• The Journal of Internal Korean Medicine
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• v.42 no.1
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• pp.11-24
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• 2021

Objective: Chronic reflux esophagitis (CRE), characterized by esophageal mucosa ulcer, is caused by continuous backflow of gastric acid and consequent inflammation due to unstable gastroesophageal sphincter. The aim of the present study was to clarify the effect of an Arecae Semen and Coptidis Rhizoma mixture (AC-mix) on CRE. Methods: CRE was surgically induced in SD rats with three experimental groups used: normal; CRE control; and CRE treatment (200 mg/kg AC-mix). Blood and esophageal tissue were collected after two weeks of drug administration. The anti-oxidant activity of the AC-mix was measured by total polyphenol and total flavonoid contents as well as by radical scavenging activity with protein levels evaluated using western blotting. Results: CRE damage to the esophageal mucosa was significantly reduced in the AC-mix group as compared with the controls, and administration of the AC-mix was seen to inhibit NF-κBp65 activity. Consequently, the inactivation of NF-κBp65 significantly inhibited inflammatory mediators such as COX-2 and iNOS. Moreover, the anti-oxidant enzyme HO-1 significantly increased through activation of the Nrf2-Keap1 pathway. Matrix metalloproteinase-2 (MMP-2), which can break down collagen from the basement membrane and extracellular matrix, was decreased following AC-mix treatment, and elevated levels of MMP-2 were regulated by its tissue inhibitor. Conclusions: These results show that AC-mix can alleviate esophageal mucosa ulcer though inhibition of the NF-κBp65 inflammatory pathway and enhancement of the anti-oxidant Nrf2-Keap1 pathway.

• Nutrition Research and Practice
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• v.16 no.5
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• pp.549-564
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• 2022

BACKGROUND/OBJECTIVES: Oxidative stress is caused by an imbalance between harmful free radicals and antioxidants. Long-term oxidative stress can lead to an "exhausted" status of antioxidant defense system triggering development of metabolic syndrome and chronic inflammation. Green perilla (Perilla frutescens) is commonly used in Asian cuisines and traditional medicine in southeast Asia. Green perilla possesses numerous beneficial effects including anti-inflammatory and antioxidant functions. To investigate the potentials of green perilla leaf extract (PE) on oxidative stress, we induced oxidative stress by high-fat diet (HFD) in aging mice. MATERIALS/METHODS: C57BL/6J male mice were fed HFD continuously for 53 weeks. Then, mice were divided into three groups for 12 weeks: a normal diet fed reference group (NDcon), high-fat diet fed group (HDcon), and high-fat diet PE treated group (HDPE, 400 mg/kg of body weight). Biochemical analyses of serum and liver tissues were performed to assess metabolic and inflammatory damage and oxidative status. Hepatic gene expression of oxidative stress and inflammation related enzymes were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: PE improved hepatopathology. PE also improved the lipid profiles and antioxidant enzymes, including hepatic glutathione peroxidase (GPx) and superoxide dismutase (SOD) and catalase (CAT) in serum and liver. Hepatic gene expressions of antioxidant and anti-inflammatory related enzymes, such as SOD-1, CAT, interleukin 4 (IL-4) and nuclear factor erythroid 2-related factor (Nrf2) were significantly enhanced by PE. PE also reduced the levels of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) in the serum and liver; moreover, PE suppressed hepatic gene expression involved in pro-inflammatory response; Cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CONCLUSIONS: This research opens opportunities for further investigations of PE as a functional food and possible anti-aging agent due to its attenuative effects against oxidative stress, resulting from HFD and aging in the future.

• Journal of Preventive Medicine and Public Health
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• v.56 no.3
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• pp.282-290
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• 2023

