1.γ-Oryzanol Ameliorates Endothelial Replicative Senescence via Downregulation of SGLT2 Expression to Attenuate NADPH-Driven Oxidative Stress
Saugat SHIWAKOTI ; Kushal SHARMA ; Dal-Seong GONG ; Ju-Young KO ; In-Young LEE ; Hyun-Jung KIM ; Min-Ho OAK
Biomolecules & Therapeutics 2026;34(2):401-412
Replicative senescence in endothelial cells is characterized by an irreversible cell cycle arrest and impaired endothelial function, contributing to vascular aging and cardiovascular disease. Natural compounds are being actively studied for their potential to delay cellular senescence and protect vascular health. Among them, rice bran has demonstrated several vascular benefits that are mainly attributed to gamma-oryzanol (γ-Orz), a major bioactive component in rice bran. However, its role in regulating endothelial replicative senescence and the underlying molecular mechanisms remain unclear. This study aimed to explore the protective effects of rice bran extract (RBE) and γ-Orz on replicative senescence in porcine coronary artery endothelial cells (PCAECs). Replicative senescence was modeled in PCAECs by serial passaging from P1 to P3 with varying concentrations of RBE and γ-Orz.Senescence was evaluated by measuring senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, oxidative stress, and the expression of cell cycle regulatory proteins. RBE and γ-Orz significantly reduced SA-β-gal activity, improved proliferation, and decreased oxidative stress in P3 cells, along with downregulation of senescence-related proteins p53, p21, and p16. Additionally, γ-Orz suppressed sodium-glucose co-transporter 2 expression, reduced NADPH oxidase overexpression, and restored eNOS levels. These findings indicate that RBE and γ-Orz delay endothelial senescence by alleviating oxidative stress, highlighting their potential to reduce cardiovascular disease risk associated with endothelial senescence.
2.Tonsil-derived mesenchymal stem cells protect the kidney from gentamicin-induced acute kidney injury by incorporation into damaged renal tubules and amelioration of oxidative and endoplasmic reticulum stresses
Mina YU ; Dal-Ah KIM ; Eun-Sun RYU ; Sung Min JUNG ; Sung-Chul JUNG ; Inho JO ; Han Su KIM ; Duk-Hee KANG
Kidney Research and Clinical Practice 2025;44(6):899-915
Background:
Stem cell-based therapy is one of the tools for acute kidney injury (AKI) treatment. Tonsil tissue is a promising alternative source for the high-yield isolation of mesenchymal stem cells (MSCs). This study was undertaken to investigate the effects of tonsil-derived MSCs (T-MSCs) in animal model of AKI induced by gentamicin (GM).
Methods:
Twenty Sprague-Dawley rats were divided into four groups: Control, GM (70 mg/kg/day, intraperitoneal injection for 10 days), GM + T-MSCs (1 × 107 cells, intravenous injection at 1 day after the last vehicle/GM), and T-MSCs. Renal function, apoptosis, and markers of endoplasmic reticulum stress were measured on day 16 after the first vehicle/GM. Oxidative stress was assessed by measuring urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the expression of glutathione peroxidase (GPx) and catalase. Effects of T-MSCs on GM-induced apoptosis and oxidative stress in NRK cells were also evaluated using a co-culture technique of NRK cells and T-MSC.
Results:
In the GM + T-MSCs group, blood urea nitrogen, creatinine, and tubular damage score were lower compared to the GM group. T-MSCs injection decreased apoptotic cells and the expression of Bax, cytochrome c, and cleaved caspase and increased Bcl-2. T-MSC injection decreased urinary 8-OHdG and increased expression of GPx and catalase in the kidneys. Anti-human nuclei and PKH26 staining demonstrated the localization of T-MSCs in the tubules of renal cortex. In-vitro study revealed that T-MSCs or T-MSC-conditioned media ameliorated GM-induced nicotinamide adenine dinucleotide phosphate oxidase-1 expression, hydrogen peroxide generation, and apoptosis of NRK cells.
Conclusion
Our study demonstrated that T-MSCs ameliorated GM-induced AKI by directly incorporating into the damaged renal tubules and exerting antiapoptotic and antioxidative effects.
