Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

The roots of Astragalus membranaceus Bunge have long been used in herbal medicine for their diversebiological activities. Notably, its potential anti-diabetic properties have been extensively studied, highlighting promising therapeutic prospects. In this study, we conducted a comprehensive investigation focusing on flavonoid components from the roots of A. membranaceus and their PTP1B inhibitory activity. As a result, we isolated a total of 24 flavonoids, among which formonentin (1), pratensein (3), and vesticarpan (19) emerged as the most potent inhibitors against PTP1B with IC50 value of 10.9 ± 1.09 μM, 10.0 ± 1.71 μM, and 10.3 ± 1.31 μM, respectively.Additionally, through the enzyme kinetic analysis, the inhibition mode of compound 19 was determined as a competitive inhibitor, with Ki value of 7.6 ± 1.17 μM. Furthermore, the molecular docking simulation elucidated the binding mechanism of compound 19 with PTP1B, mainly through van der Waals forces and hydrogen bonds.This study highlights the PTP1B inhibitory potential of the flavonoid constituents derived from the roots of A. membranaceus. Moreover, discovering vesticarpan (19) as a novel PTP1B inhibitor provides a significant foundation for further investigations to develop innovative therapeutic strategies for diabetes treatment.

Purpose: This study aimed to characterize the clinical patterns and severity of brain injury in neonates who survived extracorporeal membrane oxygenation (ECMO) therapy for acute respiratory failure during the neonatal period, to evaluate their short-term neurodevelopmental outcomes, and to identify the factors associated with these outcomes. Methods: We retrospectively reviewed the medical records of neonates who survived ECMO between 2018 and 2024. Based on brain magnetic resonance imaging (MRI) findings, the patients were classified into two groups: no/mild and moderate/severe brain injury. Neurodevelopmental outcomes were assessed at 12–40 months of age using the Bayley Scale of Infant Development II/III and/or the Korean Developmental Screening Test. Results: Among the 19 neonates included in the study, 18 (94.7%) showed varying degrees of brain injury on MRI (mild: 12, moderate: 1, severe: 5). Neonates with moderate/severe brain injury had significantly longer durations of ECMO support and extended durations of mechanical ventilation and were more likely to receive continuous renal replacement therapy than those with no or mild injury. Developmental delay was identified in 36.8% of survivors and was significantly associated with prolonged mechanical ventilation, longer neonatal intensive care unit stays, and a higher incidence of seizures. Conclusion Brain injury is frequently observed on MRI in neonates treated with ECMO. However, its direct association with adverse neurodevelopmental outcomes is not definitive. Since MRI findings alone cannot predict developmental outcomes, clinical and environmental factors should be integrated into prognostic assessments.

Purpose: Emphysematous pyelonephritis (EPN) is a life-threatening disease requiring immediate treatment. This multicenter retrospective cohort study aimed to analyze the mortality rate and risk factors associated with EPN. Materials and Methods: Between January 2011 and February 2021, 217 patients diagnosed with EPN via computed tomography who visited 14 teaching hospitals were retrospectively analyzed. Clinical data, including age, sex, comorbidities, Huang and Tseng classification, hydronephrosis, acute kidney injury, blood and urine tests, surgical interventions, percutaneous drainage, and conservative treatments, were compared between the survival and death groups. Risk factors for mortality due to EPN were analyzed using univariate and multivariate methods. Results: The mean age of survivors and deceased patients was 67.8 and 69.0 years, respectively (p=0.136). The sex distribution (male/female) was 48/146 and 8/15, respectively (p=0.298). Of the 217 patients, 23 died, resulting in a mortality rate of 10.6%. In univariate analysis, the Huang and Tseng classification (p=0.004), platelet count (p=0.005), and acute kidney injury (p=0.007) were significantly associated with mortality from EPN. In multivariate analysis, only the Huang and Tseng classification (p=0.029) was identified as a risk factor. Mortality rates according to the Huang and Tseng classification were as follows: class I (5.88%), class II (7.50%), class IIIa (14.28%), class IIIb (25.00%), and class IV (23.07%). Conclusions EPN is associated with a high mortality rate. Among various clinical factors, the Huang and Tseng classification was the most significant indicator for predicting mortality.

Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and increased inflammation, leading to respiratory symptoms. This study aimed to identify the traits for COPD progression from mild to severe stages. Additionally, we explored the correlation between coronavirus disease-2019 (COVID-19) and COPD to uncover overlapping respiratory patterns. Materials and Methods: Bulk RNA sequencing was conducted on data from 43 healthy individuals and 39 COPD patients across one dataset (GSE239897) to distinguish COPD characteristics. Single-cell RNA analysis was then performed on samples from seven mild patients, seven moderate patients, and three severe patients from three datasets (GSE167295, GSE173896, and GSE227691) to analyze disease progression. Finally, single-nuclei RNA analysis was applied to data from seven healthy individuals and 20 COVID-19 patients from one dataset (GSE171524) to compare the two conditions. Results: Bulk RNA sequencing revealed enhanced inflammatory pathways in COPD patients, indicating increased inflammation.Single-cell RNA sequencing showed a stronger inflammatory response from mild to moderate COPD with a decrease from moderate to severe stages. COVID-19 displayed similar biological patterns to moderate COPD, suggesting that stage-specific COPD analysis could enhance COVID-19 management. Conclusion The analysis found that immune responses increased from mild to moderate stages but declined in severe cases, marked by reduced pulmonary T cell activation. The overlap between moderate COPD and COVID-19 suggests shared therapeutic strategies, warranting further investigation.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.