• Preventive Nutrition and Food Science
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• 제14권4호
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• pp.269-276
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• 2009

Overproduction of reactive oxygen species (ROS), including nitric oxide (NO), could be associated with the pathogenesis of various diseases such as cancer and chronic inflammation. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are known to play key roles in the development of these diseases. Cedrela sinensis leaves have been used in Asian countries as a traditional remedy for enteritis, dysentery and itching. In the present study, we investigated the anti-inflammatory effects of Cedrela sinensis leaves in lipopolysaccharide (LPS)- stimulated RAW 264.7 macrophages. Powder of C. sinensis leaves was extracted with 95% ethanol and fractionated with a series of organic solvents including n-hexane, dichloromethane, ethyl acetate, n-butanol, and water. The dichloromethane (DCM) fraction strongly inhibited NO production possibly by down-regulating iNOS and COX-2 expression, as determined by Western blotting. Hydrogen peroxide-induced generation of reactive oxygen species (ROS) was also effectively inhibited by the DCM fraction from C. sinensis leaves. In addition, C. sinensis inhibited LPS-mediated p65 activation via the prevention of IκB-$\alpha$ phosphorylation. Furthermore, mitogen-activated protein kinases (MAPKs) such as ERK 1/2 and p38 were found to affect the expression of iNOS and COX-2 in the cells. Taken together, our data suggest that leaves of C. sinensis could be used as a potential source for anti-inflammatory agents.

• 한국콘텐츠학회논문지
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• 제19권11호
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• pp.375-382
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• 2019

임신 초기 염증으로 인한 영양막세포의 기능 이상은 C-reactive protein (CRP)의 발현을 증가시켜 산모와 태아의 상호작용에 영향을 미침으로써, 조산 및 자간전증 등을 유발한다. 그러나, CRP 발현 조절과 관련된 생체표지자 발굴 및 개발은 미흡한 실정이다. 본 연구는 염증이 유발된 영양막세포에서 증가된 CRP 발현과 관련된 miRNA를 발굴 및 그 발현을 분석함으로써, miRNA를 통해 영양막세포 염증 조절 기전에 관여하는 생체표지자를 밝히고자 한다. miRNA 데이터베이스(mirna, TargetScan, MicroCosm)에서 공통적으로 CRP 유전자 발현을 조절할 것으로 예측되는 miR-7, miR-150, miR-186, 그리고 miR-424를 선별하여 HTR-8/SVneo에 LPS (20ng/mL)를 처리하여 in vitro 상에서 염증 반응을 유도하였다. 각각의 miRNAs의 발현을 qRT-PCR 방법으로 비교 분석하였다. 그 결과, LPS 처리된 영양막세포에서 CRP의 발현은 유의성 있게 증가되었다(p<0.001). miR-150와 miR-424는 발현이 유의성 있게 감소됨을 확인하였다(p<0.001). 따라서, 염증이 유도된 영양막세포에서의 CRP 발현을 조절하는 기전에 miR-150와 miR-424가 관여하는 것을 의미하며, 향후 염증성 산과질환의 산전 진단에 유용한 자료로 사용될 것으로 사료된다.

• Journal of Periodontal and Implant Science
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• 제45권1호
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• pp.14-22
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• 2015

