1.KEAP1-NRF2 Pathway as a Novel Therapeutic Target for EGFR-Mutant Non-small Cell Lung Cancer
Jae-Sun CHOI ; Hye-Min KANG ; Kiyong NA ; Jiwon KIM ; Tae-Woo KIM ; Junyang JUNG ; Heejin LIM ; Hyewon SEO ; Seung Hyeun LEE
Tuberculosis and Respiratory Diseases 2025;88(1):138-149
Background:
Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer.
Methods:
We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition.
Results:
Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways.
Conclusion
We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.
2.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.
3.Non-Inferiority Analysis of Electrocardiography Analysis Application vs. Point-of-Care Ultrasound for Screening Left Ventricular Dysfunction
Jin Hee KIM ; Jae Yun JUNG ; Joonghee KIM ; Youngjin CHO ; Eunkyoung LEE ; Dahyeon SON
Yonsei Medical Journal 2025;66(3):172-178
Purpose:
Point-of-care ultrasound (POCUS) is widely used for heart function evaluation in emergency departments (EDs), but requires specific equipment and skilled operators. This study evaluates the diagnostic accuracy of a mobile application for estimating left ventricular (LV) systolic dysfunction [left ventricular ejection fraction (LVEF) <40%] using electrocardiography (ECG) and tests its non-inferiority to POCUS.
Materials and Methods:
Patients (aged ≥20 years) were included if they had both a POCUS-based EF evaluation and an ECG within 24 hours of their ED visit between January and May 2022, along with formal echocardiography within 2 weeks before or after the visit. A mobile app (ECG Buddy, EB) estimated LVEF (EF from EB) and the risk of LV dysfunction (LV-Dysfunction score) from ECG waveforms, which were compared to NT-proBNP levels and POCUS-evaluated LVEF (EF from POCUS). A non-inferiority margin was set at an area under the curve (AUC) difference of 0.05.
Results:
Of the 181 patients included, 37 (20.4%) exhibited LV dysfunction. The AUCs for screening LV dysfunction using POCUS and NT-proBNP were 0.885 and 0.822, respectively. EF from EB and LV-Dysfunction score outperformed NT-proBNP, with AUCs of 0.893 and 0.884, respectively (p=0.017 and p=0.030, respectively). EF from EB was non-inferior to EF from POCUS, while LV-Dysfunction score narrowly missed the mark. A subgroup analysis of sinus-origin rhythm ECGs supported the non-inferiority of both EF from EB and LV-Dysfunction score to EF from POCUS.
Conclusion
A smartphone application that analyzes ECG image can screen for LV dysfunction with a level of accuracy comparable to that of POCUS.
4.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.
5.Prevalence and factors influencing postpartum depression and its culture-specific cutoffs for women in Asia: a scoping review
Bora MOON ; Hyun Kyoung KIM ; Ju-Hee NHO ; Hyunkyung CHOI ; ChaeWeon CHUNG ; Sook Jung KANG ; Ju Hee KIM ; Ju-Young LEE ; Sihyun PARK ; Gisoo SHIN ; Ju-Eun SONG ; Min Hee LEE ; Sue KIM
The Ewha Medical Journal 2025;48(1):e15-
The prevalence of postpartum depression (PPD) in Asia is reported to range from 13.53% to 22.31%. However, there remains a gap in the identification of PPD, particularly regarding cultural cutoff points. Therefore, the purpose of this scoping review was to determine the prevalence and associated factors of PPD in Eastern, South-eastern, Western, and Southern Asian countries and analyze the cutoff points of the Edinburgh Postnatal Depression Scale (EPDS) used across these countries. Following Arksey and O'Malley’s five-step scoping review framework, the population was defined as mothers, the concept as the EPDS, and the context as the Asian region. A literature search was conducted using PubMed, Embase, CINAHL, PsycINFO, and Web of Science. The data analysis focused on demographic characteristics, EPDS cutoffs and features, PPD prevalence, and its associated factors. Nineteen studies were selected. Most countries used translated versions of the EPDS with demonstrated reliability and validity. The cutoff scores varied, with most using scores of 10 or higher. The prevalence of PPD ranged from 5.1% to 78.7%. Key associated factors for PPD included cultural factors such as relationships with in-laws and preferences for the newborn’s sex. To improve the accuracy of PPD screening in Asia, the EPDS should be used consistently, and appropriate cutoff criteria must be established. In addition, prevention strategies and programs that reflect the cultural characteristics and social context of Asia need to be developed for the early detection and prevention of PPD.
6.Medical Nutrition Therapy as a Hospital-Based Lifestyle Modification in the Korean Diabetes Prevention Study
Ji Hye CHOI ; Jung-Hwa LEE ; Suk CHON
Journal of Korean Diabetes 2025;26(1):39-47
The prevalence of prediabetes has steadily increased in Korea, driven by rising obesity rates and lifestyle changes. A structured lifestyle modification program has been shown to significantly reduce the prevalence of diabetes among adults with prediabetes, with this effect sustained over time. Lifestyle modifications including medical nutrition, exercise, and behavioral psychological therapy are effective for preventing and managing diabetes, with medical nutrition therapy playing a crucial role. This study reviews the latest academic guidelines and medical nutrition therapy for diabetes prevention and to introduce the KDPS-hLSM (Korean Diabetes Prevention Study hospital-based lifestyle modification).
