• BMB Reports
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• v.56 no.12
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• pp.663-668
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• 2023

C-reactive protein (CRP) is an inflammatory marker and risk factor for atherosclerosis and cardiovascular diseases. However, the mechanism through which CRP induces myocardial damage remains unclear. This study aimed to determine how CRP damages cardiomyocytes via the change of mitochondrial dynamics and whether survivin, an anti-apoptotic protein, exerts a cardioprotective effect in this process. We treated H9c2 cardiomyocytes with CRP and found increased intracellular ROS production and shortened mitochondrial length. CRP treatment phosphorylated ERK1/2 and promoted increased expression, phosphorylation, and translocation of DRP1, a mitochondrial fission-related protein, from the cytoplasm to the mitochondria. The expression of mitophagy proteins PINK1 and PARK2 was also increased by CRP. YAP, a transcriptional regulator of PINK1 and PARK2, was also increased by CRP. Knockdown of YAP prevented CRP-induced increases in DRP1, PINK1, and PARK2. Furthermore, CRP-induced changes in the expression of DRP1 and increases in YAP, PINK1, and PARK2 were inhibited by ERK1/2 inhibition, suggesting that ERK1/2 signaling is involved in CRP-induced mitochondrial fission. We treated H9c2 cardiomyocytes with a recombinant TAT-survivin protein before CRP treatment, which reduced CRP-induced ROS accumulation and reduced mitochondrial fission. CRP-induced activation of ERK1/2 and increases in the expression and activity of YAP and its downstream mitochondrial proteins were inhibited by TAT-survivin. This study shows that mitochondrial fission occurs during CRP-induced cardiomyocyte damage and that the ERK1/2-YAP axis is involved in this process, and identifies that survivin alters these mechanisms to prevent CRP-induced mitochondrial damage.

• BMB Reports
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• v.46 no.2
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• pp.119-123
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• 2013

Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), an endogenous neurotoxin, is known to perform a role in the pathogenesis of Parkinson's disease (PD). In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with salsolinol. When cytochrome c was incubated with salsolinol, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in salsolinol-treated cytochrome c. Salsolinol also led to the release of iron from cytochrome c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the salsolinol-mediated cytochrome c modification and carbonyl compound formation. It is suggested that oxidative damage of cytochrome c by salsolinol might induce the increase of iron content in cells, subsequently leading to the deleterious condition which was observed. This mechanism may, in part, provide an explanation for the deterioration of organs under neurodegenerative disorders such as PD.

• The Korean Journal of Food And Nutrition
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• v.26 no.4
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• pp.909-918
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• 2013

The objective of this study is to investigate the effects of dietary nutrient intakes for markers of blood glucose and inflammation which is important to the progress of type 2 diabetes and the development of its complications. For this study, 76 adults with diabetes (42 males, 34 females) were recruited from a group of patients who had visited the department of endocrine medicine. Data on anthropometric characteristics, clinical indices such as hemoglobin A1c (HbA1c) and C-reactive protein (CRP), and dietary nutrient intakes were collected. Our results have shown that 66% of subjects were either overweight or obese. Serum analysis indicates that levels of C-peptide, glucose, HbA1c, CRP, triglyceride, LDL-cholesterol were higher than normal range. Results from the dietary nutrient intake survey displayed that intakes of cholesterol and sodium were higher than Dietary Reference Intakes for Koreans. On the contrary, folate intake was lower than the guideline. Within the females, energy contribution from carbohydrate was higher than Korean Diabetes Association guideline. Statistical analysis has revealed a negative correlation between serum HbA1c level and dietary intakes of polyunsaturated fatty acid (PUFA), n-3 PUFA, ${\beta}$-carotene and vitamin E after adjustments for age, BMI, smoking habits, alcohol consumption, exercise and ingestion of diabetes mellitus medication (p<0.05). Serum CRP level was inversely associated with dietary intakes of carbohydrate, protein, vitamin C and fiber (p<0.05). Our results suggest that dietary nutrient intakes may influence the levels of HbA1c and CRP, and subsequently, it may help in the management/treatment of type 2 diabetes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8075-8081
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• 2014

Background: The classical inflammatory biomarker, C-reactive protein (CRP), has been identified to be related to progression of esophageal cancer. Some research showed that elevated pretreatment serum CRP indicated a poor prognosis, but results have been inconsistent. Materials and Methods: We searched the Medline, Embase and the Cochrane Central Search Library for suitable studies and a meta-analysis of eleven (1,886 patients) was conducted to examine the relationship between elevated serum CRP level and overall survival (OS) in esophageal cancer cases. Moreover, correlation analyses were conducted to assess links between pretreatment serum CRP level and tumor node metastasis (TNM) stage as well as T, N, M grade, respectively. Results: The pooled analysis showed that elevated pretreatment serum CRP level was significantly associated with poorer overall survival (HR 2.09, 95%CI 1.52-2.87, p<0.01). Subgroup analyses were conducted by "country", "cut-off value", "treatment" and "number of patients", and no single factor could alter the result. Elevated pretreatment serum CRP was significantly correlated with more advanced TNM stage and T, N, M grade respectively. Conclusions: Elevated pretreatment serum CRP levels are associated with poorer prognosis in esophageal cancer patients, and could serve as a useful biomarker for outcome prediction.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2643-2648
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• 2016