Purpose: The purpose of this study was to compare serum amyloid A (SAA) protein levels with high-sensitive C-reactive protein (hs-CRP) levels as markers of systemic inflammation in patients with chronic periodontitis. The association of serum titers of antibodies to periodontal microbiota and SAA/hs-CRP levels in periodontitis patients was also studied. Methods: A total of 110 individuals were included in this study. Patients were assessed for levels of hs-CRP and SAA. Nonfasting blood samples were collected from participants at the time of clinical examination. The diagnosis of adipose tissue disorders was made according to previously defined criteria. To determine SAA levels, a sandwich enzyme-linked immunosorbent assay was utilized. Paper points were transferred to a sterile tube to obtain a pool of samples for polymerase chain reaction processing and the identification of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia. The serum level of IgG1 and IgG2 antibodies to P. gingivalis, A. actinomycetemcomitans, and T. forsythia was also determined. Results: SAA and hs-CRP levels were higher in periodontitis patients than in controls (P<0.05). In bivariate analysis, high levels of hs-CRP (>3 mg/L) and SAA (>10 mg/L) were significantly associated with chronic periodontitis (P=0.004). The Spearman correlation analysis between acute-phase proteins showed that SAA positively correlated with hs-CRP (r=0.218, P=0.02). In the adjusted model, chronic periodontitis was associated with high levels of SAA (odds ratio [OR], 5.5; 95% confidence interval [CI], 1.6-18.2; P=0.005) and elevated hs-CRP levels (OR, 6.1, 95% CI, 1.6-23.6; P=0.008). Increased levels of serum IgG2 antibodies to P. gingivalis were associated with high levels of SAA (OR, 3.6; 95% CI, 1.4-8.5; P=0.005) and high concentrations of hs-CRP (OR, 4.3; 95% CI, 1.9-9.8; P<0.001). Conclusions: SAA and hs-CRP concentrations in patients with chronic periodontitis are comparably elevated. High serum titers of antibodies to P. gingivalis and the presence of periodontal disease are independently related to high SAA and hs-CRP levels.

• 농업과학연구
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• 제46권2호
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• pp.369-379
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• 2019

Alzheimer's disease (AD) is the most common neurodegenerative disease associated with age, and amyloid beta ($A{\beta}$) is known to cause Alzheimer's disease. In the present study, we investigated the protective effects of Cirsium japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells. The cells treated with $A{\beta}_{25-35}$ showed a decrease in cell viability and an increase in reactive oxygen species (ROS) production compared with the non-treated cells. However, the cells treated with the C. japonicum var. maackii extract and its fractions increased the cell viability and inhibited the $A{\beta}$-induced ROS production. These results demonstrate the neuroprotective effects of C. japonicum var. maackii against $A{\beta}$. To further examine the protective mechanism, we measured inflammation and apoptosis related protein expressions. The cells treated with extract and fractions from C. japonicum var. maackii down-regulated inflammatory related proteins such as cyclooxygenase-2, interleukin $(IL)-1{\beta}$, and IL-6, and attenuated apoptosis related proteins including B-cell lymphoma-2 (Bcl-2) associated X protein/Bcl-2 ratio. In particular, the ethanol and ethylacetate fraction exhibited higher inhibitory effect against ROS production and apoptosis-related protein expressions among the extract and the other fractions. Therefore, this study demonstrated the protective effects of C. japonicum var. maackii extract and its fractions against $A{\beta}$-induced neurotoxicity in C6 glial cells through the regulation of oxidative stress, inflammation, and apoptosis, suggesting that it might have potential as a therapeutic for AD.

• Journal of Preventive Medicine and Public Health
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• 제48권5호
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• pp.249-256
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• 2015

Objectives: Epidemiological studies have reported that vitamin D deficiency is associated with inflammatory disease. Smoking is a well-known risk factor for inflammation. However, few studies have investigated the interactive effect of vitamin D deficiency and smoking on inflammation. This study aims to investigate the interaction of vitamin D and smoking with inflammatory markers in the urban elderly. Methods: We used data from the Korean Elderly Environmental Panel Study, which began in August 2008 and ended in August 2010, and included 560 Koreans ${\geq}60$ years old living in Seoul. Data was collected via questionnaires that included items about smoking status at the first visit. Vitamin D levels, high-sensitivity C-reactive protein (hs-CRP), and white blood cell (WBC) counts were repeatedly measured up to three times. Results: The association of vitamin D and hs-CRP was significant after adjusting for known confounders (${\beta}=-0.080$, p=0.041). After separate analysis by smoking status, the association of vitamin D deficiency and hs-CRP in smokers was stronger than that in nonsmokers (smokers: ${\beta}=-0.375$, p=0.013; non-smokers: ${\beta}=-0.060$, p=0.150). Smoking status was an effect modifier that changed the association between vitamin D deficiency and hs-CRP (interaction estimate: ${\beta}=-0.254$, p=0.032). Vitamin D was not significantly associated with WBC count (${\beta}=0.003$, p=0.805). Conclusions: Vitamin D deficiency was associated with hs-CRP in the urban elderly. Smoking status was an effect modifier of this association. Vitamin D deficiency was not significantly associated with WBC count.

