1.MHY5456, an FXR Agonist, Ameliorates Hepatic Steatosis and Fibrosis in a Mouse Model of MASLD
Mi-Jeong KIM ; Hyejin KANG ; Jian YOO ; Sugyeong HA ; Jeongwon KIM ; Byeong Moo KIM ; Da Eun PARK ; Hae Young CHUNG ; Donghwan KIM ; Hyung Ryong MOON ; Ki Wung CHUNG
Biomolecules & Therapeutics 2026;34(3):652-665
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global health issue due to its increasing prevalence associated with lifestyle changes and its strong correlation with metabolic syndrome. Farnesoid X receptor (FXR) is a nuclear receptor that plays a pivotal role in regulating bile acid, lipid, and glucose metabolism, making it an attractive therapeutic target for liver and metabolic diseases. In this study, we investigated the effects of MHY5456, a synthetic agonist of FXR, on hepatic metabolism and fibrosis. MHY5456 enhanced the transcriptional activity of FXR in a concentration-dependent manner.Treatment of AC2F rat liver-derived cells with MHY5456 resulted in the downregulation of genes involved in lipid accumulation and an upregulation of mitochondrial-related gene expression. Additionally, MHY5456 significantly reduced oleic acid (OA)-induced lipid accumulation. To assess its anti-fibrotic potential, we tested its effects on transforming growth factor-beta (TGF-β)-induced fibrosis in LX2 human hepatic stellate cells (HSCs). MHY5456 significantly suppressed the expression of fibrosis-related genes and proteins. In vivo, administration of MHY5456 to mice fed a methionine-choline-deficient (MCD) diet alleviated hepatic fibrosis, inflammation, and lipid accumulation. These results show that FXR activation by MHY5456 modulates lipid metabolism and fibrotic pathways, suggesting its potential as a pharmacological candidate for liver and metabolic disorders, including MASLD. Further pharmacological and toxicological studies are needed to confirm its therapeutic relevance.
2.Gastrointestinal Surgery Status and the Risks of Ischemic Stroke and Safety Outcomes With Direct Oral Anticoagulants Versus Warfarin in Atrial Fibrillation: A Nationwide Population-Based Cohort Study
Jiyeon HA ; Wookjin YANG ; Mi-Sook KIM ; Eung-Joon LEE ; Matthew CHUNG ; Boyeon YANG ; Hyemin JANG ; Jeong-Min KIM ; Keun-Hwa JUNG ; Seung-Hoon LEE
Journal of Stroke 2026;28(2):228-239
Background:
and Purpose Although gastrointestinal (GI) surgery can affect drug efficacy, its impact on oral anticoagulants (OACs) remains unclear. This study investigated the impact of GI surgery on the comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation (AF).
Methods:
Using a nationwide South Korean claims database, AF patients prescribed OACs between 2015 and 2021 were analyzed. The primary outcome was ischemic stroke, and secondary outcomes were major bleeding, all-cause death, and composite outcome (ischemic stroke, major bleeding, all-cause death). Outcomes were compared by OAC type (DOAC vs. warfarin) and GI surgery status using inverse probability of treatment weighting and a Fine–Gray subdistribution hazard model with time-varying covariates.
Results:
Among 388,214 AF patients (mean age, 71.9 yr; 42.7% male), 6,907 (1.8%) underwent GI surgery. The effect of GI surgery differed between warfarin and DOACs for ischemic stroke (Pint= 0.018), with increased risk for warfarin (adjusted HR [aHR]: 2.32; 95% confidence interval [CI] 1.17–4.62), but not for DOACs (aHR: 0.97 [95% CI 0.77–1.22]) after surgery. Effects of surgery on major bleeding, all-cause death, and composite outcome did not differ. In post–GI surgery setting, DOACs demonstrated lower ischemic stroke risk (aHR: 0.35 [95% CI 0.17–0.72]) and comparable risks for other outcomes. Exploratory analyses by surgery location suggested a more favorable profile of DOACs after upper GI surgery.
Conclusions
In AF patients, GI surgery significantly increased ischemic stroke risk among warfarin users, but not among DOAC users. DOACs showed generally favorable profiles after GI surgery and may remain a reasonable anticoagulant, with potentially more favorable profile after upper GI surgery.
