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Neuro-inflammation induced by restraint stress causes impairs neurobehavior in mice (스트레스 유발 마우스모델에서 뇌염증 및 신경행동 장애 변화)

  • Oh, Tae woo;Do, Hyun Ju;Kim, Kwang-Youn;Kim, Young Woo;Lee, Byung Wook;Ma, Jin Yeul;Park, Kwang Il
    • Herbal Formula Science
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    • v.25 no.4
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    • pp.483-497
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    • 2017
  • Background : Behavioral stress has been suggested as one of the significant factors that is able to disrupt physiological systems and cause depression as well as changes in various body systems. The stressful events can alter cognition, learning, memory and emotional responses, resulting in mental disorders such as depression and anxiety. Results : We used a restraint stress model to evaluate the alteration of behavior and stress-related blood parameter. The animals were randomly divided into two groups of five animals each group. Furthermore, we assessed the change of body weight to evaluate the locomotor activity as well as status of emotional and anxiety in mice. After 7 days of restraint stress, the body weight had significantly decreased in the restraint stress group compared with the control group. We also observed stress-associated behavioral alterations, as there was a significant decrease in open field and forced swim test, whereas the immobilization time was significantly increased in the stress group compared to the control group. We observed the morphological changes of neuronal death and microglia by immunohistochemistry and western blot. In our study restraint stress did not cause change in neuronal cell density in the frontal cortex and CA1 hippocampus region, but there was a trend for an increased COX-2 and iNOS protein expression and microglia (CD11b) in brain, which is restraint stress. Conclusion : Our study, there were significant alterations observed in the behavioral studies. We found that mice undergoing restraint stress changed behavior, confirming the increased expression of inflammatory factors in the brain.

Suppression of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice by transduced Tat-Annexin protein

  • Lee, Sun-Hwa;Kim, Dae-Won;Eom, Seon-Ae;Jun, Se-Young;Park, Mee-Young;Kim, Duk-Soo;Kwon, Hyung-Joo;Kwon, Hyeok-Yil;Han, Kyu-Hyung;Park, Jin-Seu;Hwang, Hyun-Sook;Eum, Won-Sik;Choi, Soo-Young
    • BMB Reports
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    • v.45 no.6
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    • pp.354-359
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    • 2012
  • We examined that the protective effects of ANX1 on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in animal models using a Tat-ANX1 protein. Topical application of the Tat-ANX1 protein markedly inhibited TPA-induced ear edema and expression levels of cyclooxygenase-2 (COX-2) as well as pro-inflammatory cytokines such as interleukin-1 beta (IL-$1{\beta}$), IL-6, and tumor necrosis factor-alpha (TNF-${\alpha}$). Also, application of Tat-ANX1 protein significantly inhibited nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) and phosphorylation of p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) in TPA-treated mice ears. The results indicate that Tat-ANX1 protein inhibits the inflammatory response by blocking NF-${\kappa}B$ and MAPK activation in TPA-induced mice ears. Therefore, the Tat-ANX1 protein may be useful as a therapeutic agent against inflammatory skin diseases.

A Cohort Study of Physical Activity and All Cause Mortality in Middle-aged Men in Seoul (서울시 중년남성에서 육체적 활동량이 총 사망률에 미치는 영향에 관한 코호트 연구)