Background: High-sensitivity C-reactive protein (hsCRP) levels are lower in Japanese compared with Western subjects. Since it is uncertain whether hsCRP is a potent predictor of mortality at low CRP concentrations, the present study examined associations with all-cause and cause-specific mortality in a large population of Japanese. Materials and Methods: Subjects were 4,737 men and 6,343 women aged 49-76 years participating in the baseline survey of an ongoing cohort study of lifestyle-related diseases between February 2004 and July 2006. Hazard ratios for all-cause and cause-specific mortality associated with hsCRP levels were estimated using Cox proportional hazards regression. Results: A total of 436 all-cause deaths occurred during a median follow-up of 8 years. The main cause of death was cancer. In men, hsCRP levels were positively associated with the risk of all-cause mortality as well as deaths from cancer and cardiovascular disease (CVD). All-cause mortality hazards for the 2nd (0.34-0.84 mg/L) and the 3rd (${\geq}0.85mg/L$) tertiles of hsCRP were 1.27 (95% confidence interval [CI], 0.93-1.73) and 1.75 (1.30-2.37), respectively (p for trend=0.001). In women, increased risk of all-cause and cause-specific mortality associated with elevated hsCRP levels was observed, but the associations were not statistically significant. Conclusions: HsCRP may be an independent predictor of all-cause, cancer and CVD mortality in apparently healthy Japanese men, but not women. The differential effect of hsCRP in predicting mortality risk by sex warrants further investigation.

• Clinical and Experimental Pediatrics
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• v.61 no.1
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• pp.12-16
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• 2018

Purpose: To differentiate adenoviral pharyngoconjunctival fever (PCF) from acute Kawasaki disease (KD) using laboratory tests before results of virus-real time polymerase chain reaction and ophthalmologic examination are obtained. Methods: Baseline patient characteristics and laboratory measurements were compared between 40 patients with adenovirus infection and 123 patients with KD. Results: The patients with adenovirus infection were generally older than those with KD (median: 3.9 years vs. 2 years, P=0.000). White blood cell and, platelet count, and aspartate aminotransferase, alanine aminotransferase, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels showed significant differences between the 2 groups, but the C-reactive protein (CRP) levels did not ($6.8{\pm}3.0mg/dL$ vs. $8.3{\pm}5.8mg/dL$, P=0.126). In the adenovirus infection group, the CRP levels were <1, <3, <10, and ${\geq}10mg/dL$ in 2 (5%), 3 (7.5%), 30 (75%), and 5 patients (12.5%), respectively. The cutoff NT-proBNP level was 265 pg/mL. Discrepancy was defined as CRP and NT-proBNP levels of ${\geq}3$ or <3 mg/dL, and <265 or ${\geq}265pg/mL$, respectively. Among the 35 patients with adenovirus infection whose CRP levels were ${\geq}3mg/dL$, 29 (82.9%) showed a discrepancy. Conversely, of the 103 patients with KD whose CRP levels were ${\geq}3mg/dL$, 83 (80.6%) showed no discrepancy. Between the groups, a significant difference in discrepancy rate was observed (P=0.000). None of the patients with adenovirus infection had CRP and NT-proBNP levels of <3 mg/dL and ${\geq}265pg/mL$, respectively. Conclusion: With a sensitivity of 82.9% and a specificity of 80.6%, CRP and NT-proBNP levels may differentiate between adenoviral PCF and acute KD.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.243-248
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• 2013

Background: Associations between elevated C-reactive protein (CRP) and cancer risk have been reported for many years, but the results from prospective cohort studies remains controversial. A meta-analysis of prospective cohort studies was therefore conducted to address this issue. Methods: Eligible studies were identified by searching the PubMed and EMBASE up to October 2012. Pooled hazard ratios (HR) was calculated by using random effects model. Results: Eleven prospective cohort studies involving a total of 194,796 participants and 11,459 cancer cases were included in this meta-analysis. The pooled HR per natural log unit change in CRP was 1.105 (95% confidence interval (CI): 1.033-1.178) for all-cancer, 1.308 (95% CI: 1.097-1.519) for lung cancer, 1.040 (95% CI: 0.910-1.170) for breast cancer, 1.063 (95% CI: 0.965-1.161) for prostate cancer, and 1.055 (95% CI: 0.925-1.184) for colorectal cancer. Dose-response analysis showed that the exponentiated linear trend for a change of one natural log unit in CRP was 1.012 (95% CI: 1.006-1.018) for all-cancer. No evidence of publication bias was observed. Conclusions: The results of this meta-analysis showed that the elevated levels of CRP are associated with an increased risk of all-cancer, lung cancer, and possibly breast, prostate and colorectal cancer. The result supports a role of chronic inflammation in carcinogenesis. Further research effort should be performed to identify whether CRP, as a marker of inflammation, has a direct role in carcinogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.42 no.5
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• pp.243-250
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• 2016