3.Glioblastoma Immunotherapy Adjuvants for Glial Cell Polarization Regulation
Jun Seo PARK ; Dong Geon LEE ; Dal-Hee MIN ; Sung Joong LEE
Experimental Neurobiology 2025;34(6):235-247
Glioblastoma (GBM) remains fatal despite maximal surgical resection, temozolomide chemotherapy, and radiotherapy. Within the GBM microenvironment, tumor-educated microglia and astrocytes adopt immunoregulatory-like STAT3-high and ARG1/TGF-β-high phenotypes, respectively, which shield GBM cells from adaptive immune attack. In this review, we examine emerging adjuvant strategies designed to molecularly reprogram glial cells toward pro-inflammatory C3-high and IFN/NF-κB-high states, amplifying antitumor immunity. First, we summarize key aspects of GBM pathobiology and identify why conventional treatments fail to achieve durable control. Next, we dissect the signaling networks that govern glial phase states, including NF-κB, STAT3, IRF3, NLRP3, and cGAS-STING axes. We then provide a mechanism-centric analysis of pattern-recognition receptor (PRR) agonists, inflammasome modulators, and cyclic-dinucleotide STING agonists, integrating quantitative preclinical data with early clinical trial results. For each adjuvant, we distinguish between direct astrocytic engagement and indirect cytokine-mediated reprogramming.Modulation of glial phase states holds considerable promise for enhancing personalized vaccine efficacy and for converting immunologically “cold” GBM into a T cell-inflamed tumor. Consequently, targeting glial cell phase modulation is a highly attractive strategy for GBM immunotherapy, with the potential to maximize therapeutic benefit. Despite advances in chemo-, radio-, and checkpoint-blockade therapies, the immunosuppressive tumor microenvironment (TME) of GBM and its failure to establish memory immunity limit their impact. Tumor-polarized astrocytes and microglia form a barrier to effective T cell-mediated attack. Emerging evidence shows that redirecting glia toward pro-inflammatory phenotypes can recondition the TME, creating a more permissive landscape for immunotherapy. This review highlights glial phase reprogramming as a promising immunoadjuvant approach, emphasizing molecular circuits, synthetic modulators, and translational prospects.
4.2023 Korean Thyroid Association Management Guidelines for Patients with Subclinical Hypothyroidism
Hyun Kyung CHUNG ; Eu Jeong KU ; Won Sang YOO ; Yea Eun KANG ; Kyeong Jin KIM ; Bo Hyun KIM ; Tae-Yong KIM ; Young Joo PARK ; Chang Ho AHN ; Jee Hee YOON ; Eun Kyung LEE ; Jong Min LEE ; Eui Dal JUNG ; Jae Hoon CHUNG ; Yun Jae CHUNG ; Won Bae KIM ; Ka Hee YI ; Ho-Cheol KANG ; Do Joon PARK
International Journal of Thyroidology 2023;16(1):32-50
Subclinical hypothyroidism (SCH), characterized by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine levels, usually presents without symptoms, and is often discovered incidentally during routine blood test. The Task Force of the Korean Thyroid Association Committee of Clinical Practice Guidelines has established a guideline to evaluate and manage SCH; the guideline emphasizes the implementation of diagnostic criteria based on the TSH reference range for Koreans and focuses on the proven health benefits of levothyroxine (LT4) treatment. Based on the Korea National Health and Nutrition Examination Survey (2013-2015), serum TSH level of 6.8 mIU/L is considered the reference value for SCH. SCH can be categorized as mild (TSH 6.8-10.0 mIU/L) or severe (TSH >10.0 mIU/L), and patients are classified as adults (age <70 years) or elderly patients (age ≥70years) depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, along with the thyroid peroxidase antibody test, preferably 2-3 months after the initial evaluation. Usually, LT4 treatment is not recommended for mild SCH in adults; however, treatment is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and can be considered for coexisting dyslipidemia. LT4 treatment is not recommended for mild or even severe SCH in elderly patients, in general. Patients with SCH who receive LT4 treatment, the LT4 dosage should be personalized, and serum TSH levels should be monitored to ensure optimal LT4 dosage (dosage that is neither excessive nor insufficient). Patients with SCH who do not receive LT4 treatment require periodic follow-up at appropriate testing intervals determined by disease severity. The guideline also provides several educational points applicable in clinical settings.