Objectives: This study aimed to evaluate the potential interaction between kidney function and the non-linear association between serum calcium levels and cardiovascular disease (CVD) mortality. Methods: This study included 8927 participants enrolled in the Dong-gu Study. Albumin-corrected calcium levels were used and categorized into 6 percentile categories: <2.5th, 2.5-25.0th, 25.0-50.0th, 50.0-75.0th, 75.0-97.5th, and >97.5th. Restricted cubic spline analysis was used to examine the non-linear association between calcium levels and CVD mortality. Cox proportional hazard regression was used to estimate hazard ratios (HRs) for CVD mortality according to serum calcium categories. All survival analyses were stratified by the estimated glomerular filtration rate. Results: Over a follow-up period of 11.9±2.8 years, 1757 participants died, of whom 219 died from CVD. A U-shaped association between serum calcium and CVD mortality was found, and the association was more evident in the low kidney function group. Compared to the 25.0-50.0th percentile group for serum calcium levels, both low and high serum calcium tended to be associated with CVD mortality (<2.5th: HR, 6.23; 95% confidence interval [CI], 1.16 to 33.56; >97.5th: HR, 2.56; 95% CI, 0.76 to 8.66) in the low kidney function group. In the normal kidney function group, a similar association was found between serum calcium levels and CVD mortality (<2.5th: HR, 1.37; 95% CI, 0.58 to 3.27; >97.5th: HR, 1.65; 95% CI, 0.70 to 3.93). Conclusions: We found a non-linear association between serum calcium levels and CVD mortality, suggesting that calcium dyshomeostasis may contribute to CVD mortality, and kidney function may modify the association.

• Journal of Life Science
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• v.32 no.3
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• pp.210-221
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• 2022

This study investigated the mechanisms underlying the anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) in human cancer cells in combination with either N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, or MHY2245, a new synthetic sirtuin 1 inhibitor. The results showed both DAPT and MHY2245 as novel chemosensitizers of human colon cancer KM12 and human hepatocellular carcinoma SNU475 cells to NSAIDs involving celecoxib and 2, 5-dimethyl celecoxib. The NSAID-induced cytotoxicity of these cells was significantly increased by DAPT and MHY2245 in a cyclooxygenase-2 independent manner. In addition, DAPT and MHY2245 reduced levels of p62, Notch1 intracellular domain, and multiple cancer stemness (CS)-related markers including Notch1, CD44, CD133, octamer-binding transcription factor 4, mutated p53 and c-Myc. However, the level of activating transcription factor 4 (ATF4) was enhanced, probably indicating the down-regulation of multiple CS-related markers by DAPT or MHY2245-mediated autophagy induction. Moreover, the NSAID-mediated reduction of p62/nuclear factor erythroid-derived 2-like 2 and CS-related marker proteins and the up-regulation of C/EBP homologous protein (CHOP)/ATF4 were accelerated by DAPT and MHY2245. As such, the combination of NSAID and either DAPT or MHY2245 resulted in higher cytotoxicity than NSAID alone by accelerating the down-regulation of multiple CS-related markers and PARP activation, indicating that both inhibitors promote NSAID-mediated autophagic cell death, possibly through the CHOP/ATF4 pathway. In conclusion, either combination strategy may be useful for the effective treatment of human cancer cells expressing CS-related markers.

• Korean Journal of Radiology
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• v.24 no.5
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• pp.434-443
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• 2023

Objective: To investigate the association between pelvic bone computed tomography (CT)-derived body composition and patient outcomes in older adult patients who underwent surgery for proximal femur fractures. Materials and Methods: We retrospectively identified consecutive patients aged ≥ 65 years who underwent pelvic bone CT and subsequent surgery for proximal femur fractures between July 2018 and September 2021. Eight CT metrics were calculated from the cross-sectional area and attenuation of the subcutaneous fat and muscle, including the thigh subcutaneous fat (TSF) index, TSF attenuation, thigh muscle (TM) index, TM attenuation, gluteus maximus (GM) index, GM attenuation, gluteus medius and minimus (Gmm) index, and Gmm attenuation. The patients were dichotomized using the median value of each metric. Multivariable Cox regression and logistic regression models were used to determine the association between CT metrics with overall survival (OS) and postsurgical intensive care unit (ICU) admission, respectively. Results: A total of 372 patients (median age, 80.5 years; interquartile range, 76.0-85.0 years; 285 females) were included. TSF attenuation above the median (adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.41-4.05), GM index below the median (adjusted HR, 2.63; 95% CI, 1.33-5.26), and Gmm index below the median (adjusted HR, 2.33; 95% CI, 1.12-4.55) were independently associated with shorter OS. TSF index (adjusted odds ratio [OR], 6.67; 95% CI, 3.13-14.29), GM index (adjusted OR, 3.45; 95% CI, 1.49-7.69), GM attenuation (adjusted OR, 2.33; 95% CI, 1.02-5.56), Gmm index (adjusted OR, 2.70; 95% CI, 1.22-5.88), and Gmm attenuation (adjusted OR, 2.22; 95% CI, 1.01-5.00) below the median were independently associated with ICU admission. Conclusion: In older adult patients who underwent surgery for proximal femur fracture, low muscle indices of the GM and gluteus medius/minimus obtained from their cross-sectional areas on preoperative pelvic bone CT were significant prognostic markers for predicting high mortality and postsurgical ICU admission.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.289-294
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• 2016