3.Radiofrequency Ablation for Recurrent Thyroid Cancers:2025 Korean Society of Thyroid Radiology Guideline
Eun Ju HA ; Min Kyoung LEE ; Jung Hwan BAEK ; Hyun Kyung LIM ; Hye Shin AHN ; Seon Mi BAEK ; Yoon Jung CHOI ; Sae Rom CHUNG ; Ji-hoon KIM ; Jae Ho SHIN ; Ji Ye LEE ; Min Ji HONG ; Hyun Jin KIM ; Leehi JOO ; Soo Yeon HAHN ; So Lyung JUNG ; Chang Yoon LEE ; Jeong Hyun LEE ; Young Hen LEE ; Jeong Seon PARK ; Jung Hee SHIN ; Jin Yong SUNG ; Miyoung CHOI ; Dong Gyu NA ;
Korean Journal of Radiology 2025;26(1):10-28
Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.
4.Radiofrequency Ablation for Recurrent Thyroid Cancers:2025 Korean Society of Thyroid Radiology Guideline
Eun Ju HA ; Min Kyoung LEE ; Jung Hwan BAEK ; Hyun Kyung LIM ; Hye Shin AHN ; Seon Mi BAEK ; Yoon Jung CHOI ; Sae Rom CHUNG ; Ji-hoon KIM ; Jae Ho SHIN ; Ji Ye LEE ; Min Ji HONG ; Hyun Jin KIM ; Leehi JOO ; Soo Yeon HAHN ; So Lyung JUNG ; Chang Yoon LEE ; Jeong Hyun LEE ; Young Hen LEE ; Jeong Seon PARK ; Jung Hee SHIN ; Jin Yong SUNG ; Miyoung CHOI ; Dong Gyu NA ;
Korean Journal of Radiology 2025;26(1):10-28
Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.
5.Radiofrequency Ablation for Recurrent Thyroid Cancers:2025 Korean Society of Thyroid Radiology Guideline
Eun Ju HA ; Min Kyoung LEE ; Jung Hwan BAEK ; Hyun Kyung LIM ; Hye Shin AHN ; Seon Mi BAEK ; Yoon Jung CHOI ; Sae Rom CHUNG ; Ji-hoon KIM ; Jae Ho SHIN ; Ji Ye LEE ; Min Ji HONG ; Hyun Jin KIM ; Leehi JOO ; Soo Yeon HAHN ; So Lyung JUNG ; Chang Yoon LEE ; Jeong Hyun LEE ; Young Hen LEE ; Jeong Seon PARK ; Jung Hee SHIN ; Jin Yong SUNG ; Miyoung CHOI ; Dong Gyu NA ;
Korean Journal of Radiology 2025;26(1):10-28
Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.
6.Radiofrequency Ablation for Recurrent Thyroid Cancers:2025 Korean Society of Thyroid Radiology Guideline
Eun Ju HA ; Min Kyoung LEE ; Jung Hwan BAEK ; Hyun Kyung LIM ; Hye Shin AHN ; Seon Mi BAEK ; Yoon Jung CHOI ; Sae Rom CHUNG ; Ji-hoon KIM ; Jae Ho SHIN ; Ji Ye LEE ; Min Ji HONG ; Hyun Jin KIM ; Leehi JOO ; Soo Yeon HAHN ; So Lyung JUNG ; Chang Yoon LEE ; Jeong Hyun LEE ; Young Hen LEE ; Jeong Seon PARK ; Jung Hee SHIN ; Jin Yong SUNG ; Miyoung CHOI ; Dong Gyu NA ;
Korean Journal of Radiology 2025;26(1):10-28
Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.
7.Radiofrequency Ablation for Recurrent Thyroid Cancers:2025 Korean Society of Thyroid Radiology Guideline
Eun Ju HA ; Min Kyoung LEE ; Jung Hwan BAEK ; Hyun Kyung LIM ; Hye Shin AHN ; Seon Mi BAEK ; Yoon Jung CHOI ; Sae Rom CHUNG ; Ji-hoon KIM ; Jae Ho SHIN ; Ji Ye LEE ; Min Ji HONG ; Hyun Jin KIM ; Leehi JOO ; Soo Yeon HAHN ; So Lyung JUNG ; Chang Yoon LEE ; Jeong Hyun LEE ; Young Hen LEE ; Jeong Seon PARK ; Jung Hee SHIN ; Jin Yong SUNG ; Miyoung CHOI ; Dong Gyu NA ;
Korean Journal of Radiology 2025;26(1):10-28
Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.