5.2023 Korean Thyroid Association Management Guidelines for Patients with Subclinical Hypothyroidism
Hyun Kyung CHUNG ; Eu Jeong KU ; Won Sang YOO ; Yea Eun KANG ; Kyeong Jin KIM ; Bo Hyun KIM ; Tae-Yong KIM ; Young Joo PARK ; Chang Ho AHN ; Jee Hee YOON ; Eun Kyung LEE ; Jong Min LEE ; Eui Dal JUNG ; Jae Hoon CHUNG ; Yun Jae CHUNG ; Won Bae KIM ; Ka Hee YI ; Ho-Cheol KANG ; Do Joon PARK
International Journal of Thyroidology 2023;16(2):214-215
6.A Position Statement of the Utilization and Support Status of Continuous Glucose Monitoring in Korea
Won Jun KIM ; Jae Hyun KIM ; Hye Jin YOO ; Jang Won SON ; Ah Reum KHANG ; Su Kyoung KWON ; Ji Hye KIM ; Tae Ho KIM ; Ohk Hyun RYU ; Kyeong Hye PARK ; Sun Ok SONG ; Kang-Woo LEE ; Woo Je LEE ; Jung Hwa JUNG ; Ho-Chan CHO ; Min Jeong GU ; Jeongrim LEE ; Dal Lae JU ; Yeon Hee LEE ; Eun Kyung KIM ; Young Sil EOM ; Sung Hoon YU ; Chong Hwa KIM ;
Journal of Korean Diabetes 2021;22(4):225-237
The accuracy and convenience of continuous glucose monitoring (CGM), which efficiently evaluates glycemic variability and hypoglycemia, are improving. There are two types of CGM: professional CGM and personal CGM. Personal CGM is subdivided into real-time CGM (rt-CGM) and intermittently scanned CGM (isCGM). CGM is being emphasized in both domestic and foreign diabetes management guidelines. Regardless of age or type of diabetes, CGM is useful for diabetic patients undergoing multiple insulin injection therapy or using an insulin pump. rt-CGM is recommended for all adults with type 1 diabetes (T1D), and can also be used in type 2 diabetes (T2D) treatments using multiple insulin injections. In some cases, short-term or intermittent use of CGM may be helpful for patients with T2D who use insulin therapy other than multiple insulin injections and/or oral hypoglycemic agents. CGM can help to achieve A1C targets in diabetes patients during pregnancy. CGM is a safe and cost-effective alternative to self-monitoring blood glucose in T1D and some T2D patients. CGM used in diabetes management works optimally with proper education, training, and follow up. To achieve the activation of CGM and its associated benefits, it is necessary to secure sufficient repetitive training and time for data analysis, management, and education. Various supports such as compensation, insurance coverage expansion, and reimbursement are required to increase the effectiveness of CGM while considering the scale of benefit recipients, policy priorities, and financial requirements.
7.Surgical Treatment of Primary Pulmonary Myopericytoma.
Jeong Min MUN ; Jong In KIM ; Taek Yong KO ; Sung Dal PARK
The Korean Journal of Thoracic and Cardiovascular Surgery 2018;51(3):220-222
Myopericytoma is a benign tumor that occurs in soft tissues. Myopericytoma in the lungs is very rare. We report the case of a 63-year-old woman presenting with cavitary masses in the left lung and multiple tiny nodules in both lungs. She underwent surgery, and a histological examination revealed primary pulmonary myopericytoma.
Female
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Humans
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Lung
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Middle Aged
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Multiple Pulmonary Nodules
8.The Clinical Implications of Death Domain-Associated Protein (DAXX) Expression.
Taek Yong KO ; Jong In KIM ; Eok Sung PARK ; Jeong Min MUN ; Sung Dal PARK
The Korean Journal of Thoracic and Cardiovascular Surgery 2018;51(3):187-194
BACKGROUND: Death domain-associated protein (DAXX), originally identified as a pro-apoptotic protein, is now understood to be either a pro-apoptotic or an anti-apoptotic factor with a chromatin remodeler, depending on the cell type and context. This study evaluated DAXX expression and its clinical implications in squamous cell carcinoma of the esophagus. METHODS: Paraffin-embedded tissues from 60 cases of esophageal squamous carcinoma were analyzed immunohistochemically. An immune reaction with more than 10% of tumor cells was interpreted as positive. Positive reactions were sorted into 2 groups: reactions in 11%–50% of tumor cells and reactions in more than 51% of tumor cells, and the correlations between expression and survival and clinical prognosticators were analyzed. RESULTS: Forty-three of the 60 cases (71.7%) showed strong nuclear DAXX expression, among which 19 cases showed a positive reaction (31.7%) in 11%–50% of tumor cells, and 24 cases (40.0%) showed a positive reaction in more than 51% of tumor cells. A negative reaction was found in 17 cases (28.3%). These patterns of immunostaining were significantly associated with the N stage (p=0.005) and American Joint Committee on Cancer stage (p=0.001), but overall survival showed no significant difference. There were no correlations of DAXX expression with age, gender, or T stage. However, in stage IIB (p=0.046) and stage IV (p=0.014) disease, DAXX expression was significantly correlated with survival. CONCLUSION: This investigation found upregulation of DAXX in esophageal cancer, with a 71.7% expression rate. DAXX immunostaining could be used in clinical practice to predict aggressive tumors with lymph node metastasis in advanced-stage disease, especially in stages IIB and IV.
