https://ir.ymlib.yonsei.ac.kr/handle/22282913/168844 2026-04-20T03:17:44Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211761 Title: A transferable SARS-CoV-2 IRES module enables dual translation initiation for enhanced antigen expression in COVID-19 mRNA vaccines Authors: Seo, Han Young; Jung, Haewon; Lee, Se-Young; Jung, Hae-Gwang; Son, Yu-Min; Bak, Yeonju; Hwang, Seo-Yeon; Kim, Jung-Hee; Park, In Ho; Shin, Jeon-Soo; Oh, Jong-Won Abstract: mRNA vaccines are a versatile platform for infectious disease prevention and therapeutic applications, yet their performance is limited by exclusive reliance on cap-dependent translation, which is markedly suppressed under hypoxia and cellular stress. Here, we report a hybrid 5 ' untranslated region (5 ' UTR) that enables dual translation initiation via both cap-dependent and internal ribosome entry site (IRES) mechanisms. This element integrates a minimal stem-loop 4.5-5 module (SL4.5-5) from the SARS-CoV-2 genomic 5 ' UTR, in which a conserved 5 '-UUUCGU-3 ' motif within the SL5 loops is essential for function. Incorporating the SL4.5-5 module downstream of conventional 5 ' UTRs confers cap-independent translation capacity and enhances overall translation efficiency under translation-restrictive conditions such as hypoxia. When applied to the 5 ' UTRs of clinically validated COVID-19 vaccines, this module improves antigen expression in both modified and unmodified mRNAs. Notably, unmodified Omicron BA.5 and XBB.1.5 mRNA vaccines containing this element elicited potent humoral and cellular immune responses at sub-microgram doses, comparable to those induced by the approved N1-methylpseu-douridine-incorporated mRNA vaccine, raxtozinameran. These findings identify SL4.5-5 as a modular IRES element that enables dual translation initiation, promoting efficient protein synthesis under cap-dependent translation-restrictive conditions and expanding the functional landscape of mRNA vaccines and therapeutics beyond cap-dependent limitations. 2026-06-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211184 Title: Distinct serum metabolic profiles with supportive diagnostic value in differentiating tuberculosis and Mycobacterium avium complex pulmonary disease Authors: Kim, Keu Eun San; Lee, Ye Jin; Park, Ji Hae; Kwak, Nakwon; Kim, Su-Young; Jhun, Byung Woo; Yim, Jae-Joon; Shin, Sung Jae; 박지해 Abstract: Background: Pulmonary infectious diseases caused by Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium avium complex (MAC), remain significant public health threats. However, current gold-standard diagnostics are time-consuming and have limited ability to differentiate these clinically similar presentations. This study investigated serum metabolic distinctions between tuberculosis (TB) and MAC pulmonary disease (MAC-PD) to identify biomarkers with supportive diagnostic value for differential diagnosis. Methods: We performed LC/MS-based metabolic profiling of 181 serum samples from TB and MAC-PD patients. The study cohort was subsequently divided into a training set (TB, n = 30; MAC-PD, n = 30) and a validation set (TB, n = 51; MAC-PD, n = 70). Results: Five key metabolites were identified, including four sphingoid base lipids that were decreased in TB compared with MAC-PD, and 2-hydroxyglutaric acid (2-HG), which was increased. Logistic regression using this five-metabolite panel achieved strong discriminatory performance, with an area under the curve of 0.988 (95 % CI: 0.970-1.00 0) in the training set and 0.997 (95 % CI: 0.991-1.00 0) in the validation set. Consistent performance across multiple machine learning models reinforces the stability and supportive diagnostic value of the five-metabolite panel. Conclusions: This study provides a novel approach for the differential diagnosis of two major mycobacterial pulmonary diseases. The identified metabolites, particularly alterations in sphingoid base lipids and 2-HG, demonstrated robust discriminative potential. These findings support their potential role as biomarkers in clinical practice, enabling earlier and more accurate differentiation of TB and MAC-PD. (c) 2026 The Author(s). Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 2026-04-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211424 Title: Patient-Derived Organoids from Multiple Sites of a Single Tumor Recapitulates Intratumoral Heterogeneity in Patients with Gastric Cancer Authors: Yoon, Bo Kyung; Bae, Yoojin; Je, Yeonjin; Joo, Seyeon; Kim, Yuna; Shin, Su-Jin; Fang, Sungsoon; Kim, Jie-Hyun; 윤보경 Abstract: Background/Aims: Patient-derived organoids (PDOs) are promising preclinical models that replicate critical tumor features. However, intratumoral heterogeneity challenges the clinical utility of PDOs, especially in capturing diverse tumor cell subpopulations. Methods: Single-cell transcriptomics was used to analyze PDOs from distinct sites within a single gastric cancer tumor, aiming to assess their ability to reflect intratumoral heterogeneity. Results: The PDOs displayed similarities in gene expression but also exhibited distinct profiles. Single-cell analysis of PDOs revealed upregulation of markers for neuroendocrine tumors, which was validated via immunohistochemistry staining of neuron-specific enolase in the primary tumor. Notably, heat shock proteins showed significant variability among the PDOs, impacting immune responses. Tumors with abundant heat shock proteins are reported to have increased cytotoxic T cell activity. Conclusions: Intratumoral heterogeneity poses challenges for PDO-based models, highlighting the need for comprehensive assessment. Despite their limitations, PDOs offer valuable insights into precision medicine for patients with gastric cancer, aiding in the development of therapeutic strategies. (Gut Liver, Published online September 5, 2025) 2026-03-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211792 Title: Kasugamycin Inhibits Melanoma Lung Metastasis and CHI3L1-Driven M2-Like Tumor-Associated Macrophage Differentiation Authors: Sadanaga, Takayuki; Jeong, Han-Seok; Cortez, Roberto; Lee, Joyce H.; Kamle, Suchitra; Ma, Bing; Shin, Sung Jae; Elias, Jack A.; Lee, Chun Geun Abstract: Purpose: Chitinase-3-like-1 (CHI3L1) is a potent immune modulator implicated in tumor progression and immune suppression, including melanoma lung metastasis. Kasugamycin (KSM) has been reported as a pan-chitinase inhibitor with antifibrotic activity, but its effects on CHI3L1-driven immune regulation remain poorly defined. This study aimed to determine whether KSM suppresses CHI3L1-mediated tumor progression by modulating tumor-associated macrophage (TAM) differentiation and to elucidate the underlying molecular mechanisms. Methods: The anti-tumor effects of KSM were evaluated using a B16/F10 melanoma lung metastasis model. CHI3L1 gain-of-function approaches were used to assess specificity. Lung immune populations were analyzed by flow cytometry. Human THP-1 monocytes were used to examine CHI3L1-induced macrophage differentiation in vitro. Bulk RNA sequencing was performed on differentiated macrophages to identify downstream signaling pathways. Pharmacologic inhibition studies were conducted using the epidermal growth factor receptor (EGFR) inhibitor gefitinib to validate mechanistic links. Results: KSM treatment significantly reduced melanoma lung metastasis in a dose-dependent manner. CHI3L1 overexpression enhanced melanoma lung colony formation, which was effectively abrogated by KSM, indicating CHI3L1-specific anti-tumor activity. In melanoma-challenged lungs, KSM markedly decreased M2-like macrophages expressing CD206, CD163, and PD-L1. In vitro, CHI3L1 promoted M2 macrophage differentiation in THP-1 cells, which was strongly suppressed by KSM. Transcriptomic analysis revealed that EGFR expression was robustly induced by CHI3L1 and counter-regulated by KSM. Inhibition of EGFR signaling with gefitinib significantly attenuated CHI3L1-driven STAT3 activation and M2 macrophage polarization. Conclusion: These findings identify a previously unrecognized anti-tumor mechanism of KSM through inhibition of CHI3L1-EGFR-STAT3 signaling and suppression of M2-like TAM differentiation. KSM may therefore represent a promising immunomodulatory strategy for treating melanoma lung metastasis and other CHI3L1-driven malignancies. 2026-03-01T00:00:00Z