Hyuk Soo Eun

Objectives: Metformin has been suggested to exert chemopreventive effects against gastric cancer. However, epidemiologic evidence remains inconsistent, and its impact on histologically confirmed precursor lesions, such as gastric dysplasia, remains unclear.Methods: We conducted a retrospective observational study of patients with type 2 diabetes who underwent endoscopic biopsy at a tertiary hospital in South Korea between 2009 and 2018. The patients were categorized into four groups based on the use of metformin and insulin. Histologic outcomes, including gastric dysplasia and adenocarcinoma, were evaluated using endoscopic biopsy specimens. Logistic regression and survival analyses were performed to assess the association between the use of antidiabetic medications and outcomes of gastric neoplasia.Results: Among 5269 patients with diabetes who underwent endoscopic biopsy, metformin use without insulin was associated with a lower incidence of gastric adenocarcinoma than non-metformin use. By contrast, insulin use was associated with a higher incidence of gastric malignancies. The occurrence of premalignant lesions, including gastric dysplasia and intestinal metaplasia, did not differ significantly between medication groups. These findings were consistent across logistic regression and survival analyses.Conclusions: Metformin use was associated with a reduced risk of gastric cancer in patients with diabetes who were not receiving insulin, but did not reduce the occurrence of gastric dysplasia. These results suggest that metformin exerts a stage-specific effect on gastric carcinogenesis, primarily by inhibiting the progression from dysplasia to invasive carcinoma, rather than preventing the initial development of precursor lesions.

DNA offers the promise of high-density, long-term storage, yet current systems face limitations due to polymerase chain reaction–based manual workflows that are inherently slow, error prone, and difficult to scale for practical applications. Here, we present an electric field–guided DNA pool elongation system that addresses these challenges through molecular data control. Our electric field–driven DNA memory chip integrates immobilization for encoding with reusable synthesis access capabilities. Electric field–driven primer access and DNA synthesis were evaluated through position-specific primer hybridization combined with elongation at room temperature, maintaining high fidelity while dramatically reducing access times. This electric field–driven approach exhibited linear degradation, projected to exceed 10 ⁵ reuse cycles. Using this method with a common primer, we successfully stored and retrieved different DNA pools, enabling one-step next-generation sequencing library preparation. We further retrieved a 0.2–megabyte three-dimensional object encoded in 1339 unique strands, achieving 96.6% perfect matching. The system demonstrates chip-level capacities approaching 1.1 × 10 ⁹ molecules per electrode, representing a significant advancement toward practical, scalable DNA data storage.

Background: Lateral margin positivity (LM+) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) may lead to residual disease and additional treatment. Subepithelial (SE) spread beneath normal mucosa has been suggested as a mechanism, but its association with LM+ is unclear. Methods: We retrospectively reviewed patients who underwent ESD for EGC from 2011 to 2021. Twenty-one LM+ cases were identified, and 227 LM– controls treated in 2019 were selected. Clinicopathologic and endoscopic factors were compared, and multivariate logistic regression was used to identify predictors. SE spread extent was evaluated pathologically. Results: Differentiation, Lauren classification, lesion size, and endoscopic color change were associated with LM+ in univariate analysis. Lesion size ≥ 2 cm was the only independent predictor. SE spread length was greater in LM+ cases than controls (5.80 ± 1.30 mm vs. 2.60 ± 2.36 mm, p = 0.004). SE spread ≥ 5 mm significantly increased the risk of LM+ (OR 15.077, 95% CI 1.550–146.670). Conclusions: SE spread—particularly when ≥5 mm—may contribute to LM+ by obscuring the true tumor boundary. Wider marking and resection margins may be considered in lesions with features suggesting SE spread.

Serum alpha-fetoprotein (AFP) is widely used for hepatocellular carcinoma (HCC) management, yet its limited sensitivity and specificity restrict diagnostic and prognostic utility. In this study, we explore the clinical potential of AFP quantification from cell-free DNA (cfDNA) and circulating tumor cells (CTCs) using a novel bead-based liquid biopsy platform. Following isolation, AFP abundance in cfDNA was quantified by qPCR, while AFP protein expression in CTCs was assessed via immunohistochemistry. Compared to serum AFP, cfDNA-derived AFP demonstrated significantly greater diagnostic accuracy in distinguishing HCC patients from non-cancerous individuals (p < 0.0001, AUC = 0.998), while AFP⁺ CTCs showed high specificity. Post-treatment changes in AFP levels from cfDNA and CTCs were significantly associated with therapeutic response and overall survival, outperforming conventional serum AFP. Longitudinal monitoring further revealed that cfDNA AFP levels reliably captured recurrence events prior to clinical diagnosis. Moreover, a combined metric integrating AFP levels from cfDNA and CTCs significantly improved response stratification (AUC = 0.89), outperforming individual biomarkers. This pilot study highlights the potential of multimodal AFP profiling through cfDNA and CTCs as a promising, non-invasive approach for enhancing diagnosis, prognosis, and treatment monitoring in HCC, with direct implications for personalized therapeutic strategies.

