1.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
2.Clinical Significance of Various Pathogens Identified in Patients Experiencing Acute Exacerbations of COPD: A Multi-center Study in South Korea
Hyun Woo JI ; Soojoung YU ; Yun Su SIM ; Hyewon SEO ; Jeong-Woong PARK ; Kyung Hoon MIN ; Deog Kyeom KIM ; Hyun Woo LEE ; Chin Kook RHEE ; Yong Bum PARK ; Kyeong-Cheol SHIN ; Kwang Ha YOO ; Ji Ye JUNG
Tuberculosis and Respiratory Diseases 2025;88(2):292-302
Background:
Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD.
Methods:
This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests.
Results:
Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030).
Conclusion
This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.
3.Association of Nutritional Intake with Physical Activity and Handgrip Strength in Individuals with Airflow Limitation
I Re HEO ; Tae Hoon KIM ; Jong Hwan JEONG ; Manbong HEO ; Sun Mi JU ; Jung-Wan YOO ; Seung Jun LEE ; Yu Ji CHO ; Yi Yeong JEONG ; Jong Deog LEE ; Ho Cheol KIM
Tuberculosis and Respiratory Diseases 2025;88(1):120-129
Background:
We investigated whether nutritional intake is associated with physical activity (PA) and handgrip strength (HGS) in individuals with airflow limitation.
Methods:
This study analyzed data from the 2014 and 2016 Korean National Health and Nutrition Examination Survey. We assessed total protein intake (g/day), caloric intake (kcal/day), and other nutritional intakes, using a 24-hour dietary recall questionnaire. HGS was measured three times for each hand using a digital grip strength dynamometer, and PA was assessed as health-enhancing PA. Airflow limitation was defined as a forced expiratory volume/forced vital capacity ratio of 0.7 in individuals over 40 years of age. Participants were categorized into groups based on their PA levels and HGS measurements: active aerobic PA vs. non-active aerobic PA, and normal HGS vs. low HGS.
Results:
Among the 622 individuals with airflow limitation, those involved in active aerobic PA and those with higher HGS had notably higher total food, calorie, water, protein, and lipid intake. The correlations between protein and caloric intake with HGS were strong (correlation coefficients=0.344 and 0.346, respectively). The forest plots show that higher intakes of food, water, calories, protein, and lipids are positively associated with active aerobic PA, while higher intakes of these nutrients are inversely associated with low HGS. However, in the multivariate logistic regression analysis, no significant associations were observed between nutritional intake and active aerobic PA or HGS.
Conclusion
Nutritional intake was found to not be an independent factor associated with PA and HGS. However, the observed correlations suggest potential indirect effects that warrant further investigation.
4.Percutaneous Transpedicular Intravertebral Cage Augmentation with Short-Segment Fixation Using Specially Designed Cannulated Cage Trials for Advanced Kümmell Disease: A Preliminary Study Comparing with Vertebroplasty with Short-Segment Fixation
Sung Cheol PARK ; Gene CHEH ; Yongjung KIM ; Hoon-Jae CHUNG ; Min-Seok KANG ; Ji-Hye CHOI
Clinics in Orthopedic Surgery 2025;17(1):29-38
Background:
The treatment of Kümmell disease (KD) is controversial. Corpectomy and reconstruction or osteotomy with long-level fusion was traditionally performed for the advanced KD. However, these procedures can be disadvantageous for elderly patients.Several alternative surgical procedures including transpedicular intravertebral cage augmentation (TPICA) or vertebroplasty (VP) combined with short-segment fixation (SSF) have been suggested to minimize the surgical burden. This study aimed to compare the outcomes of percutaneous TPICA plus SSF with VP plus SSF for advanced thoracolumbar (T11–L2) KD and to introduce our novel percutaneous TPICA technique using specially designed cannulated cage trials.
Methods:
We devised specially designed cannulated cage trials to make the TPICA procedure safer and more reproducible, minimizing the risk of the pedicle medial wall violation. All consecutive patients who underwent percutaneous TPICA or VP combined with SSF for advanced thoracolumbar KD, from January 2021 to June 2022, with ≥ 1-year follow-up at a single institution, were included. Perioperative details, clinical outcomes (visual analog scale and Oswestry Disability Index), and radiological outcomes (anterior vertebral body compression percentage and vertebral kyphotic angle [VKA] of the fractured vertebra, and local Cobb angle [LCA]) were collected and compared between the groups.
Results:
A total of 42 patients were enrolled, with 21 patients in each group. There were no patients with pedicle medial wall fracture in the TPICA group. Both procedures provided significantly favorable radiological outcomes compared to those preoperatively. No significant differences were observed in the changes over time in all radiological parameters between the groups. Loss of correction during the follow-up period was significantly smaller in patients with TPICA than in those with VP in VKA (median [interquartile range], 2.15 [0.30–2.80] vs. 2.90 [0.90–6.53]; p = 0.030) and LCA (2.70 ± 2.90 vs. 5.17 ± 4.40, p = 0.037).
Conclusions
Both procedures are minimally invasive and useful options for advanced KD, especially for elderly patients with high comorbidity. Our novel percutaneous TPICA technique using cannulated cage trials, being safer and more reproducible, may allow spine surgeons to easily perform TPICA.
6.Triiodothyronine Is Associated with Incidence/Resolution of Steatotic Liver Disease: Longitudinal Study in Euthyroid Korean
Hye In KIM ; Jun Young KIM ; Jung Hwan CHO ; Ji Min HAN ; Sunghwan SUH ; Ji Cheol BAE ; Tae Hyuk KIM ; Sun Wook KIM ; Jong Ryeal HAHM ; Jae Hoon CHUNG
Endocrinology and Metabolism 2025;40(1):135-145
Background:
The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design.
