Kyung Hoon Sun

Purpose: Go6976 is a staurosporine-derived kinase inhibitor that interferes with checkpoint signaling pathways. Although Go6976 has been widely used as a pharmacological inhibitor, its effects on embryonic stem cell maintenance and survival remain unclear. This study investigated the effects of Go6976 on pluripotency, differentiation, and apoptosis in mouse embryonic stem cells (mESCs).Methods: mESCs were treated with Go6976 under leukemia inhibitory factor (LIF)-supplemented conditions. Pluripotency was assessed by alkaline phosphatase (AP) staining and analysis of pluripotency marker expression. Differentiation was evaluated by measuring lineage-specific gene expression. Apoptosis was analyzed by cell cycle profiling and Annexin V staining. To clarify whether the effects of Go6976 were associated with protein kinase C inhibition, its effects were compared with those of the protein kinase C inhibitor GF109203X. In vitro kinase assays were also performed to evaluate checkpoint kinase 1 (Chk1) activity. All experiments were performed independently at least 3 times, and statistical significance was determined using one-way analysis of variance, as appropriate.Results: Go6976 significantly reduced AP-positive colonies despite the presence of LIF and decreased the expression of pluripotency markers, including Oct4 and Sox2. In contrast, Go6976 increased the expression of differentiation markers, including Brachyury and FGF5.Conclusion: Pharmacological inhibition of Chk1 by Go6976 promoted differentiation and apoptosis in mESCs. These findings support a role for Chk1-associated signaling in stem cell homeostasis and suggest its potential relevance to developmental toxicology.

Background: Mastoid obliteration following canal wall down mastoidectomy reduces cavity-related morbidity. Conventional obliteration materials act primarily as passive fillers, whereas tissue engineering (TE) strategies aim to achieve biologically active bone regeneration. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library were searched from January 2010 to December 2025. Studies evaluating tissue engineering-assisted mastoid obliteration involving growth factors, mesenchymal stem cells, polymer scaffolds, or 3D-printed constructs were included. Results: Fifteen studies met inclusion criteria (12 preclinical and three clinical). Polymer-supported MSC constructs demonstrated the most consistent osteogenic enhancement in animal models. Clinical evidence remains limited to small PRP-based case series. Conclusions: Preliminary evidence suggests that tissue engineering-assisted mastoid obliteration has regenerative potential, although the evidence is limited by predominantly preclinical data and a moderate-to-high risk of bias. Standardized outcome measures and well-designed prospective clinical studies are required to confirm long-term safety and efficacy.

Canal wall down mastoidectomy (CWD) effectively eradicates cholesteatoma and chronic otitis media but frequently results in a problematic open mastoid cavity. Mastoid obliteration aims to reduce cavity-related morbidity. Bioceramic materials, including hydroxyapatite (HA), tricalcium phosphate (TCP), and bioactive glass (BAG), have been increasingly adopted because of their osteoconductive, biocompatible, and antimicrobial properties. This systematic review evaluates the clinical outcomes and complications of bioceramic mastoid obliteration following CWD. A systematic literature search of PubMed, Scopus, and Web of Science was conducted for studies published between 2005 and 2025, following PRISMA guidelines. Clinical studies reporting outcomes of bioceramic mastoid obliteration after CWD were included. Thirteen clinical studies were included. HA-, TCP-, and BAG-based materials demonstrated high obliteration success rates (>90% in most series). BAG S53P4 was consistently associated with low infection rates and favorable epithelialization, whereas earlier HA cement formulations were occasionally associated with revision-requiring complications. Bioceramic scaffolds represent safe and effective materials for mastoid obliteration after CWD. BAG offers additional antibacterial advantages, while HA provides predictable volume stability. Further prospective and comparative studies are required to establish material superiority and long-term outcomes.

Background: Hyperbaric oxygen therapy (HBOT) is the standard treatment for moderate to severe carbon monoxide (CO) poisoning, but middle ear barotrauma (MEB) remains a common complication. This study identified risk factors associated with MEB in patients undergoing monoplace HBOT. Methods: This retrospective cohort study included patients treated for CO poisoning with monoplace HBOT at a tertiary academic hospital between May 2021 and December 2023. MEB severity was assessed before and after treatment using video otoscopy and graded according to the modified O’Neill Grading System. Results: MEB occurred predominantly at lower severity grades according to the O’Neill scale. In univariate analysis, significant risk factors for MEB included altered mental status at presentation (OR: 3.16, 95% CI: 1.35–7.40, p = 0.008), serum albumin > 4.3 g/dL (OR: 0.22, 95% CI: 0.10–0.65, p = 0.004), and magnesium levels (OR: 0.21, 95% CI: 0.05–0.98, p = 0.046). Multivariate analysis confirmed altered mental status (OR: 3.16, 95% CI: 1.05–9.52, p = 0.041), albumin > 4.3 g/dL (OR: 0.26, 95% CI: 0.10–0.65, p = 0.004), and magnesium level (OR: 0.21, 95% CI: 0.05–0.88, p = 0.033) as independent predictors of MEB. Patients with higher albumin and magnesium levels showed lower risk. Conclusions: Altered mental status, lower albumin, and lower magnesium levels predicted middle ear barotrauma in patients undergoing monoplace HBOT for CO poisoning. These findings highlight the importance of careful pre-treatment evaluation and close monitoring during therapy to reduce the incidence of MEB.