8.A Case Study of Gestational Diabetes Education Using a Smart Platform
Journal of Korean Diabetes 2025;26(1):32-38
Gestational diabetes mellitus (GDM) affects 2~10% of pregnant women worldwide, with an increasing prevalence in South Korea that reached 18.2% in 2021. Unmanaged GDM can lead to serious complications for both mother and fetus. Effective management requires blood glucose monitoring and lifestyle changes, but many women lack sufficient knowledge about the condition. This study explores the use of smart platforms, like continuous glucose monitoring devices and mobile apps, to improve GDM education. Devices such as Dexcom G7 and FreeStyle Libre 2 enable real-time blood glucose monitoring, while apps like Health2Sync help patients share data with healthcare providers. Although these technologies offer major benefits, challenges remain in patient engagement, data accuracy, and accessibility. In conclusion, while smart platforms can enhance GDM management, they must be combined with ongoing professional support to improve health outcomes.
9.Experts’ Perceptions Regarding Testing for Helicobacter pylori Infection During Upper Gastrointestinal Endoscopy and Subsequent Eradication Therapy
Ilsoo KIM ; Sang Pyo LEE ; Jeong Wook KIM ; Heung Up KIM ; Tae Ho KIM ; Seung Young KIM ; Yu Jin KIM ; Hee Seok MOON ; Jung In LEE ; Woon Geon SHIN ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2025;25(1):81-86
Helicobacter pylori causes gastric cancer and peptic ulcers, and eradication therapy can reduce the incidence of cancer in high-risk groups. In Korea, discrepancies between the reimbursement criteria and clinical guidelines create clinical challenges. This study investigated the perceptions and practices of experts regarding H. pylori testing during upper gastrointestinal endoscopy and any subsequent eradication therapy. An anonymous 8-question survey was conducted among 51 experts attending the 2024 Korean College of Helicobacter and Upper Gastrointestinal Research Summer Workshop. Only 2% of the experts tested all patients. Testing was performed in 54% of patients with a family history of gastric cancer, 32% of those with atrophic gastritis, 42% of those with dyspeptic symptoms, and 62% of those with iron-deficiency anemia. Among patients with suspected infections (based on endoscopic findings) and eligible for selective reimbursement, 82% underwent H. pylori testing. Age did not influence testing decisions for 60% of the experts, and 57% considered factors other than age when deciding on eradication therapy. The practices of the experts varied depending on the patient’s clinical condition and economic burden. Aligning clinical guidelines with the reimbursement criteria is necessary to reduce confusion and ensure appropriate patient care.
10.Reduced-intensity chemotherapy with tyrosine kinase inhibitor followed by allogeneic transplantation is effective in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
Jung Min LEE ; Do Young KIM ; Hee Jeong CHO ; Joon Ho MOON ; Sang Kyun SOHN ; Ho Jin SHIN ; Young Rok DO ; Mi Hwa HEO ; Min Kyoung KIM ; Young Seob PARK ; Dong Won BAEK
The Korean Journal of Internal Medicine 2025;40(1):124-134
Background/Aims:
To determine the effectiveness of tyrosine kinase inhibitor (TKI) plus reduced-intensity therapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), this retrospective study compared treatment outcomes and induction mortality according to backbone regimen intensity.
Methods:
The data of 132 patients diagnosed with Ph-positive ALL were retrospectively collected from five centers. Patients received imatinib plus intensive chemotherapy (modified VPD, KALLA1407, or hyper-CVAD) or reduced-intensity chemotherapy (EWALL) for curative purposes. This study analyzed 117 patients, of which 35,22,46, and 14 received modified VPD, KALLA1407, hyper-CVAD, and EWALL, respectively. All patients used imatinib as a TKI.
Results:
The median age of the patients who received reduced-intensity chemotherapy was 64.4 years, while that of the patients with intensive regimens was 47.5 years. There was no induction death in the reduced-intensity group, while nine patients died in the intensive therapy group. Major molecular response achievement tended to be higher in the intensive chemotherapy group than in the reduced-intensity group. More patients in the intensive chemotherapy group received allogeneic stem cell transplantation (allo-SCT). There was no statistically significant difference in long-term survival between the two groups in terms of relapse-free survival and overall survival rates.
Conclusions
When imatinib plus reduced-intensity therapy was used as a frontline treatment, there was no inferiority in obtaining complete remission compared to imatinib plus intensive chemotherapy or significant difference in long-term survival. Since imatinib plus reduced-intensity therapy has limitations in obtaining a deep molecular response, proceeding to allo-SCT should be considered.

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