Background: The aim of our study was to evaluate the prognostic value of Charlson's weighted index of comorbidities (WIC) in patients with prolonged acute mechanical ventilation (PAMV, ventilator care ${\geq}96$ hours). Methods: We retrospectively enrolled 299 Korean PAMV patients who were admitted in a medical intensive care unit (ICU) of a university-affiliated tertiary care hospital between 2008 and 2013. Survivors were defined as patients who survived for 60 days after ICU admission. Results: The patients' mean age was $65.1{\pm}14.1$ years and 70.6% were male. The mean ICU and hospital length of stay was $21.9{\pm}19.7$ and $39.4{\pm}39.1$ days, respectively. In addition, the 60-day mortality rate after ICU admission was 35.5%. The mean WIC was $2.3{\pm}1.8$, with significant differences between nonsurvivors and survivors ($2.7{\pm}2.1$ vs. $2.1{\pm}1.7$, p<0.05). The area under the curve of receiver-operating-characteristics curve for WIC was 0.593 (95% confidence interval [CI], 0.523-0.661; p<0.05). Based on Kaplan-Meier curves of 60-day survival, WIC ${\geq}5$ had statistically lower survival than WIC <5 (logrank test, p<0.05). In a multivariate Cox proportional hazard model, WIC ${\geq}5$ was associated with poor prognosis (hazard ratio, 1.901; 95% CI, 1.140-3.171; p<0.05). The mortality rate of patients with WIC ${\geq}5$ was 54.2%. Conclusion: Our study showed a WIC score ${\geq}5$ might be helpful in predicting 60-day mortality in PAMV patients.

• Korean Journal of Food Science and Technology
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• v.39 no.3
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• pp.342-347
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• 2007

The dried fruit of the Rubus coreanus, which is well-known in Korea and referred to as 'Bokbunja,' has been employed as a traditional medicine for centuries. This crude drug has been utilized in Korea for the management of impotence, spermatorrhea, enuresis, asthma, and allergic diseases. Our previous study demonstrated that the ethanol extracts of R. coreanus have anti-inflammatory effects. The principal objective of the present study was to conduct a comparison of the anti-inflammatory effects of the ethanol extracts of R. coreanus and R. occidentalis; here, we tested the unripe (URCE), half-ripened (HRCE), and ripened fruits (RCE) of R. coreanus, and the unripe (UROE), half-ripened (HROE), and ripened fruits (ROE) of R. occidentalis. We found that URCE, UROE, HRCE, and HROE reduced the production of nitric oxide and prostaglandin $E_{2}$ as well as pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 murine macrophages. Interestingly, the R. coreanus extracts showed stronger inhibitory effects on the production of these inflammatory mediators than the R. occidentalis extracts.

• Journal of Chest Surgery
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• v.51 no.4
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• pp.266-272
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• 2018

Background: Limited comparative data are available on the efficacy of cryoablation versus radiofrequency ablation in patients with atrial fibrillation. This study aimed to compare radiofrequency ablation and cryoablation with regard to clinical outcomes and the restoration of sinus rhythm or atrial contractility. Methods: A total of 239 patients who underwent surgical ablation between August 2003 and December 2016 at our institution were included. The patients were divided into 2 groups according to the energy device that was used (group A: n=140, radiofrequency ablator; group B: n=99, cryoablator). Echocardiographic data, overall survival, and major cardiovascular and cerebrovascular event (MACCE)-free survival were compared between the 2 groups. Results: At 1 year of follow-up, the atrial contractility recovery rate was 32.2% (19 of 59) in group A and 48.8% (21 of 44) in group B. In addition, cryoablation was found to be a predictive factor for the recovery of atrial contractility (cryoablation vs. radiofrequency ablation: odds ratio, 2.540; 95% confidence interval, 1.063-6.071; p=0.036). The left ventricular ejection fraction was significantly higher in group B ($53.1%{\pm}11.5%$ vs. $59.1%{\pm}6.3%$, p=0.001). The median follow-up duration was 36 months. The 5-year overall survival rate was $80.1%{\pm}3.6%$ in group A and $92.1%{\pm}2.9%$ in group B (p=0.400). The 5-year MACCE-free survival rate was $70.3%{\pm}4.0%$ in group A and $70.9%{\pm}5.6%$ in group B (p=0.818). Conclusion: Cryoablation was associated with a higher atrial contractility restoration rate and better left ventricular function than radiofrequency ablation. However, no significant relationship was observed between the energy source and overall or MACCE-free survival.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.98-98
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• 2018

