https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/341 2026-07-03T22:24:46Z 2026-07-03T22:24:46Z Jang, Yong Hun Kim, Jong Min Lee, Bong Gun Hoh, Jeong-Kyu Lee, Gang Yi Kim, Hyun Ho Lyu, Ilwoo Lee, Hyun Ju https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/212943 2026-06-02T05:00:12Z 2026-05-01T00:00:00Z

Title: Long-term effects of preterm birth on cortical folding trajectories in early childhood Authors: Jang, Yong Hun; Kim, Jong Min; Lee, Bong Gun; Hoh, Jeong-Kyu; Lee, Gang Yi; Kim, Hyun Ho; Lyu, Ilwoo; Lee, Hyun Ju Abstract: Cortical folding emerges in the late prenatal period and undergoes rapid reorganization during early childhood. However, the long-term impact of folding alterations associated with preterm birth remains unclear. Herein, we analysed the structural MRI data of 56 preterm children and 206 full-term peers aged 1–7 years. We derived cortical metrics from the reconstructed cortical surfaces using a vertex-wise computation framework to characterize regional folding patterns. We then conducted a combined analysis of the local gyrification index and sulcal depth to explain folding patterns in the preterm brain. Compared with their full-term peers, preterm children exhibited a region-specific impairment pattern characterized by a significantly reduced local gyrification index and sulcal depth in the bilateral superior temporal gyrus and left superior frontal gyrus (P < 0.05). Notably, the sulcal depth in the superior temporal cortex showed significant differences between preterm and full-term children in its association with neurodevelopmental outcomes (P < 0.05), indicating an atypical structure–function relationship in preterm children. The local gyrification index was significantly reduced in the right isthmus cingulate and posterior cingulate gyri (P < 0.05), reflecting a simplified gyral configuration. The study findings suggest several folding patterns that capture diverse mechanisms of morphogenetic disruption, indicating that preterm birth induces persistent region-specific impairments in cortical folding that may affect neurodevelopmental domains. These folding-sensitive markers provide critical insights into the development of targeted interventions to optimize long-term neurodevelopmental outcomes.

2026-05-01T00:00:00Z Lee, Jeonghyeon Ryu, Ki-Young Roh, Jaesook https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/212307 2026-04-22T05:00:14Z 2026-05-01T00:00:00Z

Title: Krüppel-like factor 4 regulates extravillous trophoblast invasion and angiogenic function and is reduced in gestational diabetes mellitus Authors: Lee, Jeonghyeon; Ryu, Ki-Young; Roh, Jaesook Abstract: IntroductionPlacental extravillous trophoblasts (EVTs) are essential for decidual invasion and spiral artery remodeling, yet the transcriptional mechanisms that sustain EVT function under metabolic stress, such as gestational diabetes mellitus (GDM), remain incompletely understood, raising the possibility that metabolically responsive transcription factors such as Krüppel-like factor 4 (KLF4) may be involved.MethodsKLF4 expression and localization were examined in human placental tissues, including early second-trimester basal plates and term placentas from normoglycemic and GDM pregnancies. Functional and molecular analyses were performed in EVT-like HTR-8/SVneo cells cultured under normal or high-glucose conditions with gain- and loss-of-function modulation of KLF4. EVT migration, invasion, and angiogenic activity were assessed using wound healing, transwell, Matrigel invasion, and tube formation assays. Transcriptional regulation was evaluated by qPCR and luciferase reporter assays.ResultsKLF4 was localized to the nuclei of EVTs in second-trimester placentas, and its expression was reduced in GDM placentas. In HTR-8/SVneo cells, high-glucose exposure (15–45 mM) suppressed KLF4 expression and reduced expression of invasion- and angiogenesis-related genes, including MMP2, MMP9, VEGFA, and PGF. Exposure to 30 mM glucose impaired EVT migration, invasion, and tube formation. Restoration of KLF4 improved migratory and angiogenic capacity. Under normal glucose conditions, KLF4 overexpression selectively increased MMP9, VEGFA, and PGF expression, whereas CRISPR–Cas9–mediated KLF4 knockdown reduced expression of all four genes. Luciferase assays demonstrated selective activation of MMP9, VEGFA, and PGF promoters by KLF4.ConclusionKLF4 supports EVT invasion and angiogenic function, and its downregulation under hyperglycemic conditions may contribute to impaired placental vascular remodeling in GDM.

2026-05-01T00:00:00Z Hwang, Jae Kyoon Lim, Sung Min Kwak, Min-Jin Kim, Seung Hyun Kang, Yoongu Mustafa, Ghulam Tanpure, Rahul Sadashiv Jeon, Byong-Hun Hoh, Jeong-Kyu Park, Hyun-Kyung https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/212469 2026-04-30T06:00:24Z 2026-04-01T00:00:00Z

