1.Carnosine and Retinol Synergistically Inhibit UVB-Induced PGE2Synthesis in Human Keratinocytes through the Up-Regulation of Hyaluronan Synthase 2
In Guk PARK ; Sun Hee JIN ; Seungchan AN ; Min Won KI ; Won Seok PARK ; Hyoung-June KIM ; Yongjoo NA ; Minsoo NOH
Biomolecules & Therapeutics 2024;32(5):635-639
Skin aging results from complex interactions of intrinsic and extrinsic factors, leading to structural and biochemical changes such as wrinkles and dryness. Ultraviolet (UV) irradiation leads to the degradation of hyaluronic acid (HA) in the skin, and the fragmented HA contributes to inflammation. This study revealed that the synergistic combination of carnosine and retinol (ROL) increases HA production in normal human epidermal keratinocytes (NHEKs) by upregulating hyaluronan synthase 2 (HAS2) gene transcription. Simultaneously, the combined treatment of carnosine and ROL significantly attenuates UVB-induced prostaglandin E2 (PGE2) synthesis in NHEKs. A significant correlation exists between the increase of HA synthesis and the inhibition of PGE2 production. This study suggests that combined treatment of carnosine and ROL can improve skin aging phenotypes associated with UVB irradiation.
2.Differential effects of premorbid functional dependency on mortality in patients with anterior and posterior circulation stroke
Min-Surk KYE ; Do Yeon KIM ; Dong-Wan KANG ; Baik Kyun KIM ; Jung Hyun PARK ; Hyung Seok GUK ; Nakhoon KIM ; Sang-Won CHOI ; Jun Yup KIM ; Jihoon KANG ; Beom Joon KIM ; Moon-Ku HAN ; Hee-Joon BAE
Journal of Neurocritical Care 2024;17(1):16-23
Background:
This study investigated the impact of premorbid functional dependency on post-stroke mortality in patients with anterior circulation stroke (ACS) and posterior circulation stroke (PCS).
Methods:
This study enrolled 9,698 patients who experienced ischemic stroke between January 2011 and December 2022. The patients were classified into the ACS and PCS groups. Premorbid functional dependency was defined as modified Rankin Scale of ≥3. The risks of premorbid functional dependency and mortality at 3 months and 1-year post-stroke were assessed. A subgroup analysis was further performed to evaluate the risk of premorbid functional dependency in patients who underwent intravenous thrombolysis and endovascular treatment (EVT).
Results:
Among 6,358 patients with ACS and 3,340 with PCS, those with premorbid dependency were older, predominantly female, and had a higher proportion of vascular risk factors and stroke severity. Premorbid functional dependency was associated with increased mortality at both 3 months and 1 year in the PCS (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.00–3.13; P=0.04 and OR, 2.87; 95% CI, 1.86–4.38; P<0.001, respectively), but not in the ACS (OR, 1.08; 95% CI, 0.77–1.51; P=0.639 and OR, 1.22; 95% CI, 0.93–1.59; P=0.140, respectively) group. Among patients who underwent EVT, premorbid functional dependency increased the risk of mortality at 1 year in the ACS group (OR, 1.80; 95% CI, 1.04–3.08; P=0.034), but was not associated with the risk in the PCS group (OR 2.56; 95% CI 0.64–10.15; P=0.176).
Conclusion
Premorbid functional dependency increases the risk of mortality in patients with PCS.
3.Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator
Hyejin KO ; Seungchan AN ; Hongjun JANG ; Sungjin AHN ; In Guk PARK ; Seok Young HWANG ; Junpyo GONG ; Soyeon OH ; Soo Yeon KWAK ; Won Jun CHOI ; Hyoungsu KIM ; Minsoo NOH
Biomolecules & Therapeutics 2023;31(3):312-318
The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesisinducing activity by macakurzin C derivatives (2–7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.
