1.β-Catenin and AMPK/AKT/FOXO Signaling Mediate Doxorubicin-Induced Senescence and Lipid Accumulation in C2C12 Myoblasts
Chawon YUN ; Sou Hyun KIM ; Doyoung KWON ; RanJu WOO ; Ki Wung CHUNG ; Jaewon LEE ; Yun-Hee LEE ; Young-Suk JUNG
Biomolecules & Therapeutics 2026;34(1):136-145
Skeletal muscle atrophy is a major complication associated with aging, chronic disease, and chemotherapy. Doxorubicin (Dox), a widely used anticancer agent, accelerates muscle wasting; however, the underlying cellular mechanisms remain poorly understood. In this study, we examined the effects of Dox on myogenic differentiation, senescence, and lipid metabolism using C2C12 myoblasts. Dox exposure impaired myotube formation without causing overt cytotoxicity. Mechanistically, Dox disrupted myogenic differentiation by inhibiting protein kinase B/mammalian target of rapamycin (AKT/mTOR) signaling, thereby de-repressing forkhead box O1/3 (FOXO1/3) and upregulating the muscle-specific ubiquitin ligases muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1), which promote proteolysis. Dox also decreased glycogen synthase kinase 3β (GSK3β) phosphorylation while paradoxically increasing total and phosphorylated β-catenin, indicating dysregulated Wnt/β-catenin signaling. These alterations were accompanied by a senescence-like phenotype, characterized by elevated senescence-associated β-galactosidase (SA-β-gal) activity, increased phosphorylated histone variant γH2AX, and activation of the p53–p21 axis. Notably, cellular senescence coincided with excessive lipid accumulation in myotubes. Dox reduced phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) while enhancing expression of key lipogenic regulators, thereby creating a metabolic environment favoring lipid storage. Collectively, these findings demonstrate that Dox not only suppresses myogenic differentiation but also induces premature senescence and metabolic reprogramming toward lipid accumulation. Targeting these pathways through AMPK activation, FOXO inhibition, or senolytic interventions may offer therapeutic strategies to preserve skeletal muscle integrity in patients undergoing chemotherapy.
2.Long-Term Evaluation of Cannabidiol in Pediatric Drug-Resistant Epilepsy: A Real-Time Single-Center Retrospective Study
Jong Ho CHA ; Hyeryung KIM ; Young Ho KIM ; Seungbok LEE ; Soo Yeon KIM ; Byung Chan LIM ; Jong-Hee CHAE ; Ki Joong KIM ; Woo Joong KIM
Annals of Child Neurology 2026;34(1):66-74
Purpose:
Cannabidiol (CBD) is a promising treatment option for pediatric drug-resistant epilepsy (DRE). The aim of this study was to assess the tolerability and safety of CBD in a single-center retrospective cohort based on real-world clinical experience.
Methods:
This study included 71 pediatric patients (median age, 8.9 years; interquartile range [IQR], 6.2 to 14.0) with Lennox–Gastaut syndrome who received purified CBD (Epidiolex, GW Pharmaceuticals) between March 2019 and July 2024. All patients had previously failed treatment with more than five anti-seizure medications (ASMs). Responder rate (≥50% seizure frequency reduction), retention rate, adverse effects (AEs), and predictors of favorable treatment response were analyzed over a median follow-up of 21.3 months (IQR, 2.8 to 38.5).
Results:
The initial responder rate during the first 3 months was 45.1%, which increased to 70.8% at 18 months and 63.0% at 24 months. The retention rate at 24 months was 52.4% (33/71). Seven patients (9.9%) achieved seizure freedom beyond 24 months of CBD therapy, and five of these patients were able to reduce their concomitant ASM burden. AEs were observed in 39.4% (28/71) of patients, with the most frequent being somnolence (20 cases) and increased seizure frequency (six cases); 92.9% of AEs occurred within the first 3 months of treatment. No serious AEs requiring treatment discontinuation were identified.
Conclusion
In this real-world study, CBD demonstrated potential as an adjunctive therapy with manageable AEs. These findings highlight that CBD can reduce seizure frequency while maintaining tolerability in pediatric patients with DRE.