  • Kim, Dae-Sung;Koo, Hye-Won;Kim, Dong-Hyon;Bae, Jong-Myon;Shin, Myung-Hee;Lee, Moo-Song;Lee, Chung-Min;Ahn, Yoon-Ok
    • Journal of Preventive Medicine and Public Health
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    • v.31 no.4 s.63
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    • pp.604-615
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    • 1998
  • Although previous studies revealed the association of physical activity with mortality rate, it is unclear whether there is a linear trend between physical activity and mortality rate. In this study, the association of physical activity with the risk of all-cause mortality was analysed using Cox's proportional hazard model for a cohort of 14,204 healthy Korean men aged 40-59 years followed up for 4 years(Jan. 1993-Dec. 1996). Physical activity and other life style were surveyed by a postal questionnaire in December 1992. Total of 14,204 subjects were grouped into quartiles by physical activity. Using death certificate data, 123 deaths were identified. The second most active quartile had a lowest mortality .ate with relative risk of 0.44(95% C.I. : 0.23-0.84) compared with most sedentary quartile, showing a J-shape pattern of physical activity-mortality curve. By examining the difference in proportion of cause of the death between most active quartile and the other quartiles, there was no significant difference of proportional mortality from cardiovascular deaths, cerebrovascular deaths or deaths from trauma. The covariates were stratified into two group between which the trend of RR was compared to test the effect modification. There was no remarkable effect modification by alcohol intake, smoking, body mass index, calorie consumption, percent fat consumption. In conclusion, moderate activity was found to have more protective effect on all-cause mortality than vigorous activity and that the J-shape pattern of physical activity-mortality curve was not due to the difference of mortality pattern or effect modification by alcohol intake, smoking, body mass index, calorie consumption and percent fat consumption.

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A Prospective Cohort Study on the Relationship of Sleep Duration With All-cause and Disease-specific Mortality in the Korean Multi-center Cancer Cohort Study

  • Yeo, Yohwan;Ma, Seung Hyun;Park, Sue Kyung;Chang, Soung-Hoon;Shin, Hai-Rim;Kang, Daehee;Yoo, Keun-Young
    • Journal of Preventive Medicine and Public Health
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    • v.46 no.5
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    • pp.271-281
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    • 2013
  • Objectives: Emerging evidence indicates that sleep duration is associated with health outcomes. However, the relationship of sleep duration with long-term health is unclear. This study was designed to determine the relationship of sleep duration with mortality as a parameter for long-term health in a large prospective cohort study in Korea. Methods: The study population included 13 164 participants aged over 20 years from the Korean Multi-center Cancer Cohort study. Information on sleep duration was obtained through a structured questionnaire interview. The hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using a Cox regression model. The non-linear relationship between sleep duration and mortality was examined non-parametrically using restricted cubic splines. Results: The HRs for all-cause mortality showed a U-shape, with the lowest point at sleep duration of 7 to 8 hours. There was an increased risk of death among persons with sleep duration of ${\leq}5$ hours (HR, 1.21; 95% CI, 1.03 to 1.41) and of ${\geq}10$ hours (HR, 1.36; 95% CI, 1.07 to 1.72). In stratified analysis, this relationship of HR was seen in women and in participants aged ${\geq}60$ years. Risk of cardiovascular disease-specific mortality was associated with a sleep duration of ${\leq}5$ hours (HR, 1.40; 95% CI, 1.02 to 1.93). Risk of death from respiratory disease was associated with sleep duration at both extremes (${\leq}5$ and ${\geq}10$ hours). Conclusions: Sleep durations of 7 to 8 hours may be recommended to the public for a general healthy lifestyle in Korea.

The Effects of DoDamTanghapChongMungTang(Daotantanghecongmingtang) on LPS induced-Microglia and Memory Deficit Mice Model (도담탕합총명탕(導痰湯合聰明湯)이 LPS로 처리된 microglia 및 기억력 감퇴 생쥐 모델에 미치는 영향)

  • Park, Dae-Myung;Lee, Sang-Ryong;Jung, In-Chul
    • Journal of Oriental Neuropsychiatry
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    • v.22 no.2
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    • pp.107-128
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    • 2011
  • Objectives : This experiment was designed to investigate the efficacy of DDTCMT hot water extract & ultra-fine powder on Alzheimer's Disease Model. Methods : The effects of the DDTCMT hot water extract on expression of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, NOS-II, IL-10, IL-1 receptor antagonist mRNA and production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by lipopolysacchaide(LPS) were investigated. Expression of NO, ROS in BV2 microglial cell line treated by LPS and AChE activity in PC-12 cell treated by NGF were investigated. anti-AChE was observed through Western blot analysis. The effects of the DDTCMT hot water extract & ultra-fine powder on the behavior of the memory deficit mice induced by scopolamine were investigated. Results : 1. The DDTCMT hot water extract significantly decreased the production of mIL-6, mNOS-II, mTNF-${\alpha}$, and increased the production of mIL-10, mIL-1 receptor antagonist. 2. The DDTCMT hot water extract significantly suppressed the production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by LPS. 3. The DDTCMT hot water extract significantly suppressed the NO and ROS production in BV2 microglial cell line treated by LPS. 4. The DDTCMT hot water extract groups showed inhibition of AChE activity in NGF treated PC-12 cell line. 5. The DDTCMT hot water extract suppressed anti-AChE expression in NGF treated PC-12 cell line was observed by Western blot analysis. 6. The DDTCMT hot water extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine -induced impairment of memory in the experiment of Morris water maze. Conclusions : These results suggest that the DDTCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease.

