Biology subjects

Oh, K.-S.

Publications and source records attributed to Oh, K.-S..

4 recordsLinked to original sources

bioRxiv2026

PredHLM: quantitative and interpretable prediction of metabolic half-life in human liver microsomes

MotivationHuman liver microsome (HLM)-based metabolic stability assays are fundamental in early drug discovery, shaping pharmacokinetic profiles and oral bioavailability. However, these experimental assays are labor-intensive and time-consuming, limiting their application in large-scale virtual screening. Computational models can prioritize compounds at scale, yet most are classification-based, leaving quantitative and interpretable prediction of HLM half-life limited. ResultsIn this study, we developed a quantitative machine learning model for the direct prediction of HLM half-life (T1/2) by integrating 11,790 compounds combining in-house and curated public data. Among various combinations of molecular features and learning algorithms, the XGBoost model with RDKit 2D descriptors achieved the best predictive performance, with an RMSE of 0.507 and an R2 of 0.431 on an independent test set. Shapley Additive Explanations (SHAP) analysis identified lipophilicity and known metabolic soft-spot features as the primary contributors to the predictions. These results suggest that this quantitative approach provides a practical framework for defining metabolic stability margins, thereby supporting rapid Go/No-go decisions in preclinical drug discovery. AvailabilityThe source code, data, and trained model are available at https://github.com/joshua-416/PredHLM. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/736062v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@7d94c1org.highwire.dtl.DTLVardef@b13e71org.highwire.dtl.DTLVardef@7aa684org.highwire.dtl.DTLVardef@4a2668_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

Atelocollagen exhibits superior performance compared to growth factors in upregulating proteins associated with tendon healing

PurposeWe aimed to compare the effects of atelocollagen (AC) and individual growth factors on the expression of key molecular markers associated with tendon healing. MethodsC2C12 myoblasts were cultured in Dulbeccos Modified Eagle Medium (DMEM) containing 5% fetal bovine serum (FBS) and treated with 1 nM or 10 nM of Atelocollagen (AC), bone morphogenetic protein-2 (BMP-2), transforming growth factor-beta 1 (TGF-{beta}1), insulin-like growth factor-1 (IGF-1), or vascular endothelial growth factor (VEGF) for 5 days. After 5 days of treatment, cells were harvested from the culture medium, and Western blot analysis was performed to quantify the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), Collagen type I (Col I), Collagen type III (Col III), and Tenascin C (TnC). Additionally, immunofluorescence staining was conducted to qualitatively assess cytoskeletal organization and cell adhesion, which are key factors in tendon healing. ResultsIn the AC-treated groups, the expression levels of p-ERK, Col I/Col III, and TnC were significantly higher compared to the groups treated with individual growth factors (BMP-2, IGF, VEGF, and TGF-{beta}1) (p < 0.05). These changes were dose-dependent, as there was no significant difference in protein expression between AC and the growth factors at 1 nM, whereas at 10 nM, AC treatment resulted in a significant increase (p < 0.05). In the cell proliferation assay, C2C12 myoblasts treated with AC at 10 nM exhibited significantly higher proliferation rates compared to those treated with individual growth factors (p < 0.05). Additionally, immunofluorescence analysis revealed greater cytoskeletal alignment in AC-treated cells, suggesting enhanced cell adhesion, structural organization, and mechanical stability. ConclusionsAC significantly upregulated key molecular markers involved in cell proliferation, extracellular matrix remodeling, and tendon structural integrity more effectively than individual growth factors. The increased expression of these genes in myoblasts suggests ACs potential role in promoting tendon healing. Clinical relevanceThrough the modulation of key molecular pathways critical to tendon healing, AC presents strong potential as an effective biological augmentation strategy for improving tendon-to-bone interface healing after surgical repair.

cell biology↗

bioRxiv2020

Hedgehog dysregulation contributes to tissue-specific inflammaging of resident macrophages

Age-associated low-grade sterile inflammation, commonly referred to as inflammaging, is a recognized hallmark of aging, which contributes to many age-related diseases. While tissue-resident macrophages are innate immune cells that secrete many types of inflammatory cytokines in response to various stimuli, it is not clear whether they have a role in driving inflammaging. Here we characterized the transcriptional changes associated with physiological aging in mouse resident macrophage populations across different tissues and sexes. Although the age-related transcriptomic signatures of resident macrophages were strikingly tissue-specific, the differentially expressed genes were collectively enriched for those with important innate immune functions such as antigen presentation, cytokine production, and cell adhesion. The brain-resident microglia had the most wide-ranging age-related alterations, with compromised expression of tissue-specific genes and relatively exaggerated responses to endotoxin stimulation. Despite the tissue-specific patterns of aging transcriptomes, components of the hedgehog (Hh) signaling pathway were decreased in aged macrophages across multiple tissues. In vivo suppression of Hh signaling in young animals increased the expression of pro-inflammatory cytokines, while in vitro activation of Hh signaling in old macrophages, in turn, suppressed the expression of these inflammatory cytokines. This suggests that hedgehog signaling could be a potential intervention axis for mitigating age-associated inflammation and related diseases. Overall, our data represent a resourceful catalog of tissue-specific and sex-specific transcriptomic changes in resident macrophages of peritoneum, liver, and brain, during physiological aging.

immunology↗

bioRxiv2019

IRAK1-mediated coincidence detection of microbial signals licenses inflammasome activation

The innate immune system signals through various higher order signaling complexes called supramolecular organizing centers (SMOCs), which typically organize components of a single pathway. While innate immune signaling pathways have been largely characterized using single receptor stimuli, responses to pathogens require the coordinated engagement of multiple pathways. Here, we report an IRAK1-containing SMOC formed specifically when multiple receptors are activated, which recruits select components of the TLR, MAPK and inflammasome pathways. This allows for signal flux redistribution from TLRs to inflammasomes and facilitates inflammasome licensing through an MKK7-JNK axis, which is defective in Irak1-/- mice. Furthermore, this defect in Irak1-/- mice manifests in increased susceptibility to inflammasome-sensitive pathogens and diminished IL1 production from inflammasomes after co-TLR priming. Thus, IRAK1 SMOCs form a multi-pathway coordinating hub for coincidence detection of microbial signals, which may be employed by innate immune cells as a threat assessment and thresholding mechanism for inflammasome activation.

immunology↗