1.Potential of histone deacetylase 6 inhibitors in alleviating chemotherapy-induced peripheral neuropathy
Su Jung PARK ; Soung-Min LEE ; Seong Mook KANG ; Hyun-Mo YANG ; Su-Kil SEO ; Ju-Hee LEE
The Korean Journal of Pain 2025;38(2):152-162
Background:
Histone deacetylase 6 (HDAC6), belonging to class IIb of histone deacetylases, regulates theacetylation of the cytoplasmic protein α-tubulin. The overexpression of HDAC6 is linked to the development oftumors, and inhibiting HDAC6 is known to trigger apoptosis in multiple myeloma cells. In addition to its application in cancer treatment, bortezomib, a proteasome inhibitor, is widely used in managing multiple myeloma and has shown effectiveness in patients with both newly diagnosed and relapsed disease. However, the treatment regimen may be delayed or discontinued due to the risk of peripheral neuropathy, a significant non-hematologic side effect.
Methods:
Animal models of peripheral neuropathy induced by various anti-cancer drugs were established, confirming the potential of HDAC6 inhibitors as a treatment for this condition. Six- to eight-week-old male Sprague Dawley rats were utilized to create these models. Mechanical allodynia and electron microscopy served as indicators of peripheral neuropathy. The HDAC6 inhibitor CKD-011 was administered at doses of 5, 10, 20, and 40 mg/kg.
Results:
In an animal model of bortezomib-induced peripheral neuropathy, CKD-011, an HDAC6 inhibitor, effectively ameliorated peripheral neuropathy. Similarly, CKD-011 administration demonstrated recovery from peripheral neuropathy in models induced with oxaliplatin, paclitaxel, and cisplatin.
Conclusions
These findings suggest that HDAC6 inhibitors have the potential to mitigate peripheral neuropathy induced by chemotherapeutic agents.
2.Understanding of Patients with Severe COVID-19 Using Lung Ultrasound
Seo-Hee YANG ; Eun Ju PARK ; Jung-Hyun KIM ; Jin Woo SONG ; Young-Jae CHO
Tuberculosis and Respiratory Diseases 2025;88(2):380-387
Background:
Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge.
Methods:
We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores.
Results:
We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05).
Conclusion
This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.
3.Vitamin D Attenuates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obesity Murine Model
Sook In CHUNG ; Lin LIANG ; Heejae HAN ; Kyung Hee PARK ; Jae-Hyun LEE ; Jung-Won PARK
Yonsei Medical Journal 2025;66(2):75-86
Purpose:
Obesity and metabolic syndrome are acknowledged as key factors contributing to the development of non-alcoholic fatty liver disease (NAFLD). Vitamin D (VitD) is a multifaceted secosteroid hormone known for its anti-fibrotic and anti-inflammatory properties, with its deficiency often linked to obesity. Our study aimed to investigate whether VitD supplementation could mitigate the liver pathology associated with NAFLD.
Materials and Methods:
The NAFLD model was developed by subjecting male C57BL/6 mice to a high-fat diet (HFD) for 14 weeks.These mice were supplemented with VitD through intraperitoneal injection at a dosage of 7 μg/kg, administered three times per week for 7 weeks.
Results:
HFD resulted in VitD deficiency, insulin resistance, and increased liver weight. It elevated serum levels of liver aminotransferases and triglyceride, ultimately leading to steatohepatitis with fibrosis. This model exhibited increased levels of transforming growth factor (TGF)-β1, pro-inflammatory cytokines, HNF4α transcription factors, reactive oxygen species (ROS), renin-angiotensin system activity, and epithelial-mesenchymal transitions (EMT) within the liver. Supplementation with VitD resulted in the recovery of liver weight, improvement in histologic features associated with steatohepatitis, and reduction in alanine aminotransferases and triglyceride levels induced by the HFD. Additionally, it mitigated the HFD-induced over-expressions of TGF-β1 and fibrosis-related genes, along with pro-inflammatory cytokines and ROS. Notably, no adverse effect was found due to VitD supplementation in this model.
Conclusion
VitD ameliorates steatohepatitis within obesity-induced NAFLD through its multifaceted pathways. VitD supplementation emerges as a potentially safe, cost-effective, and direct treatment approach for NAFLD patients dealing with obesity or metabolic dysfunction.
