Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

A phytochemical study of the root extract of Hemerocallis fulva var. kwanso Regel resulted in the isolation and structural characterization of four lignans (1‒4), three flavanones (5, 6, and 8), one chalcone (9), and two monoterpenes (7 and 10). Enzyme inhibition assays revealed that two flavanone glucosides (5 and 6) showed significant inhibitory effect against protein tyrosine phosphatase 1B (PTP1B), with IC50 values of 31.38 µM and 51.46 µM, respectively. Further enzyme kinetic studies demonstrated that these two compounds acted as noncompetitive PTP1B inhibitors, with Ki values of 30.88 µM and 50.38 µM, respectively.

Dystaenia takeshimana (Nakai) Kitagawa belongs to the family Apiaceae (Umbelliferae) and is a perennial herb naturally endemic to Ulleung Island, Republic of Korea. Following its successful introduction and cultivation in mainland Korea, a phytochemical investigation of this plant was carried out. As a result, thirteen compounds were isolated and structurally characterized, including one flavonoid glycoside (1), two polyacetylenes (2 and3), one caffeoylquinic acid derivative (4), one aliphatic hydroxy acid (5), four phenolic acids and their derivatives(6, 8–10), one aromatic alcohol derivative (7), two carbohydrates (11 and 12), and one phytosterol (13). The structures of these compounds were elucidated based on spectroscopic analyses and comparison with previously reported literature data. To the best of our knowledge, this study represents the first report on the isolation of falcarinol (2), trans-4-hydroxy-2-nonenoic acid (5), and sucrose (11) from D. takeshimana and the evaluation of their protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Compounds 2, 3, and 5 exhibited potent PTP1B inhibitory effects with IC50 values of 10.74, 8.31, and 25.24 µM, respectively. Enzyme kinetic studies indicated noncompetitive inhibition by 2 and mixed-type inhibition by 5 against PTP1B. Furthermore, molecular docking analysis was performed to investigate the binding interactions between the active compounds and the enzyme active site.

Phytochemical investigation of the water extract and alkaloid fraction of Areca catechu L. led to theisolation of one new methoxyflavonoid rutinoside (1), together with eleven known compounds (2−12), five of which (8−12) belong to the pyridine alkaloid class. The structure of the new compound was elucidated through extensive spectroscopic analyses, including 1D and 2D NMR experiments and high-resolution mass spectrometry.Notably, rhamnazin-3-O-rutinoside (2) is reported here for the first time from this species. The isolated compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) using a p-nitrophenyl phosphate assay. Flavonoids (3 and 4) and stilbene (5) exhibited notable inhibitory activity, with IC50 values of 13.30 ± 0.71, 13.44 ± 0.84, and 8.68 ± 0.12 μM, respectively. In contrast, methoxyflavonoid rutinosides (1 and 2) and pyridine alkaloids (8−12) did not show significant inhibitory activity against PTP1B.These findings provide additional chemical insights into A. catechu and its constituents in relation to PTP1B inhibition.

Purpose: We aimed to investigate how genetic predisposition to drinking and gastric cancer (GC) modifies the association between alcohol consumption and GC risk in the Korean population. Materials and Methods: Polygenic risk scores for GC (PRS-GC) and alcohol consumption (PRS-Alcohol) were formulated using genome-wide association results from BioBank Japan. Validation was performed using Korean cohorts (SNUBH-GENIE cohort), incorporating 8,846 controls and 531 patients with GC. Subsequently, these PRSs were applied to an independent Korean cohort of 67,771 participants, including 313 patients with GC during the follow-up for 14 years (KoGES cohort). Results: In KoGES cohort, the influence of alcohol consumption on GC risk was significantly altered by the PRS-GC and exhibited a synergistic interaction effect. PRS-Alcohol itself shows a negative correlation with GC risk. However, when actual alcohol consumption significantly exceeded genetically predicted levels, the risk of alcohol-related GC was notably increased (adjusted hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.72). Heavy drinkers in the high–PRS-GC/low–PRS-Alcohol group had a 2.16 times higher risk of GC than non-to-light drinkers, which was prominent in males. Conclusion Korean drinkers with higher PRS-GC who consume alcohol more than genetically predicted levels are susceptible to GC. PRS-GC and PRS-Alcohol may be beneficial for assessing the impact of alcohol consumption on GC risk in Koreans.

suggest that some reproductive factors associated with BC differ across ethnicities and time trends, perhaps due to the prevalence of reproductive factors and the baseline hazard of BC.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

The roots of Astragalus membranaceus Bunge have long been used in herbal medicine for their diversebiological activities. Notably, its potential anti-diabetic properties have been extensively studied, highlighting promising therapeutic prospects. In this study, we conducted a comprehensive investigation focusing on flavonoid components from the roots of A. membranaceus and their PTP1B inhibitory activity. As a result, we isolated a total of 24 flavonoids, among which formonentin (1), pratensein (3), and vesticarpan (19) emerged as the most potent inhibitors against PTP1B with IC50 value of 10.9 ± 1.09 μM, 10.0 ± 1.71 μM, and 10.3 ± 1.31 μM, respectively.Additionally, through the enzyme kinetic analysis, the inhibition mode of compound 19 was determined as a competitive inhibitor, with Ki value of 7.6 ± 1.17 μM. Furthermore, the molecular docking simulation elucidated the binding mechanism of compound 19 with PTP1B, mainly through van der Waals forces and hydrogen bonds.This study highlights the PTP1B inhibitory potential of the flavonoid constituents derived from the roots of A. membranaceus. Moreover, discovering vesticarpan (19) as a novel PTP1B inhibitor provides a significant foundation for further investigations to develop innovative therapeutic strategies for diabetes treatment.

Patients with ectodermal dysplasia often have atrophied alveolar bone and an inadequate maxillomandibular relationship owing to congenital edentulism.Accurate implant placement that can overcomes anatomical limitations and orthognathic surgery to improve the maxillomandibular relationship is necessary for creating implant-supported prosthesis for these patients. Implant placement and provisional prosthesis fabrication before orthognathic surgery can provide critical fixed reference points and ensure accuracy during orthognathic surgery.In our patient, a digital system was used to design a surgical guide that considered the predictable position of the definitive prosthesis, allowing the placement of implants to overcome anatomical limitations and the creation of fixed reference points via the delivery of a provisional prosthesis for effective orthognathic surgery. The lack of compensation during orthognathic surgery was considered in the definitive prosthesis. As a result, a prosthesis with a minimal anterior cantilever was fabricated. This study aimed to determine the appropriate sequence of multidisciplinary collaborations that would, result in the best functional and aesthetic outcomes.