https://ir.ymlib.yonsei.ac.kr/handle/22282913/168808 Tue, 12 May 2026 21:52:56 GMT 2026-05-12T21:52:56Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211445 Title: Design, synthesis and biological evaluation of symmetric thiadiazole carboxamide derivative as glutaminase inhibitor Authors: Cyriac, Rajath; Lee, Eun Ji; Kwon, Yeongju; Yun, Mi Ran; Jung, Myoung Eun; Ahn, Sunjoo; Chae, Chang Hak; Choi, Gildon; Cho, Byoung Chul; Lee, Kwangho; 윤미란 Abstract: Metabolic reprogramming toward glutamine anaplerosis is a well-established vulnerability in tumors harboring co-occurring KRAS and KEAP1 mutations, creating a dependency on glutaminase (GLS)-mediated glutaminolysis for survival and growth. Although allosteric GLS inhibitors such as BPTES (Bis-2-(5-phenylacetamido-1,3,4thiadiazol-2-yl)ethyl sulfide) and later-generation analogs such as CB-839 (Telaglenastat) have pharmacologically validated this target, their clinical utility has been constrained by suboptimal drug-like properties, including poor solubility and bioavailability. To overcome these limitations, we developed TRG-192, a novel symmetric amidothiadiazole derivative engineered with a distinct chemical scaffold to enhance physicochemical and pharmacokinetic profiles. In vitro characterization revealed that TRG-192 is a potent GLS inhibitor (IC50 = 68 nM). This biochemical potency translated to a functional effect in a cellular model of glutamine dependence, as evidenced by a significant depletion of intracellular glutamate pools in LDK378-resistant (LR) cells. Furthermore, TRG-192 demonstrated a favorable preclinical safety profile in initial toxicological assessments. Collectively, these data-encompassing potent target engagement, functional on-target activity, and preliminary safety-provide a compelling rationale for the advancement of TRG-192 into in vivo efficacy studies. Wed, 01 Jul 2026 00:00:00 GMT https://ir.ymlib.yonsei.ac.kr/handle/22282913/211445 2026-07-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211442 Title: Slippery dopamine-fluoropolymer hybrid surface for improving biliary stent longevity Authors: Kim, Tae Young; Lee, Won-Jong; Lee, Yurim; Kim, Seo Jung; Min, Sungjin; Chung, Seyong; Kim, Soo A.; Yook, Keun-Young; Moon, Chang-Hwan; Lee, Yeontaek; Park, Kijun; Kim, Dae-Hyun; Seo, Jungmok Abstract: Biliary obstruction leads to bile retention and triggers a cascade of pathological events. Bile accumulation induces cholestasis and inflammation, progressing to hepatocellular injury, fibrosis, and ultimately liver failure. To restore bile flow, biliary stents are a necessary option due to their immediate patency. However, their high susceptibility to foreign body reaction (FBR) associated fibrosis, biofilm formation, and biliary sludge accumulation leads to frequent occlusion. To address this limitation, we developed the Enhanced Longevity by antifouling Functional coating for Stent (ELFS), a lubricant-infused coating that prevents stent occlusion. ELFS can be readily fabricated via a simple dip-coating solution process and employ a polydopamine (PDA) adhesion layer. Intravital imaging in mice confirmed that ELFS suppressed the FBR by blocking early neutrophil adhesion, which in turn prevented downstream immune-fibrotic cascades. At 3 h, neutrophil recruitment in the non-coated group was >20-fold higher than in ELFS-coated groups. Additionally, ELFS-coated stents remained free of biofilm for over six months in mice and maintained full open for two months in a rabbit common bile duct model. In contrast, non-coated stents resulted in complete occlusion, bile duct dilation (over 4 times), hepatomegaly (over 2 times), and fibrosis. Wed, 01 Jul 2026 00:00:00 GMT https://ir.ymlib.yonsei.ac.kr/handle/22282913/211442 2026-07-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/212116 Title: Continuity of care for patients with hypertension or diabetes mellitus reduced medical utilization, total medical costs, and cardiovascular events based on the Korean NHIS-HEALS cohort Authors: Yun, Eun-Kyeong; Shim, Jae