https://kumel.medlib.dsmc.or.kr/handle/2015.oak/29770 2026-03-19T17:50:03Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46547 Title: Biological role of cytochrome P450 family 1 subfamily A member 1 (CYP1A1) in ketogenic diet-induced modulation of lung cancer Author(s): Jaehyeon Kang; Dong Soo Seo; Yusra Ahmad; Sungjun Park; Jeongwoo Yoo; Junhyeok Lee; Seungwoo Baek; Sungmin Joo; Huiyoung Kwon; Ho Jung Bae; Heedoo Lee; Taeg Kyu Kwon; Younghoon Jang Abstract: Cancer is a metabolic disease influenced by diet, diet-related nutrients, the tumor microenvironment, and metabolic signaling, all of which can significantly affect cancer progression. Although ketogenic diet (KD) has gained attention for its potential therapeutic effects in cancer, the relationship between KD, cancer biology, and metabolic signaling remains underexplored. In this study, we aimed to investigate the effect of KD on lung cancer biology using an in vivo model developed with AAV and CRISPR-Cas9 knock-in mice fed either a KD or high-carbohydrate diet (HCD). RNA-seq analysis revealed that KD markedly upregulated expression of Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) in lung cancer tissues compared to HCD. Protein analysis confirmed increased CYP1A1 levels under KD independently of aryl hydrocarbon receptor (AhR) protein levels. Similarly, in A549 and H460 human lung cancer cells treated with β-hydroxybutyrate and low-glucose conditions mimicking KD, CYP1A1 expression was also elevated. Interestingly, we observed that CYP1A1 expression is dependent on AhR activity and nuclear translocation in A549 cells in vitro. Transcriptome analysis of CYP1A1 knockdown A549 cells indicated that CYP1A1 is crucial for regulating cell cycle genes, including cyclin D. These findings highlight the biological significance of CYP1A1 in KD-induced changes in lung cancer, suggesting its role in cell proliferation and tumor development. This study also provides insights into the metabolic signaling underlying the effects of KD on cancer, offering potential directions for future therapeutic strategies. 2024-12-31T15:00:00Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46519 Title: Design of cathepsin-sensitive linkers for tumor-selective bioconjugate drug delivery Author(s): Anil Giri; Yulim Shin; Jin Ha; Siyeon Chae; Prabhat Shrestha; Khang-Yen Pham; Taeg Kyu Kwon; Jong Ho Park; Jee-Heon Jeong; Na Kyeong Lee; Simmyung Yook Abstract: Cysteine cathepsin, particularly cathepsin B, have emerged as pivotal enzymatic targets in the design of drug delivery systems owing to their overexpression in diverse pathological conditions, most notably cancer. This review provides a comprehensive overview of cathepsin B-cleavable linkers, emphasizing their role in current bioconjugate design and their application across multiple therapeutic platforms. It also provides a comparative overview of linker engineering guided by cathepsin B, ranging from simple dipeptides constructs to modified peptide linkers. These structural refinements are correlated with improvements in substrate discrimination, stability, and cleavage efficiency. Substantial attention is provided to three primary bioconjugate platforms: antibody-drug conjugates (ADCs), prodrug systems and nanoparticle conjugates. Each section enumerates the corresponding unique design, conjugation chemistry, payload distribution modalities, and progress in regulatory translation. The parallel evaluation supports that, while collectively successful, ADCs have yielded the most mature clinical outcomes, notwithstanding ongoing refinements that promise to widen the therapeutic index of prodrug and nanoparticle platforms. Key challenges include achieving a balance between linker stability in circulation and efficient cleavage at the target site, minimizing off-target activation, and accounting for variability in cathepsin expression among patients. Future direction focusses on both advancing linker technology through enhanced stability, refined pharmacokinetics, and multi-mechanism combination strategies and implementing patient stratification for clinical relevance. 