Title: Distinct early-life gut microbiota patterns across SGA, AGA, and LGA infants Authors: Hwang, Jae Kyoon; Lim, Sung Min; Kwak, Min-Jin; Kim, Seung Hyun; Kang, Yoongu; Mustafa, Ghulam; Tanpure, Rahul Sadashiv; Jeon, Byong-Hun; Hoh, Jeong-Kyu; Park, Hyun-Kyung Abstract: Birthweight-for-gestational-age influences neonatal physiology and health, yet its role in shaping early gut microbiome development remains insufficiently defined. Small-for-gestational-age (SGA), appropriate-for-gestational-age (AGA), and large-for-gestational-age (LGA) infants may exhibit distinct microbial maturation patterns that could influence later metabolic and developmental outcomes. We conducted a prospective cohort study and enrolled 50 late-preterm and term infants and classified them into SGA (n=18), AGA (n=20), and LGA (n=12). Serial fecal samples were collected at four postnatal time windows (0-14 and 15-80 days). 16S rRNA gene sequencing using Oxford Nanopore MinION characterized microbial composition, diversity, and community networks. Bioinformatic analyses included alpha- and beta-diversity metrics, co-occurrence network analysis, and functional pathway inference using PICRUSt2 mapped to the MetaCyc database. Clinical variables, including feeding pattern and antibiotic exposure, were assessed. Gut microbiome development differed according to birthweight categories. Microbial diversity increased with postnatal age, with SGA infants showing distinct community structures over time. Firmicutes predominated across all groups, while specific taxa exhibited group-specific patterns, including enrichment of Streptococcus spp. in LGA infants and Klebsiella spp. in SGA infants. Co-occurrence network analysis revealed a stable gut microbiota in LGA infants.Conclusion: Birthweight-for-gestational-age status was associated with distinct trajectories of early gut microbial maturation. SGA infants exhibited delayed microbial stabilization and fragmented interaction networks, whereas LGA infants demonstrated relatively early establishment of stable, Streptococcus-enriched communities. These growth-specific microbial patterns may reflect differences in early metabolic programming and highlight the potential importance of tailored microbiome-targeted strategies to optimize neonatal development. What is Known:center dot Abnormal fetal growth is associated with increased neonatal morbidity and long-term metabolic risk.center dot Early-life gut microbiota play an important role in immune and metabolic development.What is New:center dot This longitudinal study demonstrates growth-specific trajectories of early gut microbial maturation among SGA, AGA, and LGA infants born at >= 35-week gestation.center dot SGA infants exhibit delayed microbial stabilization and fragmented microbial interaction networks, whereas LGA infants show relatively earlier establishment of stable microbial communities.

2026-04-01T00:00:00Z Han, Myung-Hoon Noh, Yung-Kyun Kim, Hyunkee Kim, Kyu Shik Kim, Dong-Hoon Jung, Un Suk Lee, Kyung Suk Kwon, Mi Jung Chae, Seoung Wan Min, Kyueng-Whan https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/212780 2026-05-20T07:00:16Z 2026-04-01T00:00:00Z

Title: Multi-Omics and Machine Learning Analyses Reveal PIK3CG, PRKCD, and TRIM22 as Potential Markers of Poor Prognosis and Immune Activation in Glioblastoma Authors: Han, Myung-Hoon; Noh, Yung-Kyun; Kim, Hyunkee; Kim, Kyu Shik; Kim, Dong-Hoon; Jung, Un Suk; Lee, Kyung Suk; Kwon, Mi Jung; Chae, Seoung Wan; Min, Kyueng-Whan Abstract: Background: Glioblastoma (GBM) is one of the most aggressive brain tumors with a poor prognosis despite current treatment modalities. This study aimed to identify genes whose high expression is paradoxically associated with both poor survival and enhanced immune activity, as potential targets for combination chemotherapeutic and immunotherapeutic strategies. Methods: Transcriptomic data from patients with central nervous system World Health Organization (WHO) grade IV gliomas (based on the 2016 WHO classification) were analyzed, using datasets from The Cancer Genome Atlas (525 cases), the Chinese Glioma Genome Atlas (250 cases), and the Genotype-Tissue Expression (1,152 normal samples). We initially screened 12,041 genes, prioritizing those showing a paradoxical association with prognosis and immune activation. Key genes were selected through rank statistics, machine-learning-based survival modeling, and pathway network analysis. Further subgroup validation was performed using only isocitrate dehydrogenase (IDH)-wildtype GBM cases, in line with the 2021 WHO classification. Results: Among the 12,041 candidate genes analyzed, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), protein kinase C delta type (PRKCD), and tripartite motif-containing protein 22 (TRIM22) were identified as key biomarkers whose elevated expression was significantly associated with poorer overall and disease-specific survival in IDH-wildtype GBM. These genes also correlated with enhanced immune activity, including increased tumor-infiltrating lymphocytes and elevated expression of programmed death-ligand 1. Pathway network analysis revealed indirect associations with critical immune markers such as CD8A and CD4, suggesting potential immunomodulatory functions. Additionally, differential gene expression and disease ontology analyses demonstrated their relevance across various cancer types. Drug sensitivity profiling using the Genomics of Drug Sensitivity in Cancer database identified AGI-6780, linsitinib, and Nutlin-3a as potential therapeutic agents targeting these genes. Conclusion: This study identifies PIK3CG, PRKCD, and TRIM22 as potential biomarkers and therapeutic targets in IDH-wildtype GBM. Their paradoxical association with poor survival and immune activation may inform personalized treatment strategies that combine conventional chemotherapy with immune-based therapies. While our findings are robust across both mixed and IDH-wildtype-focused cohorts, further mechanistic validation is warranted.

2026-04-01T00:00:00Z