Yong; Shin, Sang-Jun; Kang, Hee-Taik Abstract: Background and aim: Continuous care of chronic diseases can improve the efficiency of medical system. This study aims to investigate whether continuity of care (CoC) for hypertension or diabetes mellitus (DM) improves medical utilization, costs, and health outcomes, including cardiovascular diseases (CVDs). Methods and results: For this study, 14,246 hypertensive and 9382 diabetic patients aged 60 years or older from the Korean NHIS-HEALS cohort were included. CoC was categorized into three tertiles by disease and sex. Medical utilization and costs were compared using negative binomial regression models and Gamma regression models after adjusting for potential confounders. Cox proportional hazards regression models were constructed to examine the association between the CoC index and the health outcomes (all-cause mortality, CVDs, ischemic heart diseases [IHDs], and cerebrovascular diseases [CbVDs]). In hypertensive patients, hospitalizations decreased across both sexes and emergency room (ER) visits decreased for females with increasing CoC index. Likewise, hospitalizations and medical costs related to DM decreased with increasing CoC index for both sexes. Clinic visits for DM were lowest in T3 group for both sexes. Higher CoC was associated with a lower risk of CVDs, including IHDs and CbVDs, in patients with hypertension or diabetes, as well as with all-cause mortality in patients with diabetes in the fully adjusted model. Conclusions: Continuous care for hypertension or diabetes was inversely associated with medical utilization in patients with hypertension or DM, as well as with medical costs in patients with DM. In addition, CoC decreased CVDs in patients with hypertension or diabetes and reduced all-cause mortality in patients with diabetes. Mon, 01 Jun 2026 00:00:00 GMT https://ir.ymlib.yonsei.ac.kr/handle/22282913/212116 2026-06-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/209941 Title: Associations of Elevated Red Cell Distribution Width (RDW) with Decreased Physical and Cognitive Function in Older Adults, and The Potential Mediation by Mitochondrial Energetics: The Study of Muscle, Mobility and Aging (SOMMA) Authors: Kim, Kyoung Min; Lui, Li-Yung; Mau, Theresa; Coen, Paul M.; Cummings, Steven R. Abstract: We analyzed the association between RDW and skeletal muscle mitochondrial energetics and how skeletal muscle mitochondrial energetics may mediate the associations of RDW with physical and cognitive performance. The study analyzed cross-sectional baseline data from the Study of Muscle, Mobility and Aging (SOMMA) that enrolled 864 participants aged 70 and older (mean=76.3 years). RDW, clinical and demographic parameters were assessed. Comprehensive evaluations were conducted for both physical and cognitive function using objective and subjective measures. Elevated RDW values were significantly correlated with decreased physical performance, evidenced by reduced cardiorespiratory fitness (VO2peak) and longer time to 400 m Walk, alongside impaired cognitive performance. Higher RDW values also demonstrated robust negative associations with various measurements of mitochondrial energetics, including maximal ATP production and oxidative phosphorylation. Mediation analysis revealed that impaired mitochondrial function partly mediated the associations between RDW values and VO2peak, and other physical and cognitive performance. These findings suggest that higher RDW is associated with declines in various physical and cognitive performance, with skeletal muscle mitochondrial energetics serving as a potential mediating factor. Causal inferences about potential mediation are limited by the cross-sectional design of the study. Nevertheless, the findings highlight the value of RDW as a potential biomarker for age-related declines in physical and cognitive function partly mediated by mitochondrial energetics. Fri, 01 May 2026 00:00:00 GMT https://ir.ymlib.yonsei.ac.kr/handle/22282913/209941 2026-05-01T00:00:00Z