Anti-Inflammatory Activity of Ethanol Extract of Sargassum miyabei Yendo via Inhibition of NF-κB and MAPK Activation (NF-κB와 MAPKs 활성 저해를 통한 미야베 모자반(Sargassum miyabei Yendo) 에탄올 추출물의 항염증 활성)

  • Kim, Min-Ji;Bae, Nan-Young;Kim, Koth-Bong-Woo-Ri;Park, Sun-Hee;Jang, Mi-Ran;Im, Moo-Hyeog;Ahn, Dong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.44 no.4
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    • pp.442-451
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    • 2016
  • The aim of this study was to investigate the anti-inflammatory effect of Sargassum miyabei Yendo ethanol extract (SMYEE) using RAW 264.7 cells and croton oil-induced Balb/c mice. SMYEE inhibited the production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, and $IL-1{\beta}$] and nitric oxide in lipopolysaccharide (LPS)-induced inflammatory response. In addition, SMYEE suppressed the expression of inducible nitric oxide, cyclooxygenase-2, and nuclear factor-kappa B. Further, SMYEE inhibited the expression of mitogen-activated protein kinases (MAPKs), such as extra cellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase. In ear edema test, edema formation in the SMYEE treatment was lower than that in the positive control and was similar to that in the prednisolone treatment group. Photomicrographs of mice ear tissue showed a reduction in dermal thickness and number of infiltrated mast cells. Therefore, our results indicate that SMYEE exerts an anti-inflammatory effect via inhibition of nuclear factor ${NF}-{\kappa}B$ and MAPK activation and can be used as a natural source of anti-inflammatory compounds.

Comparison of the Anti-inflammatory Effects of the Extracts from Rubus coreanus and Rubus occidentalis (토종 복분자와 외래종 복분자 추출물의 항염증효과 비교)

  • Yang, Hyun-Mo;Lim, Soon-Sung;Lee, Yeon-Sil;Shin, Hyun-Kyung;Oh, Yang-Seok;Kim, Jin-Kyung
    • 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.

Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia over three Decades

  • Roder, David;Karapetis, Christos S;Wattchow, David;Moore, James;Singhal, Nimit;Joshi, Rohit;Keefe, Dorothy;Fusco, Kellie;Powell, Kate;Eckert, Marion;Price, Timothy J
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2431-2440
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    • 2015
  • Background: Registry data from four major public hospitals indicate trends in clinical care and survival from colorectal cancer over three decades, from 1980 to 2010. Materials and Methods: Kaplan-Meier productlimit estimates and Cox proportional hazards models were used to investigate disease-specific survival and multiple logistic regression analyses to explore first-round treatment trends. Results: Five-year survivals increased from 48% for 1980-1986 to 63% for 2005-2010 diagnoses. Survival increases applied to each ACPS stage (Australian Clinico-Pathological Stage), and particularly stage C (an increase from 38% to 68%). Risk of death from colorectal cancer halved (hazards ratio: 0.50 (0.45, 0.56)) over the study period after adjusting for age, sex, stage, differentiation, primary sub-site, health administrative region, and measures of socioeconomic status and geographic remoteness. Decreases in stage were not observed. Survivals did not vary by sex or place of residence, suggesting reasonable equity in service access and outcomes. Of staged cases, 91% were treated surgically with lower surgical rates for older ages and more advanced stage. Proportions of surgical cases having adjuvant therapy during primary courses of treatment increased for all stages and were highest for stage C (an increase from 5% in 1980-1986 to 63% for 2005-2010). Radiotherapy was more common for rectal than colonic cases. Proportions of rectal cases receiving radiotherapy increased, particularly for stage C where the increase was from 8% in 1980-1986 to 60% in 2005-2010. The percentage of stage C colorectal cases less than 70 years of age having systemic therapy as part of their first treatment round increased from 3% in 1980-1986 to 81% by 1995-2010. Based on survey data on uptake of adjuvant therapy among those offered this care, it is likely that all these younger patients were offered systemic treatment. Conclusions: We conclude that pronounced increases in survivals from colorectal cancer have occurred at major public hospitals in South Australia due to increases in stage-specific survivals. Use of adjuvant therapies has increased and the patterns of change accord with clinical guideline recommendations. Reasons for sub-optimal use of radiotherapy for rectal cases warrant further investigation, including the potential for limited rural access to impede uptake of treatments at metropolitan-based radiotherapy centres.