• 한국산업보건학회지
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• 제30권2호
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• pp.196-204
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• 2020

Objective: Chronic obstructive pulmonary disease(COPD) is characterized by persistent airflow limitations associated with chronic inflammatory response due to noxious particles or gases in the lung. Increasing oxidative stress associated with COPD. The aim of this study was to evaluate the influencing factors of biomarkers for oxidative stress in retired miners with COPD. Methods: The levels of total peroxide(TPx), total antioxidant capacity(TAC), and oxidative stress index(TPx/TAC ratio, OSI) in plasma as biomarkers for oxidative stress, serum C-reactive protein(CRP) as a biomarker for inflammation, and general characteristics were measured in 93 male subjects with COPD. COPD was defined as post bronchodilator FEV₁/FVC<0.7 by spirometry. Results: Mean levels of TPx(p=0.013), TAC(p=0.010), OSI(p=0.040), and CRP(p=0.024) were higher in current smokers. Levels of TPx(β=0.445, p<0.001), TAC(β=0.490, p<0.001), and OSI(β=0.351, p<0.001) were related to CRP levels, and CRP levels were related to %FEV₁ predicted(β=-0.295, p=0.003) and current smoking(β=0.214, p=0.032). Conclusions: These results suggest that oxidative stress was related to inflammation, and inflammation were related to decreasing %FEV₁ predicted and current smoking in retired miners with COPD.

• 한국산업보건학회지
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• 제29권3호
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• pp.404-413
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• 2019

Objectives: Chronic obstructive pulmonary disease(COPD) is an important cause of mortality in workers exposed to hazardous dust, such as crystalline silica or coal, and COPD is related to inflammation and oxidative stress in the lung. The aim of this study was to evaluate the association of oxidative stress and inflammation to COPD in retired workers exposed to mineral dust. Methods: The levels of malondialdehyde(MDA) in EBC as biomarkers for oxidative stress and C-reactive protein(CRP) and lactate dehydrogenase(LD) as biomarkers for inflammation were measured in 107 male subjects(63 pneumoconiosis and 42 COPD subjects). Results: Mean levels of EBC MDA(2.03 nmol/L vs. 4.65 nmol/L, p=0.010) and serum LD(170.3 U/L vs. 185.9 U/L, p=0.022) were significantly higher in subjects with COPD, but mean levels of serum CRP(p=0.469) did not show a statistical difference between the study groups. Level of EBC MDA was negatively correlated with ${%}FEV_1$ predicted(r=-0.279, p=0.004) and ${%}FEV_1/FVC$ ratio(r=-0.397, p<0.001). Conclusions: These results suggest that EBC is a useful biological matrix for investigation of respiratory oxidative stress. High levels of EBC MDA and serum LD are related to COPD in retired workers exposed to mineral dust.