In this study, we evaluated the anti-inflammatory effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia theezans in LPS-stimulated RAW264.7 cells. ST-L and ST-B significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, COX-2, $IL-1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. ST-L and ST-B blocked LPS-induced degradation of $I{\kappa}B-{\alpha}$ and nuclear accumulation of p65, which resulted to the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. ST-L and ST-B also attenuated the phosphorylation of ERK1/2, p38 and JNK in LPS-stimulated RAW264.7 cells. In addition, ST-L and ST-B increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of ST-L and ST-B against LPS-induced NO production in RAW264.7 cells. Inhibition of p38 activation and ROS elimination attenuated HO-1 expression by ST-L and ST-B, and ROS elimination inhibited p38 activation induced by ST-L and ST-B. ST-L and ST-B dramatically induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 activation and ROS elimination. Collectively, our results suggest that ST-L and ST-B exerts potential anti-inflammatory activity by suppressing $NF-{\kappa}B$ and MAPK signaling activation, and activating HO-1 expression through the nuclear accumulation of Nrf2 via ROS-dependent p38 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.

• Journal of Preventive Medicine and Public Health
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• v.38 no.2
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• pp.203-207
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• 2005

Objectives: Recently, the American Diabetes Association (ADA) redefined the criteria of prediabetes, which has lowered the diagnostic level of fasting plasma glucose (FPG) from 110 to 125 mg/dl, down to levels between 100 to 125mg/dl. The purpose of this study was to determine the predictive cutoff level of FPG as a risk for the development of diabetes mellitus in Korean men. Methods: A retrospective cohort study was conducted on 11,423 (64.5%) out of 17,696 males $\leq$30 years of age, and who met the FPG of $\leq$125 mg/dl and hemoglobin A1c of $\leq$ 6.4% criteria, without a history of diabetes, and who were enrolled at the screening center of a certain university hospital between January and December 1999. The subjects were followed from January 1999 to December 2002 (mean follow-up duration; 2.3(${\pm}0.7$) years). They were classified as normal (FPG <100mg/dl), high glucose (FPG $\geq$100mg/dl and <110mg/dl) and impaired fasting glucose (FPG $\geq$110mg/dl and $\leq$125mg/dl) on the basis of their fasting plasma glucose level measured in 1999. We compared the incidence of diabetes between the 3 groups by performing Cox proportional hazards model and used receiver operating characteristic analyses of the FPG level, in order to estimate the optimal cut-off values as predictors of incident diabetes. Results: At the baseline, most of the study subjects were in age in their 30s to 40s (mean age, 41.8(${\pm}7.1$) year). The incidence of diabetes mellitus in this study was 1.19 per 1,000 person-years (95% CI=0.68-1.79), which was much lower than the results of a community-based study that was 5.01 per 1,000 person-years. The relative risks of incident diabetes in the high glucose and impaired fasting glucose groups, compared with the normal glucose group, were 10.3 (95% CI=2.58-41.2) and 95.2 (95% CI= 29.3-309.1), respectively. After adjustment for age, body mass index, and log triglyceride, a FPG greater than 100mg/dl remained significant predictors of incident diabetes. Using the receiver operating characteristic (ROC) curve, the optimal cutoff level of FPG as a predictor of incident diabetes was 97.5 mg/dl, with a sensitivity and a specificity of 81.0% and 86.0%, respectively. Conclusion: These results suggest that lowering the criteria of impaired fasting glucose is needed in Korean male adults. Future studies on community-based populations, including women, will be required to determine the optimal cutoff level of FPG as a predictor of incident diabetes.