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.

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.

Purpose: Identifying and managing risk factors for lower urinary tract symptoms (LUTS) is crucial because it impacts the quality of life of elderly individuals. Lifestyle factors, including physical activity (PA), and their relationship with LUTS have not been well studied. This objective of this study was to investigate the association between PA and LUTS. Materials and Methods: A total of 7,296 men were included in this cross-sectional study. PA was quantified in metabolic equivalent (MET)-hours per week, and LUTS severity was assessed using the international prostate symptom score. Logistic regression was used to analyze the association between PA and LUTS, including voiding and storage symptoms. Results: The average age of the participants was 57.8 years, and the prevalence of LUTS was 41.3%. After adjusting for potential confounders, PA was inversely associated with the prevalence and severity of moderate-to-severe LUTS, showing a dose-response pattern (all p for trend <0.01). Compared to the minimal activity group, which engaged in <5 MET-hours per week of PA, the odds ratios for moderate to severe LUTS were 0.83 (95% confidence interval [CI]: 0.72–0.97) for men engaging in 15–30 MET-hours per week, 0.82 (95% CI: 0.71–0.95) for 30–60 MET-hours per week, and 0.72 (95% CI: 0.62–0.84) for ≥60 MET-hours per week. The possible protective effect of PA was still observed in the additional analysis for voiding and storage symptoms showing the same dose-response pattern (all p for trend <0.01). Conclusions A higher PA level was associated with a lower prevalence and severity of total, voiding, and storage LUTS in a dose-dependent manner in Korean men.

Purpose: Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF. Materials and Methods: A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusion We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.

Purpose: Identifying and managing risk factors for lower urinary tract symptoms (LUTS) is crucial because it impacts the quality of life of elderly individuals. Lifestyle factors, including physical activity (PA), and their relationship with LUTS have not been well studied. This objective of this study was to investigate the association between PA and LUTS. Materials and Methods: A total of 7,296 men were included in this cross-sectional study. PA was quantified in metabolic equivalent (MET)-hours per week, and LUTS severity was assessed using the international prostate symptom score. Logistic regression was used to analyze the association between PA and LUTS, including voiding and storage symptoms. Results: The average age of the participants was 57.8 years, and the prevalence of LUTS was 41.3%. After adjusting for potential confounders, PA was inversely associated with the prevalence and severity of moderate-to-severe LUTS, showing a dose-response pattern (all p for trend <0.01). Compared to the minimal activity group, which engaged in <5 MET-hours per week of PA, the odds ratios for moderate to severe LUTS were 0.83 (95% confidence interval [CI]: 0.72–0.97) for men engaging in 15–30 MET-hours per week, 0.82 (95% CI: 0.71–0.95) for 30–60 MET-hours per week, and 0.72 (95% CI: 0.62–0.84) for ≥60 MET-hours per week. The possible protective effect of PA was still observed in the additional analysis for voiding and storage symptoms showing the same dose-response pattern (all p for trend <0.01). Conclusions A higher PA level was associated with a lower prevalence and severity of total, voiding, and storage LUTS in a dose-dependent manner in Korean men.

Purpose: Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF. Materials and Methods: A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusion We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.

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.