Diabetic nephropathy (DN) is among the most serious diabetes-related microvascular complications, a disease with risks leading to end-stage kidney disease (ESKD). However, only limited DN treatment options are currently available. DN development and progression involve different pathological mechanisms, including inflammation and oxidative stress. Stachybotrys microspora is a fungus producing the triphenyl phenol SMTP-44D, which exhibits anti-inflammatory and antioxidant properties in several disease models. In this study, we aimed to evaluate the effects of SMTP-44D in a DN mouse model, which was created by removing the right kidney of 6-week-old db/db mice. We administered SMTP-44D for 10 weeks between weeks 6 and 16 of age to observe blood glucose levels, renal function parameters, inflammatory factors, oxidative stress markers, and histopathological characteristics. SMTP-44D treatment did not reduce blood glucose level but significantly decreased serum creatinine and urinary albumin as renal function parameters, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and nicotinamide adenine dinucleotide phosphate oxidase-1 as inflammation and oxidative stress in the kidney. In addition, histopathological assessment revealed its preventive effect against glomerulosclerosis and local regenerative tubule. Therefore, we discovered that SMTP-44D might protect renal function without affecting blood glucose level in DN possibly via suppression of inflammation and oxidative stress. In conclusion, SMTP-44D could be a potential DN treatment agent, even in patients with poor glycemic control.

Immune checkpoint inhibitors (ICIs), essential in cancer therapy, can cause severe immune-related adverse events (irAEs), including myocarditis with a high fatality rate. Currently, the pathogenesis, biomarkers, and risk factors of ICI-induced myocarditis (ICIM) are not fully understood. This exploratory study aimed to develop machine learning-based models to predict the onset of ICIM within 3 months of starting ICI therapy, using a large health insurance database. The models were constructed using the Light Gradient Boosting Machine (LightGBM) and Random Forest algorithms, incorporating clinical variables such as comorbidities and prior medication classifications. In this study, a strategy combining undersampling and bagging was used to minimize the impact of highly imbalanced datasets. The Random Forest model demonstrated superior performance compared with the LightGBM model, and the SHapley Additive exPlanations (SHAP) analysis for the Random Forest model revealed that the concurrent use of ICIs was the most important variable for predictions. Although predictive performance remains limited (AUROC ≈ 0.63), this exploratory framework demonstrates the feasibility of developing data-driven risk prediction models for ICIM. Future studies with expanded datasets and integration of laboratory parameters are warranted to improve predictive accuracy and potential clinical applicability.

Three-dimensional (3D) hepatocyte spheroid cultures offer an advanced in vitro model for investigating liver function and drug metabolism; however, oxygen diffusion limitations restrict spheroid size and functionality. In the present study, we developed a 3D spheroid culture system using HepaRG, a human hepatoma-derived cell line that retains drug-metabolizing enzymes, and oxygen-permeable plates composed of 4-polymethyl-1-pentene (PMP) to improve oxygen availability and metabolic performance. Morphological analysis showed enhanced spheroid circularity and compactness in the PMP culture, implying enhanced cell–cell adhesion. Hypoxic imaging revealed that PMP plate-based cultures markedly reduced central hypoxia, enabling the formation of spheroids with up to 20000 cells. Using clozapine, a low-clearance antipsychotic drug with limited metabolic elimination that is metabolized by monooxygenases, including CYP3A4 and flavin-containing monooxygenase (FMO), we observed an enhanced decline in clozapine levels in PMP plates compared with the clozapine levels seen in the conventional polystyrene plates. Furthermore, the mRNA and protein-expression levels of CYP3A4 and FMO3 were upregulated in the spheroids cultured on PMP plates. These results suggest that improved oxygenation enhances hepatic functionality in 3D cultures by maintaining cell viability and promoting the expression of drug-metabolizing enzymes. Therefore, the PMP plate-based spheroid model offers a practical and physiologically relevant platform for investigating drug metabolism and hepatotoxicity.

We investigated the impact of operating room pharmacists on the appropriate use of antimicrobial prophylaxis (AMP) in otorhinolaryngology-head and neck surgery. Patients without intervention by operating room pharmacists (April 1, 2017, to March 31, 2019) and those who underwent intervention by operating room pharmacists (October 1, 2019, to March 31, 2021) were compared. Additionally, an interrupted time-series (ITS) analysis was conducted as a sensitivity analysis to assess temporal trends. Overall, 1697 patients (999 in the non-intervention group and 698 in the intervention group) were included, and 213 matched pairs were analyzed after 1 : 1 propensity score matching. The compliance rate of AMP administered within 1 h prior to incision was significantly higher in the intervention group than in the non-intervention group (98.1 vs. 93.4%; p = 0.027). In the subgroup analysis, the compliance rate of the guideline-recommended initial dose in patients weighing ≥80 kg was significantly higher in the intervention group than in the non-intervention group (93.1 vs. 70.7%; p < 0.001). The compliance rate of additional doses administered at the guideline-recommended intervals in patients with an estimated glomerular filtration rate individualized body surface area (eGFR_ind) <50 mL/min was significantly higher in the intervention group than in the non-intervention group (89.8 vs. 80.4%; p = 0.041). ITS analysis showed that the improvement trend in AMP compliance stabilized after the intervention, indicating sustained intraoperative management. No significant differences were observed in the postoperative or total hospital stay between the two groups. In conclusion, interventions by operating room pharmacists significantly improved the appropriate use of intraoperative AMP.

Neuroinflammation contributes to the pathogenesis of various central nervous system disorders. TPNA10168, a novel nuclear factor erythroid 2-related factor 2 activator, exhibits neuroprotective effects in vitro and in vivo and anti-inflammatory activity in vitro. In this study, we examined the in vivo efficacy of TPNA10168 in a mouse model of systemic inflammation established by lipopolysaccharide (LPS) treatment. TPNA10168 attenuated the LPS-induced expression of several proinflammatory cytokines, such as tumor necrosis factor-α in the liver and interleukin-1β in the brain, and upregulated heme oxygenase-1 in both tissues. Although it did not suppress microglial activation in the brain, TPNA10168 reduced LPS-induced motor deficits without affecting anxiety-like or anhedonic behavior. In primary mesencephalic cultures, TPNA10168 inhibited microglial activation and nitric oxide production and protected dopaminergic neurons against LPS/interferon-γ-induced toxicity. The results suggest that TPNA10168 exerts partial anti-inflammatory effects in vivo and protects dopaminergic neurons from inflammation-induced damage in vitro, which indicates its potential as a therapeutic agent for inflammation-related neurological disorders.