• 한국식생활문화학회지
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• 제35권5호
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• pp.493-502
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• 2020

The objective of this study was to investigate the effects of dietary vitamin B intake on biomarkers related to lipid metabolism, inflammation and blood glucose control, that are important in the development of type 2 diabetes and its complications. Seventy-six adults (42 males, 34 females) were recruited from a group of diabetes patients who had visited the medical center for treatment. Data on anthropometric characteristics and dietary intake of thiamine, riboflavin, niacin, vitamin B₆ and folate were collected using 24-hour diet recall and the CAN Pro 4.0 program. Also, data on clinical indices such as serum lipids, blood pressure, high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c) and homeostasis model assessment 2-insulin resistance (HOMA2-IR) were collected and analyzed for correlation with dietary vitamin B intake. Results from the dietary intake survey showed that riboflavin and folate intake (in males) and folate intake (in females) were below the Dietary Reference Intake for Koreans. Statistical analysis revealed a negative correlation between hs-CRP and dietary intake of B vitamins. Riboflavin intake was inversely associated with systolic blood pressure after adjustments for age, BMI, smoking, alcohol consumption, exercise, ingestion of diabetes mellitus medication and energy intake (p<0.05). Our results suggest that dietary vitamin B may influence inflammation and consequently may help in better management of type 2 diabetes.

• BMB Reports
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• 제54권6호
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• pp.317-322
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• 2021

CCCTC-binding factor (CTCF), a zinc finger protein, is a transcription factor and regulator of chromatin structure. Forebrain excitatory neuron-specific CTCF deficiency contributes to inflammation via enhanced transcription of inflammation-related genes in the cortex and hippocampus. However, little is known about the long-term effect of CTCF deficiency on postnatal neurons, astrocytes, or microglia in the hippocampus of adult mice. To address this, we knocked out the Ctcf gene in forebrain glutamatergic neurons (Ctcf cKO) by crossing Ctcf-floxed mice with Camk2a-Cre mice and examined the hippocampi of 7.5-10-month-old male mice using immunofluorescence microscopy. We found obvious neuronal cell death and reactive gliosis in the hippocampal cornu ammonis (CA)1 in 7.5-10-month-old cKO mice. Prominent rod-shaped microglia that participate in immune surveillance were observed in the stratum pyramidale and radiatum layer, indicating a potential increase in inflammatory mediators released by hippocampal neurons. Although neuronal loss was not observed in CA3, and dentate gyrus (DG) CTCF depletion induced a significant increase in the number of microglia in the stratum oriens of CA3 and reactive microgliosis and astrogliosis in the molecular layer and hilus of the DG in 7.5-10-month-old cKO mice. These results suggest that long-term Ctcf deletion from forebrain excitatory neurons may contribute to reactive gliosis induced by neuronal damage and consequent neuronal loss in the hippocampal CA1, DG, and CA3 in sequence over 7 months of age.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3369-3375
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• 2014

Background: C-reactive protein (CRP), considered as a prototypical inflammatory cytokine, has been proposed to be involved in tumor progression through inflammation. Recent studies have indicated CRP as a progostic predictor for urological cancers, but the results remain controversial. Materials and Methods: A systematic search of Medline, Scopus and the Cochrane Library was performed to identify eligible studies published between Jan 1, 2001 and Sep 1, 2013. Outcomes of interest were collected from studies comparing overall survival (OS), cancer-specific survival (CSS) and relapse-free survival (RFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratio (HR) of CRP with its 95% confidence interval (CI) for survival were used for the effect size estimate. Results: A total of 43 studies (7,490 patients) were included in this meta-analysis (25 for RCC, 10 for UC, and 8 for PC). Our pooled results showed that elevated serum CRP level was associated with poor OS (HR: 1.26, 95%CI: 1.22-1.30) and RFS (HR: 1.38 95%CI: 1.29-1.47), respectively. For CSS the pooled HR (HR: 1.33, 95%CI: 1.28-1.39) for higher CRP expression could strongly predict poorer survival in urological cancers. Simultaneously, elevated serum CRP was also significantly associated with poor prognosis in the subgroup analysis. Conclusions: Our pooled results demonstrate that a high serum level of CRP as an inflammation biomarker denotes a poor prognosis of patients with urological cancers. Further large prospective studies should be performed to confirm whether CRP, as a biomarker of inflammation, has a prognostic role in urological cancer progression.