κB signaling pathway and VEGF-mediated tissue repair mechanisms.

Kim H, et al. Ann Surg Treat Res. 2023 May;104(5):288-295. https://doi.org/10.4174/astr.2023.104.5.288

Shon S, et al. Ann Surg Treat Res. 2023 Jan;104(1):27-33. https://doi.org/10.4174/astr.2023.104.1.27

Ki Duk Kim, Hyangkyoung Kim, Sungsin Cho, Seung Hwan Lee, and Jin Hyun Joh. Vasc Specialist Int 2022;38:. https://doi.org/10.5758/vsi.220046

Namkee Oh, Min Jung Kim, Kyo Won Lee, Hyun Cho, Sook Young Woo, Jinsoo Rhu, Seunghwan Lee, Jong Man Kim, Gyu-Seong Choi, Jae Berm Park, Jae-Won Joh. Korean J Transplant 2022;36:173-9. https://doi.org/10.4285/kjt.22.0018

Background: Protocol biopsy in renal allograft helps to early detect subclinical rejection (SCR) in patients who have no abnormal clinical and laboratory findings. Still, there are rare reports about the techniques and outcomes of two-week protocol biopsy. The aim of this study was to assess two-week protocol biopsy regarding the technical feasibility, procedure safety, and clinical outcomes. Methods: A total of 894 protocol biopsies were performed in adult recipients between 2012 and 2019. Two-week and one-year protocol biopsies were guided with ultrasound in 842 and 399 patients by one of four radiologists with wide range of biopsy experience, respectively. These protocol biopsies were compared in terms of feasibility and safety. Standard references were clinico-laboratory findings and biopsy examinations. Results: The median period of two-week and one-year protocol biopsies were 12 days (10–20 days) and 383 days (302–420 days), respectively. All protocol biopsies were technically successful and there was no difference between radiologists regarding technical success and complications (p = 0.453). Major complication (Clavien–Dindo grading II–IV) rates of two-week and one-year protocol biopsies were 0.3% (3/842) and 0.2% (1/399), respectively (p = 1.000). However, univariate analysis demonstrated that platelet count < 100 K/mL and blood urea nitrogen ≥ 40 mg/dL were associated with major complications in two-week protocol biopsy. The SCRs of these protocol biopsies were 15.4% (130/842) and 33.6% (134/399), respectively (p < 0.001). Conclusion: Two-week protocol biopsy is technically feasible and safe. It contributes to early detecting a substantial number of SCRs. Prior to the biopsy, platelet count and blood urea nitrogen should be carefully checked to predict major complications.

Seunghwan Lee. Journal of Minimally Invasive Surgery 2021;24:182-3. https://doi.org/10.7602/jmis.2021.24.4.182