4.Differences in Treatment Outcomes Depending on the Adjuvant Treatment Modality in Craniopharyngioma
Byung Min LEE ; Jaeho CHO ; Dong-Seok KIM ; Jong Hee CHANG ; Seok-Gu KANG ; Eui-Hyun KIM ; Ju Hyung MOON ; Sung Soo AHN ; Yae Won PARK ; Chang-Ok SUH ; Hong In YOON
Yonsei Medical Journal 2025;66(3):141-150
Purpose:
Adjuvant treatment for craniopharyngioma after surgery is controversial. Adjuvant external beam radiation therapy (EBRT) can increase the risk of long-term sequelae. Stereotactic radiosurgery (SRS) is used to reduce treatment-related toxicity.In this study, we compared the treatment outcomes and toxicities of adjuvant therapies for craniopharyngioma.
Materials and Methods:
We analyzed patients who underwent craniopharyngioma tumor removal between 2000 and 2017. Of the 153 patients, 27 and 20 received adjuvant fractionated EBRT and SRS, respectively. We compared the local control (LC), progression-free survival (PFS), and overall survival between groups that received adjuvant fractionated EBRT, SRS, and surveillance.
Results:
The median follow-up period was 77.7 months. For SRS and surveillance, the 10-year LC was 57.2% and 57.4%, respectively. No local progression was observed after adjuvant fractionated EBRT. One patient in the adjuvant fractionated EBRT group died owing to glioma 94 months after receiving radiotherapy (10-year PFS: 80%). The 10-year PFS was 43.6% and 50.7% in the SRS and surveillance groups, respectively. The treatment outcomes significantly differed according to adjuvant treatment in nongross total resection (GTR) patients. Additional treatment-related toxicity was comparable in the adjuvant fractionated EBRT and other groups.
Conclusion
Adjuvant fractionated EBRT could be effective in controlling local failure, especially in patients with non-GTR, while maintaining acceptable treatment-related toxicity.
5.Feasibility of a Machine Learning Classifier for Predicting Post-Induction Hypotension in Non-Cardiac Surgery
Insun PARK ; Jae Hyon PARK ; Young Hyun KOO ; Chang-Hoon KOO ; Bon-Wook KOO ; Jin-Hee KIM ; Ah-Young OH
Yonsei Medical Journal 2025;66(3):160-171
Purpose:
To develop a machine learning (ML) classifier for predicting post-induction hypotension (PIH) in non-cardiac surgeries.
Materials and Methods:
Preoperative data and early vital signs were obtained from 3669 cases in the VitalDB database, an opensource registry. PIH was defined as sustained mean arterial pressure (MAP) <65 mm Hg within 20 minutes since induction or from induction to incision. Six different ML algorithms were used to create binary classifiers to predict PIH. The primary outcome was the area under the receiver operating characteristic curve (AUROC) of ML classifiers.
Results:
A total of 2321 (63.3%) cases exhibited PIH. Among ML classifiers, the random forest regressor and extremely gradient boosting regressor showed the highest AUROC, both recording a value of 0.772. Excluding these models, the light gradient boosting machine regressor showed the second highest AUROC [0.769; 95% confidence interval (CI), 0.767–0.771], followed by the gradient boosting regressor (0.768; 95% CI, 0.763–0.772), AdaBoost regressor (0.752; 95% CI, 0.743–0.761), and automatic relevance determination regression (0.685; 95% CI, 0.669–0.701). The top three important features were mean diastolic blood pressure (DBP), minimum MAP, and minimum DBP from anesthetic induction to tracheal intubation, and these features were lower in cases with PIH (all p<0.001).
Conclusion
ML classifiers exhibited moderate performance in predicting PIH, and have the potential for real-time prediction.
6.Mixture of Mastic Gum and Peppermint Extracts Promotes Hair Growth and Health in Vitro and in C57BL/6 Mice
Seoyoon HAM ; Young In LEE ; Yujin JANG ; Sang Gu LEE ; Jangmi SUK ; Inhee JUNG ; Jae Hyun PARK ; Ju Hee LEE
Yonsei Medical Journal 2025;66(5):310-320
Purpose:
Hair disorders, which are often attributed to conditions associated with a shortened anagen growth phase, oxidative stress, and hormonal dysregulation, especially during aging, have profound psychological implications. Currently, only minoxidil has been approved as a topical hair growth solution; thus, alternative therapies for treating hair loss and promoting hair health are urgently needed. Herein, we aimed to develop and assess a novel method to promote hair growth and health using mastic (Pistacia lentiscus) gum and peppermint (Mentha piperita L.) extracts.
