• Biomolecules & Therapeutics
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• 제21권1호
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• pp.1-9
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• 2013

Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.158-164
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• 2017

Methylglyoxal (MGO) is a highly reactive metabolite of glucose which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Hypericin, a naphthodianthrone isolated from Hypericum perforatum L. (St. John's Wort), is a potent and selective inhibitor of protein kinase C and is reported to reduce neuropathic pain. In this work, we investigated the protective effect of hypericin on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Hypericin showed significant anti-apoptotic activity in MGO-treated HUVECs. Pretreatment with hypericin significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. Hypericin prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. MGO was found to activate mitogen-activated protein kinases (MAPKs). Pretreatment with hypericin strongly inhibited the activation of MAPKs, including P38, JNK, and ERK1/2. Interestingly, hypericin also inhibited the formation of AGEs. These findings suggest that hypericin may be an effective regulator of MGO-induced apoptosis. In conclusion, hypericin downregulated the formation of AGEs and ameliorated MGO-induced dysfunction in human endothelial cells.

• Journal of Periodontal and Implant Science
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• 제44권4호
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• pp.158-168
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• 2014

Purpose: The present study was conducted to evaluate the impact of scaling and root planing (SRP) on the C-reactive protein (CRP) levels of gingival crevicular fluid (GCF) and serum in chronic periodontitis patients with type 2 diabetes mellitus (T2DM-CP) or without type 2 diabetes mellitus (NDM-CP). Methods: Forty-eight human participants were divided into two groups: an experimental (T2DM-CP) group (group I, n=24) comprising chronic periodontitis patients with random blood sugar ${\geq}200mg/dL$ and type 2 diabetes mellitus, and control (NDM-CP) group (group II, n=24) of those with chronic periodontitis and random blood sugar <200 without T2DM for the study. All subjects underwent nonsurgical periodontal therapy (NSPT) including complete SRP and subgingival debridement. Periodontal health parameters, plaque index (PI), gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL), GCF volume (GCF vol), GCF-CRP, random blood glucose (RBS), glycated hemoglobin, and systemic inflammatory markers, serum CRP, total leukocyte count (TLC), neutrophil count (Neutr) and lymphocyte count (Lymph), were evaluated at baseline, 1 month, and 3 months after SRP. Results: NSPT resulted in statistically significant improvement in periodontal health parameters (PI, GI, PPD, CAL, GCF vol), CRP levels in serum as well as GCF of both groups I and II. The mean improvement in periodontal health parameters (PI, GI, PPD, CAL, GCF vol), CRP levels in serum and GCF was greater in group I than group II after NSPT. There was nonsignificant increase in GCF-CRP, TLC, Lymph, and RBS, and a significant increase in Neutr and Serum CRP in group II at 1 month. The Serum CRP level of 20 out of 24 group II patients had also increased at 1 month. Conclusions: The CRP levels in both GCF and serum were higher in T2DM-CP patients than in NDM-CP patients. Although there was a significant improvement in both the groups, greater improvement was observed in both GCF and serum samples of T2DM-CP patients.

• Journal of Preventive Medicine and Public Health
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• 제49권5호
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• pp.275-287
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• 2016

Objectives: C-reactive protein (CRP), an inflammatory biomarker, has been widely used as a preclinical marker predictive of morbidity and mortality. Although many studies have reported a positive association between CRP and mortality, uncertainty still remains about this association in various populations, especially in rural Korea. Methods: A total of 23 233 middle-aged participants (8862 men and 14 371 women) who were free from cardiovascular disease, cancer, and acute inflammation (defined by a CRP level ${\geq}10mg/L$) were drawn from 11 rural communities in Korea between 2005 and 2011. Blood CRP concentration was analyzed as a categorical variable (low: 0.0-0.9 mg/L; intermediate: 1.0-3.0 mg/L; high: 3.1-9.9 mg/L) as well as a continuous variable. Each participant's vital status through December 2013 was confirmed by death statistics from the National Statistical Office. Cox proportional hazard models were used to assess the independent association between CRP and mortality after adjusting for other risk factors. Results: The total quantity of observed person-years was 57 975 for men and 95 146 for women, and the number of deaths was 649 among men and 367 among women. Compared to the low-CRP group, the adjusted hazard ratio for all-cause mortality of the intermediate group was 1.17 (95% confidence interval [CI], 0.98 to 1.40) for men and 1.27 (95% CI, 1.01 to 1.61) for women, and the corresponding values for the high-CRP group were 1.98 (95% CI, 1.61 to 2.42) for men and 1.41 (95% CI, 1.03 to 1.95) for women. Similar trends were found for CRP evaluated as a continuous variable and for cardiovascular mortality. Conclusions: Higher CRP concentrations were associated with higher mortality in a rural Korean population, and this association was more prominent in men than in women.