Background/Objectives: The regeneration of the facial nerve using low-level laser therapy (LLLT) has been infrequently reported. Polydeoxyribonucleotides (PDRNs), a blend of short deoxyribonucleotide polymers known for their non-toxic and non-allergic properties, are recognized as a stimulator of cell growth that enhances cell proliferation and supports wound healing. This study investigates the synergistic effect of the topical sustained release of PDRN/F-127 and LLLT on facial nerve regeneration following crush injury-induced paralysis in rats. Methods: The main trunk of the facial nerve was compressed for 1 min using a hemostat. Animals were divided into five groups: a control group (n = 4), group I (Pluronic F-127 only, n = 4), group II (Pluronic F-127/PDRN, n = 4), group III (Pluronic F-127 + LLLT, n = 4), and group IV (Pluronic F-127/PDRN + LLLT, n = 4). We measured the recovery of vibrissa fibrillation, action potential, and facial nerve blood flow (FNBF). Results: Group IV exhibited a comparatively faster development of vibrissa fibrillation over time than the other groups. After the intervention, significant differences in vibrissa fibrillation values were observed at all time points (p = 0.0028) according to the repeated one-way ANOVA. Regarding the threshold of action potential, all five groups revealed a significant difference (one-way ANOVA, p < 0.0001; multiple comparisons via Tukey’s test). Among the groups, group IV showed a significantly reduced threshold of action potential compared to the other groups. Group IV showed the most notable recovery in FNBF compared to the other groups. One-way ANOVA showed a significant difference (p < 0.0001; multiple comparisons by Dunnett’s test). Conclusions: These findings suggest that PDRN and LLLT may work together synergistically to enhance peripheral nerve regeneration. Future studies should investigate the underlying molecular mechanisms and evaluate the potential clinical applications of this combined treatment strategy.

Lee YS, et al. Yonsei Med J. 2025 Jan;66:e16. https://doi.org/10.3349/ymj.2024.0068

Background: Platelet-to-Lymphocyte ratio (PLR) has been studied as a prognostic factor for various diseases and traumas. This study examined the utility of PLR as a tool for predicting 30-day mortality in patients experiencing severe trauma.Methods: This study included 139 patients who experienced trauma and fulfilled ≥1 criteria for activation of the hospital’s severe trauma team. Patients were divided into non-survivor and survivor groups. Mean PLR values were compared between the groups, the optimal PLR cut-off value was determined, and mortality and survival analyses were performed. Statistical analyses were performed using SPSS ver. 26.0. The threshold of statistical significance was P<0.05.Results: There was a significant difference in mean (±standard deviation) PLR between the non-survivor (n=36) and survivor (n=103) groups (53.4±30.1 vs. 89.9±53.3, respectively; P<0.001). Receiver operating characteristic (ROC) curve analysis revealed an optimal PLR cut-off of 65.35 (sensitivity, 0.621; specificity, 0.694, respectively; area under the ROC curve, 0.742), and Kaplan-Meier survival analysis revealed a significant difference in mortality rate between the two groups.Conclusions: PLR can be calculated quickly and easily from a routine complete blood count, which is often performed in the emergency department for individuals who experience trauma. The PLR is useful for predicting 30-day mortality in trauma patients with severe trauma team activation.

Sung Min Lee, Kyung Hoon Sun. Med Biol Sci Eng 2024;7:64-7. https://doi.org/10.30579/mbse.2024.7.1.64

This study investigated the effects of silibinin, derived from milk thistle (Silybum marianum), on lipopolysaccharide (LPS)-induced morphological changes in mouse macrophages. Silibinin was treated at various doses and time points to assess its effects on macrophage activation, including morphological changes and phagocytosis. Silibinin effectively inhibited LPS-induced pseudopodia formation and size increase, while unstimulated cells remained round. Silibinin’s impact on phagocytosis was dose- and time-dependent, showing a decrease. We explored its mechanism of action on kinases using a MAPK array. Among the three MAPK family members tested, silibinin had a limited effect on JNK and p38 but significantly inhibited ERK1/2 and related RSK1/2. Silibinin also inhibited MKK6, AKT3, MSK2, p70S6K, and GSK-3β. These findings highlight silibinin’s potent inhibitory effects on phagocytosis and morphological changes in macrophages. We suggest its potential as an anti-inflammatory agent due to its ability to target key inflammatory pathways involving ERK1/2 and related kinases. Overall, this study demonstrates the promising therapeutic properties of silibinin in modulating macrophage function and inflammation.

The impact of metformin on the rat facial nerve following crush injury has only occasionally been documented to date. The purpose of the current investigation was to use functional and electrophysiological evaluations to investigate the effects of metformin administration on recovery following crush injury to the rat facial nerve. The rats were randomly divided into four groups: the nonDM/PBS group (n = 4), the nonDM/metformin group (n = 4), the DM/PBS group (n = 4), and the DM/metformin group (n = 4). Diabetes was generated by an intraperitoneal injection of streptozotocin. Facial nerve paralysis was induced by a crush injury 7 days after diabetes induction. The blood glucose levels of the DM/PBS and DM/metformin groups were maintained at over 300 mg/dL, whereas the blood glucose levels of the nonDM/PBS and nonDM/metformin groups were maintained at less than 150 mg/dL. There was no significant difference between the two nonDM groups. In comparison to the PBS group, the metformin group’s recurrence of vibrissa fibrillation occurred noticeably sooner over time. The nonDM/metformin group showed the highest recovery rate in the second, third, and fourth weeks post-crush, respectively. The threshold of action potential 4 weeks after crush injury showed that the nonDM/metformin group had a significantly lower mean threshold of MAP compared to other groups. The short-term effect of metformin on the recovery of facial nerve blood flow (FNBF) was significantly increased compared to the DM/PBS group. However, there was no significant difference in FNBF between the nonDM/metformin and nonDM/PBS groups. A diabetic condition promoted a delay in FN regeneration. Metformin is able to accelerate functional recovery in diabetic or nondiabetic FN-injured rats. Further studies using a morphometric or molecular approach are planned to understand the pharmacologic mechanism of metformin.