Carcinoma, Squamous Cell
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Chromatin
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Esophageal Neoplasms
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Esophagus
;
Joints
;
Lymph Nodes
;
Neoplasm Metastasis
;
Up-Regulation
9.Principles for evaluating the clinical implementation of novel digital healthcare devices
Seong Ho PARK ; Kyung Hyun DO ; Joon Il CHOI ; Jung Suk SIM ; Dal Mo YANG ; Hong EO ; Hyunsik WOO ; Jeong Min LEE ; Seung Eun JUNG ; Joo Hyeong OH
Journal of the Korean Medical Association 2018;61(12):765-775
With growing interest in novel digital healthcare devices, such as artificial intelligence (AI) software for medical diagnosis and prediction, and their potential impacts on healthcare, discussions have taken place regarding the regulatory approval, coverage, and clinical implementation of these devices. Despite their potential, ‘digital exceptionalism’ (i.e., skipping the rigorous clinical validation of such digital tools) is creating significant concerns for patients and healthcare stakeholders. This white paper presents the positions of the Korean Society of Radiology, a leader in medical imaging and digital medicine, on the clinical validation, regulatory approval, coverage decisions, and clinical implementation of novel digital healthcare devices, especially AI software for medical diagnosis and prediction, and explains the scientific principles underlying those positions. Mere regulatory approval by the Food and Drug Administration of Korea, the United States, or other countries should be distinguished from coverage decisions and widespread clinical implementation, as regulatory approval only indicates that a digital tool is allowed for use in patients, not that the device is beneficial or recommended for patient care. Coverage or widespread clinical adoption of AI software tools should require a thorough clinical validation of safety, high accuracy proven by robust external validation, documented benefits for patient outcomes, and cost-effectiveness. The Korean Society of Radiology puts patients first when considering novel digital healthcare tools, and as an impartial professional organization that follows scientific principles and evidence, strives to provide correct information to the public, make reasonable policy suggestions, and build collaborative partnerships with industry and government for the good of our patients.
Artificial Intelligence
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Delivery of Health Care
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Device Approval
;
Diagnosis
;
Diagnostic Imaging
;
Humans
;
Insurance Coverage
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Korea
;
Patient Care
;
Societies
;
Software Validation
;
United States
;
United States Food and Drug Administration
10.Principles for evaluating the clinical implementation of novel digital healthcare devices
Seong Ho PARK ; Kyung Hyun DO ; Joon Il CHOI ; Jung Suk SIM ; Dal Mo YANG ; Hong EO ; Hyunsik WOO ; Jeong Min LEE ; Seung Eun JUNG ; Joo Hyeong OH
Journal of the Korean Medical Association 2018;61(12):765-775
With growing interest in novel digital healthcare devices, such as artificial intelligence (AI) software for medical diagnosis and prediction, and their potential impacts on healthcare, discussions have taken place regarding the regulatory approval, coverage, and clinical implementation of these devices. Despite their potential, ‘digital exceptionalism’ (i.e., skipping the rigorous clinical validation of such digital tools) is creating significant concerns for patients and healthcare stakeholders. This white paper presents the positions of the Korean Society of Radiology, a leader in medical imaging and digital medicine, on the clinical validation, regulatory approval, coverage decisions, and clinical implementation of novel digital healthcare devices, especially AI software for medical diagnosis and prediction, and explains the scientific principles underlying those positions. Mere regulatory approval by the Food and Drug Administration of Korea, the United States, or other countries should be distinguished from coverage decisions and widespread clinical implementation, as regulatory approval only indicates that a digital tool is allowed for use in patients, not that the device is beneficial or recommended for patient care. Coverage or widespread clinical adoption of AI software tools should require a thorough clinical validation of safety, high accuracy proven by robust external validation, documented benefits for patient outcomes, and cost-effectiveness. The Korean Society of Radiology puts patients first when considering novel digital healthcare tools, and as an impartial professional organization that follows scientific principles and evidence, strives to provide correct information to the public, make reasonable policy suggestions, and build collaborative partnerships with industry and government for the good of our patients.

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