• Journal of Korean Neurosurgical Society
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• 제58권4호
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• pp.368-372
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• 2015

Objective : The occurrence of acute cerebral infection following deep brain stimulation (DBS) is currently being reported with elevation of C-reactive protein (CRP) level. The aim of the present study was to establish normal range of the magnitude and time-course of CRP increases following routine DBS procedures in the absence of clinical and laboratory signs of infection. Methods : A retrospective evaluation of serial changes of plasma CRP levels in 46 patients undergoing bilateral, two-staged DBS was performed. Because DBS was performed as a two-staged procedure involving; implantation of lead and internal pulse generator (IPG), CRP was measured preoperatively and postoperatively every 2 days until normalization of CRP (post-lead implantation day 2 and 4, post-IPG implantation day 2, 4, and 6). Results : Compared with preoperative CRP levels ($0.12{\pm}0.17mg/dL$, n=46), mean CRP levels were significantly elevated after lead insertion day 2 and 4 ($1.68{\pm}1.83mg/dL$, n=46 and $0.76{\pm}0.38mg/dL$, n=16, respectively, p<0.001). The mean CRP levels at post-lead implantation day 2 were further elevated at post-IPG implantation day 2 ($3.41{\pm}2.56mg/dL$, n=46, respectively, p<0.01). This elevation in post-IPG day 2 rapidly declined in day 4 ($1.24{\pm}1.29mg/dL$, n=46, p<0.05) and normalized to preoperative value at day 6 ($0.42{\pm}0.33mg/dL$, n=46, p>0.05). Mean CRP levels after IPG implantation were significantly higher in patients whose IPGs were implanted at post-lead day 3 than those at post-lead day 5-6 ($3.99{\pm}2.80mg/dL$, n=30, and $2.31{\pm}1.56mg/dL$, n=16, respectively, p<0.05). However, there was no difference in post-IPG day 2 and 4 between them (p>0.05). Conclusion : The mean postoperative CRP levels were highest on post-IPG insertion day 2 and decreased rapidly, returning to the normal range on post-IPG implantation day 6. The duration of post-lead implantation period influenced the magnitude of CRP elevation at post-IPG insertion day 2. Information about the normal response of CRP following DBS could help to avoid unnecessary diagnostic and therapeutic efforts.

• 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.

• Journal of Korean Neurosurgical Society
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• 제56권3호
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• pp.218-223
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• 2014

Objective : C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are often utilized to evaluate for postoperative infection. Abnormal values may be detected after surgery even in case of non-infection because of muscle injury, transfusion, which disturbed prompt perioperative management. The purpose of this study was to evaluate and compare the perioperative CRP, ESR, and white blood cell (WBC) counts after spine surgery, which was proved to be non-infection. Methods : Twenty patients of lumbar open discectomy (LOD) and 20 patients of posterior lumbar interbody fusion (PLIF) were enrolled in this study. Preoperative and postoperative prophylactic antibiotics were administered routinely for 7 days. Blood samples were obtained one day before surgery and postoperative day (POD) 1, POD3, and POD7. Using repeated measures ANOVA, changes in effect measures over time and between groups over time were assessed. All data analysis was conducted using SAS v.9.1. Results : Changes in CRP, within treatment groups over time and between treatment groups over time were both statistically significant F(3,120)=5.05, p=0.003 and F(1,39)=7.46, p=0.01, respectively. Most dramatic changes were decreases in the LOD group on POD3 and POD7. Changes in ESR, within treatment groups over time and between treatment groups over time were also found to be statistically significant, F(3,120)=6.67, p=0.0003 and F(1,39)=3.99, p=0.01, respectively. Changes in WBC values also were be statistically significant within groups over time, F(3,120)=40.52, p<0.001, however, no significant difference was found in between groups WBC levels over time, F(1,39)=0.02, p=0.89. Conclusion : We found that, dramatic decrease of CRP was detected on POD3 and POD7 in LOD group of non-infection and dramatic increase of ESR on POD3 and POD7 in PLIF group of non-infection. We also assumed that CRP would be more effective and sensitive parameter especially in LOD than PLIF for early detection of infectious complications. Awareness of the typical pattern of CRP, ESR, and WBC may help to evaluate the early postoperative course.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제49권5호
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• pp.252-261
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• 2023

