Biomedical subjects

Daisuke Okuzaki

Publications and source records attributed to Daisuke Okuzaki.

3 recordsLinked to original sources

PubMed2026

Admission whole-blood transcriptomic characterization of a neutrophil-predominant systemic immune response in patients with acute traumatic brain injury.

BACKGROUND: Acute traumatic brain injury (TBI) is accompanied by systemic immune responses, but their whole-blood transcriptomic features at hospital arrival remain incompletely characterized. We aimed to characterize these features in patients with acute TBI compared with healthy controls. METHODS: In this single-center prospective observational study, we performed whole-blood RNA sequencing on hospital-arrival samples from 42 patients with acute TBI and 21 healthy controls. Analyses included differential expression (limma-voom; FDR < 0.05, |log2FC| > 0.7), functional enrichment, Ingenuity Pathway Analysis, CIBERSORTx LM22 deconvolution, and per-sample neutrophil degranulation signature scoring. RESULTS: Differential expression analysis identified 996 upregulated and 863 downregulated genes, with marked upregulation of inflammation-, innate immunity-, and neutrophil-related genes including DUSP1, HMGB2, MMP9, and S100A8. Canonical pathways with positive IPA z-scores included Neutrophil degranulation, Neutrophil Extracellular Trap Signaling Pathway, and Toll-like Receptor Signaling; upstream regulators included TNF, IL1B, IFNG, and STAT3. Deconvolution identified 7 of 22 differing subsets (q < 0.05), with relatively higher myeloid and lower lymphoid fractions in TBI. The Neutrophil degranulation signature score correlated with Injury Severity Score within TBI (Spearman ρ = +0.55; q < 0.001). CONCLUSIONS: Admission whole-blood transcriptomics characterized a neutrophil-predominant systemic transcriptional response in patients with acute TBI. This response was also evident among patients without major extracranial injury and was associated with total ISS. However, because the study lacked an appropriately matched non-TBI trauma comparator, the findings should be interpreted as a descriptive characterization of a systemic injury response accompanying TBI and do not establish a TBI-specific molecular signature or mechanism.

gene expression↗

PubMed2026

Evaluation of methacrylic resin-modified calcium silicate cements for pulpal healing using an experimental pulpitis model.

Recently, vital pulp treatment (VPT), including direct pulp capping, which preserves pulp vitality and extends the functional lifespan of teeth, has garnered significant attention. The purpose of this study was to evaluate the performance of calcium silicate cement, the gold standard for VPT, alongside hydraulic calcium silicate cement (Pro-MTA), a material with extensive evidence of effectiveness, Bis-GMA resin-modified calcium silicate cement (TH), and a newly developed material, methacrylate resin-modified calcium silicate cement (RM-MTA), in a model of pulpitis induced by caries progression. Additionally, the calcium ion (Ca2+) release capacity of these materials and their comprehensive effects on pulpal wound healing were assessed using RNA sequencing (RNA-seq). In both sound pulp models and caries-induced pulpitis models, RM-MTA and Pro-MTA exhibited similar performances. Unlike TH, they induced significant tertiary dentin formation within the dental pulp beneath the material, without any residual inflammatory cells. Inflammation was specifically assessed with a focus on M1/M2 macrophages. While the timing of Ca2+ ion release differed among the materials, the total amount released was comparable, although the release of calcium ions (Ca2+) from TH was significantly lower compared to that observed for the above materials. Moreover, comprehensive genetic analysis revealed that the expression of cell proliferation-related genes was selectively reduced in TH, suggesting that differences in resin composition may account for these variations in behavior. These findings suggest that RM-MTA induces tertiary dentin and demonstrates biocompatibility comparable to that of Pro-MTA. This makes it suitable for the treatment of both sound and mildly inflamed pulp tissues. Additionally, its resin properties are expected to enhance both mechanical performance and clinical handling.

Journal Article↗

PubMed2025

CAR NK cell production from human cord blood NK progenitor cells is enhanced by stimulation of the IL-15 receptor.

Cord blood (CB)-derived chimeric antigen receptor (CAR) natural killer (NK) cells have demonstrated significant antitumor efficacy. We recently reported that CB-derived CAR NK cells predominantly originate from CD7+CD56-CD34-HLA-DR-Lin- NK cell precursors in CB. Here, we demonstrate that stimulating the interleukin (IL)-15 receptor on these NK precursors enhances the production of CAR NK cells from CB cells. In CB CD56-CD34-HLA-DR-Lin- cells, the IL-15 receptor was exclusively expressed on CD7+ NK cell precursors. Using K562 feeder cells that express not only 4-1BB ligand and membrane-bound (mb) IL-21 but also mbIL-15 significantly increased the production of mature NK cells from the purified NK cell precursors or T cell-depleted CB cells. The in vitro and in vivo antitumor effects of CAR NK cells generated using K562 feeder cells that express mbIL-15 were comparable to those of CAR NK cells produced using K562 feeder cells that do not express mbIL-15. These results suggest that K562 feeder cells expressing 4-1BBL, mbIL-21, and mbIL-15 can increase the production of CAR NK cells from CB cells while maintaining their cytotoxic potential. This method could also be useful for expanding NK cells from CB for any type of adoptive NK cell therapy with or without CAR transduction.

Humans↗