8.Single-cell RNA sequencing revealed the role of the Th17 pathway in the development of anti- human leukocyte antigen antibodies in a highly sensitized mouse model
Hanbi LEE ; Yoo-Jin SHIN ; Xianying FANG ; Sheng CUI ; Sun Woo LIM ; Seon-Yeong LEE ; Sang Hun EUM ; Ji-Won MIN ; Chang-Won HONG ; Hae-Ock LEE ; Mi-La CHO ; Eun-Jee OH ; Chul Woo YANG ; Byung Ha CHUNG
Kidney Research and Clinical Practice 2025;44(6):960-973
Background:
The aim of this study is to investigate the specific pathway involved in human leukocyte antigen (HLA) sensitization using single-cell RNA-sequencing analysis and an allo-sensitized mouse model developed with an HLA.A2 transgenic mouse.
Methods:
For sensitization, wild-type C57BL/6 mouse received two skin grafts from C57BL/6-Tg(HLA-A2.1)1Enge/J mouse (allogeneic mouse, ALLO). For syngeneic control (SYN), skin grafts were transferred from C57BL/6 to C57BL/6. We performed single-cell RNA-sequencing analysis on splenocytes isolated from ALLO and SYN and compared the gene expression between them.
Results:
We generated 9,190 and 8,890 single-cell transcriptomes from ALLO and SYN, respectively. Five major cell types (B cells, T cells, natural killer cells, macrophages, and neutrophils) and their transcriptome data were annotated according to the representative differentially expressed genes of each cell cluster. The percentage of B cells was higher in ALLO than it was in SYN. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the highly expressed genes in the B cells from ALLO were mainly associated with antigen processing and presentation pathways, allograft rejection, and the Th17 cell differentiation pathway. Upregulated genes in the T cells of ALLO were involved in the interleukin (IL)-17 signaling pathway. The ratio of Th17 cluster and Treg cluster was increased in the ALLO. On flow cytometry, the percentage of Th17 (IL-17+/CD4+ T) cells was higher and regulatory T cells (FOXP3+/CD4+ T) was lower in the ALLO compared to those in the SYN.
Conclusion
Our results indicate that not only the B cell lineage but also the Th17 cells and their cytokine (IL-17) are involved in the sensitization to HLA.
9.DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice
Hong Min KIM ; Mi-Hye KWON ; Eun Soo LEE ; Kyung Bong HA ; Choon Hee CHUNG
Journal of Yeungnam Medical Science 2024;41(2):103-112
Background:
Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation.
Methods:
Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW264.7 cells.
Results:
DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8+ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages.
Conclusion
Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.
10.Pharmacological properties of Technekitty injection (Tc-99m) in diagnosing feline hyperthyroidism
Jae Cheong LIM ; So-Young LEE ; Eun Ha CHO ; Yu Mi JUNG ; Ki Hwan PARK ; Young Uk PARK ; Sung Soo NAM ; Tae Hoon LEE ; Jae Won LEE ; Jisu SUN ; Hye Kyung CHUNG ; Yong Jin LEE ; Yeon CHAE ; Byeong-Teck KANG
Journal of Biomedical and Translational Research 2024;25(4):185-199
Thyroid scanning using technetium-99m ( 99mTc) is the gold standard for diagnosing feline hyperthyroidism. In cats with an overactive thyroid, a thyroid scan is the most appropriate imaging technique to detect and localize any hyperfunctional adenomatous thyroid tissue. In this study, the pharmacological properties of the Technekitty injection (Tc-99m), developed as a diagnostic agent for feline hyperthyroidism using 99mTc as an active ingredient, were tested in FRTL-5 thyroid follicular cell line and ICR mice. The percentage of cell uptake of the Tc-99m in FRTL-5 thyroid cells was 0.182 ± 0.018%, which was about 6 times higher compared to Clone 9 hepatocytes. This uptake decreased by 38.2% due to competitive inhibition by iodine (sodium iodide). In tissue distribution tests by using ICR mice, the highest distribution was observed in the liver, kidneys, spleen, lungs, and femur at 0.083 hours after administration, and this distribution decreased as the compound was excreted through the kidneys, the pri-mary excretory organ. Maximum distribution was confirmed at 1 hour in the small intestine, 6hours in the large intestine, and 2 hours in the thyroid gland. Additionally, the total amount excreted through urine and feces over 48 hours (2 days) was 78.80% of the injected dose, with 37.70% (47.84% of the total excretion) excreted through urine and 41.10% (52.16% of the total excretion) through feces. In conclusion, the Tc-99m has the same mechanism of action, potency, absorption, distribution, metabolism, and excretion characteristics as 99mTc used for feline hyperthyroidism in the United States, Europe, and other countries, because the Technekitty injection (Tc-99m) contains 99mTc as its sole active ingredient. Based on these results, the Technekitty injection (Tc-99m) is expected to be safely used in the clinical diagnosis of feline hyperthyroidism.

Result Analysis
Print
Save
E-mail