Objectives: Patients undergoing oral surgery exhibit high anxiety, which may elevate their cortisol levels and affect postoperative recovery. Overweight patients are often encountered in the dental clinic due to the increasing prevalence of overweight. We aimed to investigate the relationships between preoperatively assessed body mass index (BMI), serum cortisol and high-sensitivity C-reactive protein (hs-CRP) levels, and visual analog scale (VAS) scores and preoperative anxiety in patients undergoing mandibular third molar (MM3) extraction and to identify predictors of postoperative complications. Patients and Methods: We analyzed 43 patients (age, 20-42 years) undergoing MM3 extraction. At the first visit, patients completed the Modified Dental Anxiety Scale (MDAS) and Amsterdam Preoperative Anxiety and Information Scale (APAIS) questionnaires. Their BMI and VAS scores were also calculated. The participants underwent blood tests 1 hour before MM3 extraction. On the first postoperative day, the participants' VAS scores and serum hs-CRP levels were reevaluated. Results: We found that BMI was significantly correlated with preoperative VAS scores. Further, BMI and preoperative hs-CRP levels were significantly correlated among women and patients undergoing extractions of fully impacted MM3s. No correlations were found between serum cortisol and other variables. The preoperative MDAS and VAS scores were significantly positively correlated, especially among patients undergoing extractions of fully impacted MM3s. Multiple linear regression showed that BMI and the eruption status of the MM3 were significant predictors of postoperative hsCRP levels and VAS scores, respectively. Conclusion: In MM3 removals, patients with higher BMI showed elevated hs-CRP and higher VAS scores before surgery. Patients with higher anxiety among those undergoing extractions of fully impacted MM3s showed higher preoperative VAS scores. The two main predictors of postoperative complications were BMI and MM3 eruption status.

• Annals of Occupational and Environmental Medicine
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• 제35권
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• pp.38.1-38.10
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• 2023

Background: Hearing loss (HL) is linked to an elevated risk of cardiovascular diseases (CVDs). The pathogeneses of HL and CVD commonly involve inflammatory responses. Previous studies investigated elevated levels of inflammatory biomarkers in subjects with HL, however, their findings did not demonstrate statistical significance. In our cross-sectional and longitudinal study, we investigated the correlation between HL and increased high-sensitivity C-reactive protein (hsCRP) levels to determine how HL is associated with CVDs. Methods: We conducted a cross-sectional study with workers aged over 18 years who underwent health check-ups at our institution between 2012 and 2018 (n = 566,507), followed by conducting a longitudinal study of workers aged > 18 who underwent health checkups at least twice at our institution between 2012 and 2018 (n = 173,794). The definition of HL was as an average threshold of ≥ 20 dB in pure-tone air conduction at 0.5, 1.0, and 2.0 kHz in both ears. The incidence of increased hsCRP levels throughout the follow-up period was defined as a level exceeding 3 mg/L. Logistic regression and generalized estimating equations were performed to estimate the risk of increased hsCRP levels according to the occurrence of HL in groups stratified by age. Results: In the cross-sectional study, the multivariate-adjusted odds ratio (OR) was 1.17 (95% confidence interval [CI]: 1.02-1.34); the OR was 0.99 (95% CI: 0.80-1.22) in those under 40 and 1.28 (1.08-1.53) in those over 40. In the longitudinal study, the multivariable-adjusted OR was 1.05 (95% CI: 0.92-1.19); the OR was 1.10 (95% CI: 0.90-1.35) in those under 40 and 1.20 (1.01-1.43) in those over 40. Conclusions: This cross-sectional and longitudinal study identified an association between HL and increased hsCRP levels in workers aged over 40 years.

• Journal of Periodontal and Implant Science
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• 제45권3호
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• pp.101-110
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• 2015

Purpose: Sclerostin, an inhibitor of Wnt/${\beta}$-catenin signaling, exerts negative effects on bone formation and contributes to periodontitis-induced alveolar bone loss. Recent studies have demonstrated that serum sclerostin levels are increased in diabetic patients and that sclerostin expression in alveolar bone is enhanced in a diabetic periodontitis model. However, the molecular mechanism of how sclerostin expression is enhanced in diabetic patients remains elusive. Therefore, in this study, the effect of hyperglycemia on the expression of sclerostin in osteoblast lineage cells was examined. Methods: C2C12 and MLO-Y4 cells were used in this study. In order to examine the effect of hyperglycemia, the glucose concentration in the culture medium was adjusted to a range of levels between 40 and 100 mM. Gene expression levels were examined by quantitative reverse transcription-polymerase chain reaction and Western blot assays. Top-Flash reporter was used to examine the transcriptional activity of the ${\beta}$-catenin/lymphoid enhanced factor/T-cell factor complex. Tumor necrosis factor-alpha ($TNF{\alpha}$) protein levels were examined with the enzyme-linked immunosorbent assay. The effect of reactive oxygen species on sclerostin expression was examined by treating cells with 1 mM $H_2O_2$ or 20 mM N-acetylcysteine. Results: The high glucose treatment increased the mRNA and protein levels of sclerostin. High glucose suppressed Wnt3a-induced Top-Flash reporter activity and the expression levels of osteoblast marker genes. High glucose increased reactive oxygen species production and $TNF{\alpha}$ expression levels. Treatment of cells with $H_2O_2$ also enhanced the expression levels of $TNF{\alpha}$ and sclerostin. In addition, N-acetylcysteine treatment or knockdown of $TNF{\alpha}$ attenuated high glucose-induced sclerostin expression. Conclusions: These results suggest that hyperglycemia increases sclerostin expression via the enhanced production of reactive oxygen species and $TNF{\alpha}$.