4.Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09)
Jieun LEE ; Keun Seok LEE ; Sung Hoon SIM ; Heejung CHAE ; Joohyuk SOHN ; Gun Min KIM ; Kyung-Hee LEE ; Su Hwan KANG ; Kyung Hae JUNG ; Jae-ho JEONG ; Jae Ho BYUN ; Su-Jin KOH ; Kyoung Eun LEE ; Seungtaek LIM ; Hee Jun KIM ; Hye Sung WON ; Hyung Soon PARK ; Guk Jin LEE ; Soojung HONG ; Sun Kyung BAEK ; Soon Il LEE ; Moon Young CHOI ; In Sook WOO
Cancer Research and Treatment 2023;55(1):123-135
Purpose:
The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.
Materials and Methods:
We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.
Results:
The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).
Conclusion
Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.
5.Novel Asian-Specific Visceral Adiposity Indices Are Associated with Chronic Kidney Disease in Korean Adults
Jonghwa JIN ; Hyein WOO ; Youngeun JANG ; Won-Ki LEE ; Jung-Guk KIM ; In-Kyu LEE ; Keun-Gyu PARK ; Yeon-Kyung CHOI
Diabetes & Metabolism Journal 2023;47(3):426-436
Background:
The Chinese visceral adiposity index (CVAI) and new visceral adiposity index (NVAI) are novel indices of visceral adiposity used to predict metabolic and cardiovascular diseases in Asian populations. However, the relationships of CVAI and NVAI with chronic kidney disease (CKD) have not been investigated. We aimed to characterize the relationships of CVAI and NVAI with the prevalence of CKD in Korean adults.
Methods:
A total of 14,068 participants in the 7th Korea National Health and Nutrition Examination Survey (6,182 men and 7,886 women) were included. Receiver operating characteristic (ROC) analyses were employed to compare the associations between indices of adiposity and CKD, and a logistic regression model was used to characterize the relationships of CVAI and NVAI with CKD prevalence.
Results:
The areas under the ROC curves for CVAI and NVAI were significantly larger than for the other indices, including the visceral adiposity index and lipid accumulation product, in both men and women (all P<0.001). In addition, high CVAI or NVAI was significantly associated with a high CKD prevalence in both men (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31 to 3.48 in CVAI and OR, 6.47; 95% CI, 2.91 to 14.38 in NVAI, P<0.05) and women (OR, 4.87; 95% CI, 1.85 to 12.79 in CVAI and OR, 3.03; 95% CI, 1.35 to 6.82 in NVAI, P<0.05); this association remained significant after adjustment for multiple confounding factors in men and women.
Conclusion
CVAI and NVAI are positively associated with CKD prevalence in a Korean population. CVAI and NVAI may be useful for the identification of CKD in Asian populations, including in Korea.
6.Effect of Xenogeneic Substances on the Glycan Profiles and Electrophysiological Properties of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Yong Guk KIM ; Jun Ho YUN ; Ji Won PARK ; Dabin SEONG ; Su-hae LEE ; Ki Dae PARK ; Hyang-Ae LEE ; Misun PARK
International Journal of Stem Cells 2023;16(3):281-292
Background and Objectives:
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold greatpromise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy.
Methods:
and Results: We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances(xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (ACTC1, TNNT2, and RYR2) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring-mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM.
Conclusions
To the best of our knowledge, this is the first study to show that the electrophysiological function andglycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.
7.A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation
Guk Jin LEE ; Hyunho KIM ; Sung Shim CHO ; Hyung Soon PARK ; Ho Jung AN ; In Sook WOO ; Jae Ho BYUN ; Ji Hyung HONG ; Yoon Ho KO ; Der Sheng SUN ; Hye Sung WON ; Jong Youl JIN ; Ji Chan PARK ; In-Ho KIM ; Sang Young ROH ; Byoung Yong SHIM
Journal of Gastric Cancer 2023;23(2):315-327
Purpose:
Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy.
Materials and Methods:
Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level.
Results:
Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020).
Conclusions
After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.