2024-12-31T15:00:00Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46490 Title: In vivo analyses of embryotoxicity and teratogenicity of gold nanoparticles: Emphasis on the surface chemistry and toxicological responses Author(s): Tayaba Ismail; Yong-Gyu Jeong; Hyun-Kyung Lee; Hongchan Lee; Youni Kim; Jun-Yeong Lee; Sang-Hyun Kim; Hong-Yeoul Ryu; Taeg Kyu Kwon; Tae Joo Park; Taejoon Kwon; Dongwoo Khang; Hyun-Shik Lee Abstract: The surface chemistry and physical characteristics of gold nanoparticles (AuNPs) influence their biological interactions and toxicological responses. However, the toxicological effects of surface charge on embryonic development remain poorly understood. In this study, we investigated the in vivo developmental toxicity and teratogenicity of differentially charged AuNPs during early embryogenesis of Xenopus laevis – a sensitive and ecologically relevant animal model for developmental toxicology. Our study indicated that cationic AuNPs induced significant embryotoxicity and teratogenicity including lethality, phenotypical abnormalities and disruption of gene expression associated with liver, digestive tract, neural, and eye development. In contrast, such effects, including lethality and malformations associated with changes in gene expression were not observed in embryos exposed to anionic AuNPs. In addition, cationic AuNPs affected ciliogenesis by reducing the number of multiciliated cells and disturbing cilia-driven fluid flow, a critical endpoint in nanoparticle-induced toxicity. Furthermore, gene expression profiles suggested that necroptosis might be the mechanism of cell death in embryos exposed to cationic AuNPs. Notably, the surface charge dependent AuNPs exposure leading to impaired ciliogenesis and activation of necroptosis during embryogenesis represents significant endpoints in nanotoxicology. Unlike previous studies focusing on zebrafish or rodents, this study provides the first systematic evaluation in X. laevis embryos with identical nanoparticle cores but distinct surface chemistries. Our study underscores the significance of nanoparticle surface functionalization in determining developmental toxicity and pinpoints the ecological risks imposed by cationic AuNPs during early embryonic development in aquatic 2024-12-31T15:00:00Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46453 Title: Placental Transcriptomic Analysis in Retinopathy of Prematurity Reactivation After Anti-VEGF Treatment Author(s): Junho Kang; Shin Kim; Jin Gon Bae; Ji Hye Jang Abstract: Purpose: This study aimed to identify differentially expressed fetal factors in infants with reactivation of retinopathy of prematurity (ROP) using placental transcriptome analysis. Design: This retrospective case series analyzed placental transcriptome differences between preterm infants with and without reactivation of ROP following anti-vascular endothelial growth factor (VEGF) treatment. Methods: We enrolled preterm infants who initially received 0.2 mg of ranibizumab for the treatment of ROP and whose maternal placentas were stored at Human Resources Bank. RNA sequencing was performed to identify differentially expressed genes (DEGs) between reactivated ROP (n = 4) and control (n = 8) groups. Bioinformatics analyses included functional enrichment, protein-protein interaction network construction, and hub gene identification. To evaluate predictive potential for ROP reactivation, genes with an ROC curve ≥ 0.7 were considered. Results: A total of 329 DEGs were identified in the reactivated ROP group, comprising 207 upregulated and 122 downregulated genes. Among them, 15 hub genes, all upregulated, were related to VEGFA-VEGF receptor 2 signaling and trophoblast cell surface antigen 2 regulatory signaling. Of these, 9 hub genes (ACTG1, BSG, ETS1, FN1, FOXO4, IGFBP3, NUMB, MDM2, and SMARCA2) showed an AUC > 0.7, indicating high predictive potential. Except for FOXO4 and SMARCA2, the remaining 7 were associated with angiogenesis, including the VEGF pathway and endothelial cell activity. Conclusions: Upregulation of genes involved in the VEGFA-VEGF receptor 2 signaling pathway was significantly identified in the maternal placentas of infants with reactivated ROP. These 9 hub genes may serve as potential biomarkers for predicting ROP reactivation following anti-VEGF therapy. 2024-12-31T15:00:00Z