Cholecystectomy has been reported to be associated with an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD), but the extent and modifying factors of this association remain unclear. We analyzed 661,122 individuals enrolled from January 1, 2009 to December 31, 2019 in the Korean National Health Insurance Service-National Sample Cohort. Among them, 4,664 patients who underwent cholecystectomy were matched by age, sex, and other factors. MASLD was defined using a fatty liver index > 60. The cholecystectomy group had a 1.48-fold higher risk of MASLD compared to those without cholecystectomy. This risk was modified by the presence of underlying cardiometabolic risk factors. Compared to patients with fewer than three cardiometabolic risk factors and no cholecystectomy, the risk of MASLD increased 4.45-fold in patients with cholecystectomy and ≥ 3 cardiometabolic risk factors. In contrast, those with fewer than three risk factors showed only a 1.22-fold increase. Multivariate analysis including interaction terms showed an adjusted hazard ratio of 5.26 (95% CI, 2.35–11.78) for patients with cholecystectomy and ≥ 3 cardiometabolic risk factors. Cholecystectomy increases the risk of MASLD, particularly in individuals with multiple cardiometabolic risk factors. Comprehensive screening and aggressive management of these factors are essential before and after cholecystectomy.

OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease. Evidence indicates a relationship between sugar-sweetened beverage (SSB) consumption and MASLD development; however, the effects of specific SSB types on MASLD remain underexplored. This study investigated the association between consumption of 3 distinct types of SSBs and MASLD in Korean adults.METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey 2012-2016, including 8,310 participants aged 40-64 years. SSB consumption (soft drinks, fruit drinks, and Korean traditional drinks) was assessed using a food frequency questionnaire. MASLD was defined as a hepatic steatosis index ≥36 in the presence of any cardiometabolic risk factor. Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for relevant covariates.RESULTS: Compared to non-drinkers, consumption of soft drinks (≥3 serving/wk) was associated with higher odds of MASLD (OR, 1.36; 95% CI, 1.02 to 1.81; p for trend=0.03), while consumption of Korean traditional drinks (≥3 serving/wk) was associated with lower odds of MASLD (OR, 0.63; 95% CI, 0.45 to 0.89; p for trend=0.01). No association was found between fruit drink consumption and MASLD. In sex-stratified analysis (p-interaction=0.38), an inverse association between Korean traditional drinks and MASLD was observed in male (OR, 0.57; 95% CI, 0.34 to 0.95; p for trend=0.03), but not in female (OR, 0.72; 95% CI, 0.45 to 1.14; p for trend=0.17).CONCLUSIONS: Consuming soft drinks at least 3 times per week was positively associated with MASLD, whereas an equivalent intake of Korean traditional drinks was inversely associated with MASLD.

Jae Yoon Jeong, Su Jong Yu, Jeayeon Park, Na Ryung Choi, Soon Sun Kim, Jae Hyun Yoon, Hyuk Soo Eun, Jonggi Choi, Ki Tae Yoon, Young Kul Jung, Soo Young Park, Geum-Youn Gwak, Tae Yeob Kim, Dong Yun Kim, Do Young Kim, Ji Hoon Kim, Jin-Woo Lee, Jeong Won Jang. Gut and Liver -0001;0:. https://doi.org/10.5009/gnl240581

Glutamate, a crucial player in hepatic amino acid metabolism, has been relatively unexplored in immune cell activation. We show in a study with male mice that hepatic glutamate accumulates in vesicles of perivenous hepatocytes through vesicular glutamate transporter 3 (VGLUT3), regulated by the aryl hydrocarbon receptor upon chronic alcohol intake. Additional binge drinking triggers the exocytosis of glutamate by altering the intracellular Ca²⁺ level, stimulating metabotropic glutamate receptor 5 (mGluR5) and subsequent NADPH oxidase 2 (NOX2)-mediated ROS production in Kupffer cells (KCs). This interaction between hepatocytes and KCs is facilitated by pseudosynapse formation, arising from alcohol-induced ballooning of perivenous hepatocytes. Genetic or pharmacological interference of mGluR5 or NOX2 in KCs alleviates alcohol-related steatohepatitis (ASH). Analysis of patient samples confirmed some of the findings from mice, showing that plasma glutamate concentration and VGLUT3 levels correlate with ASH development. Conclusively, our findings highlight glutamate storage and release in mediating ASH, particularly through the pseudosynapse between hepatocytes and KCs.