Evaluation of Biochemical Recurrence-free Survival after Radical Prostatectomy by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) Score

  • Aktas, Binhan Kagan;Ozden, Cuneyt;Bulut, Suleyman;Tagci, Suleyman;Erbay, Guven;Gokkaya, Cevdet Serkan;Baykam, Mehmet Murat;Memis, Ali
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2527-2530
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    • 2015
  • Background: The cancer of the prostate risk assessment (CAPRA) score has been defined to predict prostate cancer recurrence based on the pre-clinical data, then pathological data have also been incorporated. Thus, CAPRA post-surgical (CAPRA-S) score has been developed based on six criteria (prostate specific antigen (PSA) at diagnosis, pathological Gleason score, and information on surgical margin, seminal vesicle invasion, extracapsular extension and lymph node involvement) for the prediction of post-surgical recurrences. In the present study, biochemical recurrence (BCR)-free probabilities after open retropubic radical prostatectomy (RP) were evaluated by the CAPRA-S scoring system and its three-risk level model. Materials and Methods: CAPRA-S scores (0-12) of our 240 radical prostatectomies performed between January 2000-May 2011 were calculated. Patients were distributed into CAPRA-S score groups and also into three-risk groups as low, intermediate and high. BCR-free probabilities were assessed and compared using Kaplan-Meier analysis and Cox proportional hazards regression. Ability of CAPRA-S in BCR detection was evaluated by concordance index (c-index). Results: BCR was present in 41 of total 240 patients (17.1%) and the mean follow-up time was $51.7{\pm}33.0$ months. Mean BCR-free survival time was 98.3 months (95% CI: 92.3-104.2). Of the patients in low, intermediate and high risk groups, 5.4%, 22.0% and 58.8% had BCR, respectively and the difference among the three groups was significant (P = 0.0001). C-indices of CAPRA-S score and three-risk groups for detecting BCR-free probabilities in 5-yr were 0.87 and 0.81, respectively. Conclusions: Both CAPRA-S score and its three-risk level model well predicted BCR after RP with high c-index levels in our center. Therefore, it is a clinically reliable post-operative risk stratifier and disease recurrence predictor for prostate cancer.

Independent and Additive Interaction Between Tumor Necrosis Factor β +252 Polymorphisms and Chronic Hepatitis B and C Virus Infection on Risk and Prognosis of Hepatocellular Carcinoma: a Case-Control Study

  • Jeng, Jen-Eing;Wu, Hui-Fang;Tsai, Meng-Feng;Tsai, Huey-Ru;Chuang, Lea-Yea;Lin, Zu-Yau;Hsieh, Min-Yuh;Chen, Shinn-Chern;Chuang, Wan-Lung;Wang, Liang-Yen;Yu, Ming-Lung;Dai, Chia-Yen;Tsai, Jung-Fa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10209-10215
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    • 2015
  • To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.