Background: To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX. Results: The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 pro-tein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The ­ IC50 level to DOX was lower in both primary cells ­(IC50 = 0.12 μM and 0.20 μM) as compared to the CT26 cells ­(IC50 = 0.32  μM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7–23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8–254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells. Conclusions To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALENmediated Trp53 mutant gene.

Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/ 2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.

Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/ 2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.

Background/Aims: The clinical characteristics of patients with masked uncontrolled hypertension (MUCH) have been poorly defined, and few studies have investigated the clinical predictors of MUCH. We investigated the demographic, clinical, and blood pressure (BP) characteristics of patients with MUCH and proposed a prediction model for MUCH in patients with hypertension. Methods: We analyzed 1,986 subjects who were enrolled in the Korean Ambulatory Blood Pressure Monitoring (Kor-ABP) Registry and taking antihypertensive drugs, and classified them into the controlled hypertension (n = 465) and MUCH (n = 389) groups. MUCH was defined as the presence of a 24-hour ambulatory mean systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 80 mmHg in patients treated with antihypertensive drugs, having normal office BP. Results: Patients in the MUCH group had significantly worse metabolic profiles and higher office BP, and took significantly fewer antihypertensive drugs compared to those in the controlled hypertension group. Multivariate logistic regression analyses identified high office systolic BP and diastolic BP, prior stroke, dyslipidemia, left ventricular hypertrophy (LVH, ≥ 116 g/m2 for men, and ≥ 96 g/m2 for women), high heart rate (≥ 75 beats/min), and single antihypertensive drug use as independent predictors of MUCH. A prediction model using these predictors showed a high diagnostic accuracy (C-index of 0.839) and goodness-of-fit for the presence of MUCH. Conclusions MUCH is associated with a high-normal increase in office BP and underuse of antihypertensive drugs, as well as dyslipidemia, prior stroke, and LVH, which could underscore achieving optimal BP control. The proposed model accurately predicts MUCH in patients with controlled office BP.

Background/Aims: The clinical characteristics of patients with masked uncontrolled hypertension (MUCH) have been poorly defined, and few studies have investigated the clinical predictors of MUCH. We investigated the demographic, clinical, and blood pressure (BP) characteristics of patients with MUCH and proposed a prediction model for MUCH in patients with hypertension. Methods: We analyzed 1,986 subjects who were enrolled in the Korean Ambulatory Blood Pressure Monitoring (Kor-ABP) Registry and taking antihypertensive drugs, and classified them into the controlled hypertension (n = 465) and MUCH (n = 389) groups. MUCH was defined as the presence of a 24-hour ambulatory mean systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 80 mmHg in patients treated with antihypertensive drugs, having normal office BP. Results: Patients in the MUCH group had significantly worse metabolic profiles and higher office BP, and took significantly fewer antihypertensive drugs compared to those in the controlled hypertension group. Multivariate logistic regression analyses identified high office systolic BP and diastolic BP, prior stroke, dyslipidemia, left ventricular hypertrophy (LVH, ≥ 116 g/m2 for men, and ≥ 96 g/m2 for women), high heart rate (≥ 75 beats/min), and single antihypertensive drug use as independent predictors of MUCH. A prediction model using these predictors showed a high diagnostic accuracy (C-index of 0.839) and goodness-of-fit for the presence of MUCH. Conclusions MUCH is associated with a high-normal increase in office BP and underuse of antihypertensive drugs, as well as dyslipidemia, prior stroke, and LVH, which could underscore achieving optimal BP control. The proposed model accurately predicts MUCH in patients with controlled office BP.

Background: s: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes. Methods: This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed. Results: A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013).They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis (P = 0.008). Conclusion The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19.

BACKGROUND/AIMS: Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients. METHODS: In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication. RESULTS: Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died. CONCLUSIONS Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.

Trichomoniasis is the most common curable sexually-transmitted infection. Most Trichomonas vaginalis-infected men are asymptomatic and can remain undiagnosed and untreated, and this has been thought to result in chronic persistent prostatic infection. Chronic inflammation is regarded as the major factor in the pathogenesis and progression of benign prostatic hyperplasia (BPH) and prostatic cancer (PCa). The aim of this study is to identify seropositivity to T. vaginalis in men with prostate tumors (BPH or PCa) visited to Hanyang University Hospital. A total of 183 men were enrolled between October 2013 and November 2014. They consisted of 139 with BPH (mean age: 64.0±0.07) and 44 with prostate cancer (mean age: 73.3±0.18). We carried out ELISA to identify the seropositivity to T. vaginalis. Mixed lysate antigen extracted from 8 strains of T. vaginalis was used in the ELISA. Also 58 male outpatients visited to Health Promotion Center in Hanyang University Hospital were evaluated for comparing group. As a results, seropositivity to T. vaginalis in patients with prostatic diseases was 19.7% (BPH: 18.7%, PCa: 22.7%) and it was significantly higher than the 1.7% of the comparing healthy group (P=0.001). Therefore, prostatic tumor showed higher seropositivity against T. vaginalis than normal men. As far as we know, this is the first report about seroprevalence in prostatic tumor in Korea.
Enzyme-Linked Immunosorbent Assay ; Health Promotion ; Humans ; Inflammation ; Korea ; Male ; Outpatients ; Passive Cutaneous Anaphylaxis ; Prostate ; Prostatic Diseases ; Prostatic Hyperplasia ; Prostatic Neoplasms ; Seroepidemiologic Studies ; Trichomonas vaginalis ; Trichomonas