1.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.
2.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.
3.Fecal Microbial Dysbiosis Is Associated with Colorectal Cancer Risk in a Korean Population
Jeongseon KIM ; Madhawa GUNATHILAKE ; Hyun Yang YEO ; Jae Hwan OH ; Byung Chang KIM ; Nayoung HAN ; Bun KIM ; Hyojin PYUN ; Mi Young LIM ; Young-Do NAM ; Hee Jin CHANG
Cancer Research and Treatment 2025;57(1):198-211
Purpose:
The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking.
Materials and Methods:
In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2.
Results:
There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples.
Conclusion
Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.
4.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
5.Effect of 50-Hz Filters on Pattern Electroretinogram
Dong Hee HA ; Nam Ju MOON ; Ungsoo Samuel KIM
Korean Journal of Ophthalmology 2025;39(3):241-245
Purpose:
Pattern electroretinogram (PERG) is used to evaluate the function of retinal ganglion cells. However, the amplitude of PERG is quite small, making the examination challenging to perform. Waveform noise may be minimized by applying various filters. We aimed to investigate the effect of 50-Hz filters on PERG test results.
Methods:
This is the retrospective observational study. PERG tests were performed using the RETI-scan system according to the International Society for Clinical Electrophysiology of Vision guidelines. Three types of 50-Hz filters (soft, middle, and hard) were applied. The differences in parameters (N35 peak time, P50 peak time, N95 peak time, P50 amplitude, N95 amplitude, and N95 to P50 ratio) were analyzed. Based on the provided normal range, the changes from normal to abnormal range or vice versa were investigated.
Results:
A total of 24 waveforms were analyzed. After filtering, the P50 and N95 amplitudes showed a significant reduction of 8% to 15% (P50 amplitude: 5.1 ± 2.7 μV without filter, 4.6 ± 2.3 μV with 50-Hz soft filter, 4.3 ± 2.1 μV with 50-Hz middle filter, 4.3 ± 2.1 μV with 50-Hz hard filter; N95 amplitude: 7.2 ± 4.2 μV without filter, 6.6 ± 3.8 μV with 50-Hz soft filter, 6.3 ± 3.6 μV with 50-Hz middle filter, 6.1 ± 3.6 μV with 50-Hz hard filter). This pattern was more prominent in normal subjects. All latencies except the N35 peak time exhibited no differences between the tests. The N95 to P50 ratio decreased after 50-Hz middle and hard filtering. Considering the normative data, switching between normal and abnormal results was rare.
Conclusions
Although peak time was not significantly affected, amplitude was significantly reduced after using 50-Hz filters. Thus, 50-Hz filters can smoothen the waveform. Nevertheless, caution must be exercised while taking readings.
6.Radiologic evolution of biopsy-proven acute interstitial nephritis: a multimodal imaging case report
Euljo JEONG ; Bong Soo PARK ; Il Hwan KIM ; Jung Hee SON ; Kyung Han NAM ; Yoon Ho LEE ; Yoo Jin LEE
Kosin Medical Journal 2025;40(1):72-79
This report presents radiologic changes after clinical improvement in a patient with acute interstitial nephritis (AIN). A 45-year-old female patient was referred for decreased renal function. Eight months prior, she had undergone hysterectomy and received chemotherapy. At the start of chemotherapy, her baseline creatinine level was 0.55 mg/dL, which rose to 1.46 mg/dL. Multiple imaging modalities performed when decreased renal function was observed revealed bilateral renal enlargement with increased cortical attenuation on computed tomography (CT), cortical hyperechogenicity on ultrasonography, and diffusion restriction in the renal cortices on magnetic resonance imaging. A renal biopsy was performed, and AIN was diagnosed. Follow-up laboratory tests showed that kidney function had improved to normal levels, and CT at that time showed a reduction in the size of both kidneys. Radiologic changes can serve as clues for the diagnosis of AIN. This is the first report to confirm radiological changes after the clinical improvement of AIN, thereby providing novel information about the course of AIN.
7.Impact of Metabolic Health and Its Changes on Erosive Esophagitis Remission: A Cohort Study
Nam Hee KIM ; Yoosoo CHANG ; Seungho RYU ; Chong Il SOHN
Journal of Neurogastroenterology and Motility 2025;31(1):54-62
Background/Aims:
We aim to compare the remission of erosive esophagitis (EE) among individuals with different phenotypes based on their metabolic health and obesity status and investigate the impact of changes in metabolic health on the EE remission.
Methods:
Asymptomatic adults (n = 16 845) with EE at baseline, who underwent follow-up esophagogastroduodenoscopy (EGD) were categorized into 4 groups as follows: metabolically healthy (MH) nonobese, metabolically unhealthy (MU) nonobese, MH obese, and MU obese. EE was defined as grade A or higher mucosal breaks observed using esophagogastroduodenoscopy.