3.The Korean Rectal Cancer Multidisciplinary Committee Clinical Practice Guidelines for Rectal Cancer version 2.0
Hyo Seon RYU ; Hyun Jung KIM ; Dong Hyun KANG ; Yoo-Kang KWAK ; Han Deok KWAK ; Yoon-Hye KWON ; Dalyon KIM ; Baek-Hui KIM ; Jae Hyun KIM ; Ji Hun KIM ; Jin Won KIM ; Tae Hyung KIM ; Hae Young KIM ; Soo Min NAM ; Gyoung Tae NOH ; Jun Woo BONG ; Nak Song SUNG ; Seon Hui SHIN ; Kil-Yong LEE ; Sung Chul LEE ; Sea-Won LEE ; Jung Won LEE ; Jong Min LEE ; Myung Hoon IHN ; Joo Han LIM ; Woong Bae JI ; Dae Hee PYO ; Young Ki HONG ; Jung-Myun KWAK ;
Annals of Coloproctology 2026;42(1):4-33
Rectal cancer, which accounts for approximately 40% of colorectal cancers, remains a major clinical concern. Recent advances in diagnostic imaging, surgical techniques, radiotherapy, and systemic treatment have steadily improved rectal cancer outcomes. Considering this, the Korean Rectal Cancer Multidisciplinary (KRCM) Committee has aimed to provide clinicians and policymakers with up-to-date, evidence-based clinical practice guidelines to support optimal decision-making, reflecting current evidence, the Korean healthcare context, and patient values and preferences. The Clinical Practice Guidelines for Rectal Cancer version 2.0 were developed through multidisciplinary collaboration with related academic societies, building upon and updating the KRCM Clinical Practice Guidelines version 1.0 (titled “Multidisciplinary guidelines for the management of rectal cancer”). These consensus guidelines of the KRCM were established based on a comprehensive literature review, evidence synthesis, with recommendation development guided by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and consideration of applicability in real-world clinical practice under the national health insurance system. Each recommendation has been presented with its strength and level of evidence.
4.Calorie Restriction Modulates Gene Expression of Il19 and Il24 during Renal Aging
Sang Gyun NOH ; Hyun Woo KIM ; Seungwoo KIM ; Mi Kyung KIM ; Byung Pal YU ; Ki Wung CHUNG ; Hae Young CHUNG
Annals of Geriatric Medicine and Research 2026;30(1):28-40
Background:
Renal function declines with age as the kidneys become more vulnerable to inflammation and cellular senescence. This study examined gene expression changes linked to renal aging and assessed whether short-term calorie restriction (CR), a known anti-aging intervention, could reverse these alterations.
Methods:
Using RNA-seq data, we applied bioinformatics, systems biology, and molecular biology approaches to identify differentially expressed genes during aging and under CR. Gene Ontology and pathway analyses revealed that both aging and CR altered the expression of key senescence-associated secretory phenotype (SASP) genes, including cytokines and chemokines (Il1b, Ccl3, Ccl5, Il19, and Il24) and growth factors (Timp1 and Mmp12).
Results:
Renal aging is also associated with an increased expression of cell cycle arrest markers (p15INK4B (Cdkn2b), p16INK4A (Cdkn2a), and p21 (Cdkn1a)), which are suppressed by CR, suggesting a link to cellular senescence. Quantitative analysis of renal tissue samples confirmed the age-associated upregulation of these genes at the transcriptional level, and CR effectively attenuated these changes. Among these genes, we focused on the members of the interleukin 20 (IL-20) family, particularly Il19 and Il24. Furthermore, experimental induction of cellular senescence using H2O2 resulted in elevated Il19 and Il24 expression alongside other senescence markers. These findings suggest that aging and short-term CR regulate the IL-20 family expression, potentially influencing cellular senescence.
Conclusion
Our study suggests that Il19 and Il24 are associated with age-related renal decline and may represent hypothesis-generating candidates, highlighting potential molecular targets for future mechanistic and therapeutic investigations.
5.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part II. Follow-up Surveillance after Initial Treatment 2026
Eun Kyung LEE ; Seung Heon KANG ; Bon Seok KOO ; Mijin KIM ; Min Joo KIM ; Bo Hyun KIM ; Ji Won KIM ; Dong Gyu NA ; Sohyun PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Young-Ik SON ; Young Shin SONG ; Dong Yeob SHIN ; Jong-Hyuk AHN ; Hwa Young AHN ; So Won OH ; Ho-Ryun WON ; Won Sang YOO ; Min Kyoung LEE ; Sang-Woo LEE ; Jeongmin LEE ; Ji Ye LEE ; Dong-Jun LIM ; Ki-Wook CHUNG ; Ari CHONG ; Jin Hyang JUNG ; Sun Wook CHO ; Yoon Young CHO ; Chae Moon HONG ; Young Joo PARK ;
International Journal of Thyroidology 2026;19(1):1-40
In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.