8.Effects of Telephone Hotline Counseling Program on Stroke Care
Baik Kyun KIM ; Dong-Wan KANG ; Do Yeon KIM ; Jung Hyun PARK ; Ji-Seok WOO ; Young-Hee KIM ; Hyun-Sook KIM ; Min-Joo MOON ; Jeong-Yoon LEE ; Hyung Seok GUK ; Nakhoon KIM ; Sang-Won CHOI ; Hakyeu AHN ; Bosco Seong Kyu YANG ; Jun Yup KIM ; Jihoon KANG ; Moon-Ku HAN ; Hee-Joon BAE ; Beom Joon KIM
Health Policy and Management 2023;33(2):185-193
Background:
This study focuses on the establishment and operation of a stroke patient hotline program to help patients and their caregivers determine when acute neurological changes require emergency attention.Method: The stroke hotline was established at the Gyeonggi Regional Cerebrovascular Center, Seoul National University Bundang Hospital, in June 2016. Patients diagnosed with stroke during admission or in outpatient clinics were registered and provided with stroke education. Consulting nurses managed hotline calls and made decisions about outpatient schedules or emergency room referrals, consulting physicians when necessary. The study analyzed consultation records from June 2016 to December 2020, assessing consultation volumes and types. Outcomes and hotline satisfaction were also evaluated.
Results:
Over this period, 6,851 patients were registered, with 1,173 patients (18%) undergoing 3,356 hotline consultations. The average monthly consultation volume increased from 29.2 cases in 2016 to 92.3 cases in 2020. Common consultation types included stroke symptoms (22.3%), blood pressure/glucose inquiries (12.8%), and surgery/procedure questions (12.6%). Unexpected outpatient visits decreased from 103 cases before the hotline to 81 cases after. Among the 2,244 consultations between January 2019 and December 2020, 9.6% were recommended hospital visits, with two cases requiring intra-arterial thrombectomy. Patient satisfaction ratings of 9–10 points increased from 64% in 2019 to 69% in 2020.
Conclusion
The stroke hotline program effectively reduced unexpected outpatient visits and achieved high patient satisfaction.Expanding the program could enhance the management of stroke-related neurological symptoms and minimize unnecessary healthcare resource utilization.
9.Tumor Margin Infiltration in Soft Tissue Sarcomas: Prediction Using 3T MRI Texture Analysis
Minji KIM ; Won-Hee JEE ; Youngjun LEE ; Ji Hyun HONG, ; Chan Kwon JUNG ; Yang-Guk CHUNG ; So-Yeon LEE
Journal of the Korean Radiological Society 2022;83(1):112-126
Purpose:
To determine the value of 3 Tesla (T) MRI texture analysis for predicting tumor margin infiltration in soft tissue sarcomas.
Materials and Methods:
Thirty-one patients who underwent 3T MRI and had a pathologically confirmed diagnosis of soft tissue sarcoma were included in this study. Margin infiltration on pathology was used as the gold standard. Texture analysis of soft tissue sarcomas was performed on axial T1-weighted images (WI) and T2WI, fat-suppressed contrast-enhanced (CE) T1WI, diffusion-weighted images (DWI) with b-value of 800 s/mm², and apparent diffusion coefficient (ADC) was mapped. Quantitative parameters were compared between sarcomas with infiltrative margins and those with circumscribed margins.
Results:
Among the 31 patients with soft tissue sarcomas, 23 showed tumor margin infiltration on pathology. There were significant differences in kurtosis with the spatial scaling factor (SSF) of 0 and 6 on T1WI, kurtosis (SSF, 0) on CE-T1WI, skewness (SSF, 0) on DWI, and skewness (SSF, 2, 4) on ADC between sarcomas with infiltrative margins and those with circumscribed margins (p ≤ 0.046). The area under the receiver operating characteristic curve based on MR texture features for identification of infiltrative tumor margins was 0.951 (p < 0.001).
Conclusion
MR texture analysis is reliable and accurate for the prediction of infiltrative margins of soft tissue sarcomas.
10.Erratum: COVID-19 Molecular Testing in Korea:Practical Essentials and Answers From Experts Based on Experiences of Emergency Use Authorization Assays
Heungsup SUNG ; Kyoung Ho ROH ; Ki Ho HONG ; Moon-Woo SEONG ; Namhee RYOO ; Hyun Soo KIM ; Jaehyeon LEE ; So Yeon KIM ; Sook Won RYU ; Mi-Na KIM ; Myung Guk HAN ; Sang Won LEE ; Hyukmin LEE ; Cheon Kwon YOO ;
Annals of Laboratory Medicine 2021;41(1):126-127

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