Methods:
This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models.
Results:
During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD.
Conclusion
In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.
7.Investigating Human Liver Tissue-Resident Memory T Cells from the Perspectives of Gastroenterologists and Hepatologists
Gut and Liver 2025;19(2):161-170
Liver tissue-resident memory T (TRM ) cells play a pivotal role in hepatic immune responses. Theirunique residence within liver sinusoids allow continuous antigen surveillance. In this review, wehighlight the role of liver TRM cells in protective immunity and disease pathology. Comparisons between human and murine liver TRM cells reveal species-specific characteristics, suggesting the need for human-focused studies. One key finding is the involvement of liver TRM cells in viral hepatitis, where they can both control infection and contribute to liver damage. Liver TRM cellsalso exhibit dual roles in metabolic-associated steatotic liver disease, promoting inflammation and fibrosis while also contributing to fibrosis resolution. In autoimmune liver diseases, suchas autoimmune hepatitis and primary sclerosing cholangitis, the presence of liver TRM cells correlates with disease severity. In this review, we underscore the importance of liver TRM cells invaccine development, particularly vaccines against malaria. Future research should focus on themechanisms governing TRM -cell formation, maintenance, and function, with the aim of supportingtheir protective roles while mitigating detrimental effects. Advancing our understanding of liverTRM cells will enhance our knowledge of liver immunology and inform novel therapeutic strategiesfor liver disease management.
8.Taurine Synthesis by 2-Aminoethanethiol Dioxygenase as a Vulnerable Metabolic Alteration in Pancreatic Cancer
Hoonsik NAM ; Woohyung LEE ; Yun Ji LEE ; Jin-Mo KIM ; Kyung Hee JUNG ; Soon-Sun HONG ; Song Cheol KIM ; Sunghyouk PARK
Biomolecules & Therapeutics 2025;33(1):143-154
Pancreatic ductal adenocarcinoma (PDAC) exhibits an altered metabolic profile compared to normal pancreatic tissue. However, studies on actual pancreatic tissues are limited. Untargeted metabolomics analysis was conducted on 54 pairs of tumor and matched normal tissues. Taurine levels were validated via immunohistochemistry (IHC) on separate PDAC and normal tissues.Bioinformatics analysis of transcriptomics and proteomics data evaluated genes associated with taurine metabolism. Identified taurine-associated gene was validated through gene modulation. Clinical implications were evaluated using patient data. Metabolomics analysis showed a 2.51-fold increase in taurine in PDAC compared to normal tissues (n=54). IHC confirmed this in independent samples (n=99 PDAC, 19 normal). Bioinformatics identified 2-aminoethanethiol dioxygenase (ADO) as a key gene modulating taurine metabolism. IHC on a tissue microarray (39 PDAC, 10 normal) confirmed elevated ADO in PDAC. The ADOTaurine axis correlated with PDAC recurrence and disease-free survival. ADO knockdown reduced cancer cell proliferation and tumor growth in a mouse xenograft model. The MEK-related signaling pathway is suggested to be modulated by ADO-Taurine metabolism. Our multi-omics investigation revealed elevated taurine synthesis mediated by ADO upregulation in PDAC. The ADOTaurine axis may serve as a biomarker for PDAC prognosis and a therapeutic target.
9.Association of weight and dietary habits with high blood mercury levels in Korean adolescents: data from the KoNEHS cycle 4, 2018-2020
Ji Hoon KIM ; Minju JUNG ; Jaewon MUN ; Dong-Jae SEO ; Jong-Han LEEM ; Shin-Goo PARK ; Dong-Wook LEE ; Hyung Doo KIM ; Hwan-Cheol KIM
Annals of Occupational and Environmental Medicine 2025;37(1):e5-
Background:
Humans are exposed to mercury primarily in its highly toxic form, methyl mercury, which is known to have adverse effects on various organs and systems. The negative impact of mercury exposure on the growth, development, and mental health of children, from infancy to adolescence, is well-documented. However, there are no internationally standardized safe limits for mercury exposure. This study investigated the impact of dietary habits and higher body mass index (BMI) on blood mercury levels in adolescents.
Methods:
This study analyzed the data from the 4th Korean National Environmental Health Survey (KoNEHS) 2018–2020. The focus was on 825 middle and high school students aged 13–18 years, whose blood mercury levels were measured. A survey on dietary and lifestyle habits was also conducted. Blood mercury levels were categorized by geometric median values, and associations with overweight status and seafood consumption were examined using a generalized linear model.
Results:
The geometric mean blood mercury level for the entire sample was 1.37 μg/L, with levels of 1.31 μg/L in normal-weight individuals and 1.43 μg/L in overweight individuals, showing a statistically significant difference between the two groups. After adjusting for other variables, blood mercury levels were significantly associated with overweight status (estimate: 0.084; p = 0.018; 95% confidence interval [CI]: 0.015–0.153), consumption of large fish and tuna more than once a week (estimate: 0.18; p = 0.001; 95% CI: 0.077–0.284), and consumption of fish once a week or more (estimate: 0.147; p = 0.004; 95% CI: 0.043–0.250).
Conclusions
In adolescents, a higher BMI and an increased consumption of large fish, tuna, and fish were associated with higher blood mercury levels. Notably, a stronger association was found between large fish consumption and blood mercury levels in the overweight group. These findings suggest the need to moderate seafood consumption and establish more proactive mercury exposure standards for adolescents.
10.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

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