6.Poor Prognosis of Pneumococcal Co-Infection in Hospitalized Patients with COVID-19: A Propensity Score-Matched Analysis
Soyoon HWANG ; Eunkyung NAM ; Shin-Woo KIM ; Hyun-Ha CHANG ; Yoonjung KIM ; Sohyun BAE ; Nan Young LEE ; Yu Kyung KIM ; Ji Sun KIM ; Han Wook PARK ; Joon Gyu BAE ; Juhwan JEONG ; Ki Tae KWON
Infection and Chemotherapy 2025;57(1):172-178
The impact of Streptococcus pneumoniae coinfection on coronavirus disease 2019 (COVID-19) prognosis remains uncertain. We conducted a retrospective analysis of patients hospitalized with COVID-19 who underwent a pneumococcal urinary antigen (PUA) test to assess its clinical utility. Results showed that PUA-positive patients required more oxygen support, high-flow nasal cannula, and dexamethasone compared to PUA-negative patients.Furthermore, the significantly higher incidence of a National Early Warning Score ≥5 in the PUA-positive group (P<0.001) suggests that a positive PUA test is associated with a severe disease course. However, no significant difference in mortality was observed between the two groups, and antibiotics were used in almost all patients (96.2%). While the PUA test may help guide antibiotic use in COVID-19 patients, its interpretation should be approached with caution.
7.A Study on the Healthcare Workforce and Care for Acute Stroke: Results From the Survey of Hospitals Included in the National Acute Stroke Quality Assessment Program
Jong Young LEE ; Jun Kyeong KO ; Hak Cheol KO ; Hae-Won KOO ; Hyon-Jo KWON ; Dae-Won KIM ; Kangmin KIM ; Myeong Jin KIM ; Hoon KIM ; Keun Young PARK ; Kuhyun YANG ; Jae Sang OH ; Won Ki YOON ; Dong Hoon LEE ; Ho Jun YI ; Heui Seung LEE ; Jong-Kook RHIM ; Dong-Kyu JANG ; Youngjin JUNG ; Sang Woo HA ; Seung Hun SHEEN
Journal of Korean Medical Science 2025;40(16):e44-
Background:
With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey.
Methods:
For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke.
Results:
In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high.
Conclusion
Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.
8.Sex Differences in Procedural Characteristics and Clinical Outcomes Among Patients Undergoing Bifurcation PCI
Hyun Jin AHN ; Francesco BRUNO ; Jeehoon KANG ; Doyeon HWANG ; Han-Mo YANG ; Jung-Kyu HAN ; Leonardo De LUCA ; Ovidio de FILIPPO ; Alessio MATTESINI ; Kyung Woo PARK ; Alessandra TRUFFA ; Wojciech WANHA ; Young Bin SONG ; Sebastiano GILI ; Woo Jung CHUN ; Gerard HELFT ; Seung-Ho HUR ; Bernardo CORTESE ; Seung Hwan HAN ; Javier ESCANED ; Alaide CHIEFFO ; Ki Hong CHOI ; Guglielmo GALLONE ; Joon-Hyung DOH ; Gaetano De FERRARI ; Soon-Jun HONG ; Giorgio QUADRI ; Chang-Wook NAM ; Hyeon-Cheol GWON ; Hyo-Soo KIM ; Fabrizio D’ASCENZO ; Bon-Kwon KOO
Korean Circulation Journal 2025;55(1):5-16
Background and Objectives:
The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men.
Methods:
COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization.
Results:
Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups.
Conclusions
In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.
9.Outcomes of Deferring Percutaneous Coronary Intervention Without Physiologic Assessment for Intermediate Coronary Lesions
Jihoon KIM ; Seong-Hoon LIM ; Joo-Yong HAHN ; Jin-Ok JEONG ; Yong Hwan PARK ; Woo Jung CHUN ; Ju Hyeon OH ; Dae Kyoung CHO ; Yu Jeong CHOI ; Eul-Soon IM ; Kyung-Heon WON ; Sung Yun LEE ; Sang-Wook KIM ; Ki Hong CHOI ; Joo Myung LEE ; Taek Kyu PARK ; Jeong Hoon YANG ; Young Bin SONG ; Seung-Hyuk CHOI ; Hyeon-Cheol GWON
Korean Circulation Journal 2025;55(3):185-195
Background and Objectives:
Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment.
Methods:
A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years.
Results:
The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization.
Conclusions
For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.
10.Development of a Standardized Suicide Prevention Program for Gatekeeper Intervention in Korea (Suicide CARE Version 2.0) to Prevent Adolescent Suicide: Version for Teachers
Hyeon-Ah LEE ; Yeon Jung LEE ; Kyong Ah KIM ; Myungjae BAIK ; Jong-Woo PAIK ; Jinmi SEOL ; Sang Min LEE ; Eun-Jin LEE ; Haewoo LEE ; Meerae LIM ; Jin Yong JUN ; Seon Wan KI ; Hong Jin JEON ; Sun Jung KWON ; Hwa-Young LEE
Psychiatry Investigation 2025;22(1):117-117

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