Results:
During a median follow-up of 2.2 years, the remission rates of EE were 286.4/10 3 , 260.1/10 3 , 201.5/10 3 , and 219.9/10 3 person-years in MH nonobese, MU nonobese, MH obese, and MU obese groups, respectively. Multivariate-adjusted hazard ratios (95% CI) for EE remission among the MH nonobese, MU nonobese, and MH obese groups versus that of the MU obese group were 1.30 (1.23-1.37), 1.17 (1.12-1.23), and 0.98 (0.90-1.06), respectively, whereas those of the persistent MH, progression of MH to MU, and remission of MU to MH compared with the persistent MU group were 1.37 (1.23-1.52), 1.15 (1.01-1.30), and 1.28 (1.12-1.46), respectively.Increased EE remission in the persistent MH group was consistently observed in individuals with and without obesity (or abdominal obesity).
Conclusions
Metabolic health and nonobesity independently and favorably impact EE remission. Maintaining normal weight and healthy metabolic status may contribute to EE remission.
8.Switch to Rosuvastatin Plus Ezetimibe From Statin Monotherapy to Achieve Target LDL-Cholesterol Goal: A Multi-Center, Open-Label, Single-Arm Trial
Hong-Kyun PARK ; Jong-Ho PARK ; Hee-Kwon PARK ; Kyusik KANG ; Keun-Hwa JUNG ; Beom Joon KIM ; Jin-Man JUNG ; Young Seo KIM ; Yong-Seok LEE ; Hyo Suk NAM ; Yeonju YU ; Juneyoung LEE ; Keun-Sik HONG
Journal of Stroke 2025;27(2):275-278
9.Publication Trends in the Official Journals of Pediatric Dentistry Societies from 2004 to 2023
Joon Young KOO ; Yong Kwon CHAE ; Mi Sun KIM ; Ok Hyung NAM ; Sung Chul CHOI ; Hyo-Seol LEE
Journal of Korean Academy of Pediatric Dentistry 2025;52(1):46-60
This study explored the evolving trends in pediatric dentistry research, focusing on the changes in research trends in the Journal of the Korean Academy of Pediatric Dentistry (JKAPD) and comparing them with those in other international journals and previous studies. We selected the JKAPD (Korea), Pediatric Dentistry (PD, USA), European Archives of Paediatric Dentistry (EAPD, Europe), and The Japanese Journal of Pediatric Dentistry (JJPD, Japan) as subjects for this study, as each one is considered the core academic journals of the corresponding region. Data from the four journals were collected by reviewing articles published over 20 years from 2004 to 2023. Sixteen classification criteria were established, and 4,231 papers were assigned a classification number. This study included 1,205 studies from the JKAPD, 1,320 from the PD, 1,070 from the EAPD, and 636 from the JJPD. Publication trends were similar across the pediatric dental journals; however, the JJPD showed no correlation with other journals. Dental caries and prevention of dental caries were the most published topics in all journals (15.4%), followed by systemic diseases or patients with special health care needs (9.9%), conservative treatment and restorative materials (9.2%), and dental growth and developmental disturbances (8.8%). The thematic distribution of articles in the JKAPD observed in this study is consistent with that of previous studies. Although there were regional variations, the distribution of publication trends did not significantly change before or after the 21st century. This study offers valuable insights for comparing and analyzing trends in domestic and international research and providing an opportunity to examine which social and environmental changes have influenced these trends.
10.Efficacy of Automatic Suction-Type Sonic Toothbrush and Manual Toothbrush in Preschool Children: A Randomized, Controlled Crossover Pilot Study
Su Bin LEE ; Yong Kwon CHAE ; Mi Sun KIM ; Ok Hyung NAM ; Hyo-Seol LEE ; Sung Chul CHOI ; Ko Eun LEE
Journal of Korean Academy of Pediatric Dentistry 2025;52(2):181-192
This study investigated the plaque removal efficacy of a suction-type sonic toothbrush compared to a conventional manual toothbrush in preschool children aged 30 to 59 months. Using a randomized, double-blind, crossover design with a 2-week washout period, 20 pediatric participants were allocated to two study phases, each using either the suction-type sonic toothbrush or the manual toothbrush with caregiver assistance. The plaque removal effectiveness was assessed through the Silness and Löe plaque index and quantitative light-induced fluorescence values, including ΔR30 and ΔR120 indicators of plaque index. The result showed no statistically significant differences in plaque removal efficacy between the two toothbrushes, although both showed similar improvements. Caregiver feedback revealed high acceptability of the suction-type sonic toothbrush due to its convenience and engaging features, such as a light and suction function, which enhanced the tooth brushing experience. Although limited by the short follow-up period and small sample size, the findings suggest that suction-type sonic toothbrushes may offer practical benefits for young children requiring caregiver assistance.

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