Materials and Methods:
After determining the optimal ratio of mastic gum and peppermint extracts, we performed in vitro and in vivo experiments to verify the efficacy of the 7:3 mastic gum-peppermint mixture (MP73; FHH-MG) for enhancing hair growth and health.
Results:
Mastic gum significantly promoted cell proliferation and demonstrated synergistic benefits when combined with peppermint extract. In vitro, FHH-MG increased human dermal follicle papilla cell proliferation and demonstrated anti-inflammatory and antioxidant effects. In vivo, treatment with FHH-MG dose-dependently enhanced hair growth and gloss and increased the expression of vascular endothelial growth factor, epidermal growth factor, β-catenin, and insulin-like growth factor-1 in C57BL/6 mice compared to the negative control.
Conclusion
The novel mixture exhibited hair growth-promoting effects in C57BL/6 mice; thus, FHH-MG may serve as a botanical alternative for hair growth and health promotion.
7.Laparoscopic and robotic surgery for colorectal cancer in Korea: a nationwide health insurance database analysis from 2019 to 2023
Eun Ji PARK ; Hyun Gu LEE ; Youn Young PARK ; Sun Jin PARK ; Kil Yeon LEE ; Suk-Hwan LEE
Journal of Minimally Invasive Surgery 2025;28(1):25-35
Purpose:
This study examined nationwide data regarding laparoscopic and robotic surgery for colorectal cancer (CRC) in Korea.
Methods:
Nationwide data concerning patients who underwent surgery for CRC from 2019 to 2023 were obtained from the Health Insurance Review and Assessment Service database.
Results:
From 2019 to 2023, a total of 109,573 patients with CRC underwent surgical resection in Korea. Among these, open, laparoscopic, and robotic surgery comprised 17.2%, 71.5%, and 11.3%, respectively. Open surgery decreased from 18.3% in 2019 to 15.2% in 2023, whereas robotic surgery increased from 10.3% in 2019 to 12.7% in 2023. Regarding rectal cancer, the rate of robotic surgery increased from 23.0% in 2019 to 28.2% in 2023, and the rate of minimally invasive surgery (MIS) increased from 86.9% in 2019 to 89.2% in 2023.Patients with National Health Insurance had significantly shorter lengths of hospital stay after surgery than those with medical aid for all surgical methods (p < 0.0001). With respect to hospital size, 74,282 CRC surgeries (67.8%) were performed in tertiary general hospitals and 33,050 (30.2%) in general hospitals. By the region, 47,140 cases (43.0%) were performed in Seoul, 19,961 (18.2%) in Gyeonggi, and 7,417 (6.8%) in Daegu. Ostomy was created in 16,222 CRC surgeries (14.8%).
Conclusion
The rate of MIS adoption for CRC in Korea has increased, reaching 84.7% in 2023. The rate of laparoscopic surgery exceeded 70% and has plateaued. In contrast, the rate of robotic surgery adoption has steadily increased, particularly for rectal cancer, where it surpassed 28% in 2023.
8.Erratum to "Investigating the Immune-Stimulating Potential of β-Glucan from Aureobasidium pullulans in Cancer Immunotherapy" Biomol Ther 32(5), 556-567 (2024)
Jae-Hyeon JEONG ; Dae-Joon KIM ; Seong-Jin HONG ; Jae-Hee AHN ; Dong-Ju LEE ; Ah-Ra JANG ; Sungyun KIM ; Hyun-Jong CHO ; Jae-Young LEE ; Jong-Hwan PARK ; Young-Min KIM ; Hyun-Jeong KO
Biomolecules & Therapeutics 2025;33(1):233-233
9.Erratum to "Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress" Biomol Ther 32(3), 349-360 (2024)
Hyun HWANGBO ; Cheol PARK ; EunJin BANG ; Hyuk Soon KIM ; Sung-Jin BAE ; Eunjeong KIM ; Youngmi JUNG ; Sun-Hee LEEM ; Young Rok SEO ; Su Hyun HONG ; Gi-Young KIM ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):555-555
10.Paeoniflorin Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage by Activating Nrf2-Mediated HO-1 Signaling
Cheol PARK ; Hee-Jae CHA ; Su Hyun HONG ; Jeong Sook NOH ; Sang Hoon HONG ; Gi Young KIM ; Jung-Hyun SHIM ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):518-528
Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

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