Objectives: Many studies have examined histopathological factors and various prognostic scores related to inflammation to predict outcomes. Here, we examined the prognostic value of the C-reactive protein/albumin (CRP/alb) ratio in oral squamous cell carcinoma (OSCC). Materials and Methods: This retrospective study included 40 patients with OSCC. Using univariate and multivariate analyses, we focused on the correlation of the CRP/alb ratio with clinicopathological characteristics and with overall survival. We then compared five inflammation-based prognostic scores, CRP/alb ratio, modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), based on receiver operating characteristic (ROC) curves. Results: The optimal cut-off value for the CRP/alb ratio was 0.085. The group with a high CRP/alb ratio had a high TNM clinical stage (P=0.002) and larger primary tumors (P=0.029), with statistically significant differences in lymph node metastasis and distant metastasis. In addition, when the CRP/alb ratio was high, multivariate analysis showed a lower survival rate (P=0.002; hazard ratio=6.078), and the ROC curve showed more outstanding discriminatory ability regarding overall survival compared to other inflammation-based prognostic scores. Conclusion: The CRP/alb ratio can be an independent prognostic factor when predicting prognosis in OSCC and has good prognostic ability.

• Journal of Sasang Constitutional Medicine
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• v.23 no.4
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• pp.471-486
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• 2011

1. Objectives The purpose of this study was to investigate the high-sensitivity C-reactive protein (hsCRP) related characteristics found in each Sasang Constitutional type. 2. Methods This cross-sectional epidemiological study was conducted using data from 2,842 men and women. After typing each participant into one of the four Sasang constitutional types, they were analyzed on various cardiovascular disease-related variables. 3. Results 1) The predictors of cardiovascular disease (metabolic syndrome, high risk FRS group, high risk hsCRP group) was found to show the highest prevalence in the Taeeum type. 2) In the group with metabolic syndrome, the mean hsCRP concentration in the Taeeum and Soyang types were higher than in the Soeum type. In the group without metabolic syndrome, the mean hsCRP concentration in the Taeeum type were higher than in the Soyang and Soeum types. 3) In the FRS low risk group, the mean hsCRP concentration were higher in order of Taeeum type > Soyang type > Soeum type. In the FRS high risk group, the mean hsCRP concentrations were not significantly different among the Sasang constitutional types. 4. Conclusions The results of this study suggest that the Taeeum constitutional type is a risk factor for high hsCRP and cardiovascular disease. These findings suggest that the prevention of cardiovascular disease is more important in the Taeeum type compared to other constitutional types. Moreover, preventive measures are warranted even in the Taeeum-type persons with low clinical cardiovascular risk.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2089-2094
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• 2014

Background: Although many prognostic factors have been identified for lung cancers, new ones are needed to determine the course of the disease. Recently, a high neutrophil to lymphocyte ratio (NLR) prior to surgery or treatment has been shown to be an indicator of prognosis for cancer. The aim of this study was to investigate the value of NLR as a prognostic factor and the correlation between NLR and other probable clinical prognostic factors in non small cell lung cancer patients prior to treatment. Materials and Methods: Data of patients who were diagnosed with non-small cell lung cancer in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR was calculated before the application of any treatment. Results: A total of 299 patients, 270 (90%) males and 29 (10%) females, were included in the study. Age (p<0.001) stage (p<0.001), Eastern Cooperative Oncology Group performance status (p<0.001), weight loss (p<0.001), anemia (p<0.001), histopatology (p<0.001), NLR ${\geq}3$ (p=0.048), NLR ${\geq}4$ (p=0.025) and NLR ${\geq}5$ (p=0.018) were found to be the prognostic factors. Age, anemia, Eastern Cooperative Oncology Group performance status, the stage, NLR (${\geq}5$) were an independent prognostic factors. There was a positive correlation between NLR and the Eastern Cooperative Oncology Group performance status (0.23, p=0.001), the C reactive protein levels (r=0.36, p<0.001). Conclusions: Prior to treatment high NLR was found as an independent poor prognosis factor. Besides, NLR correlated with Eastern Cooperative Oncology Group performance status and the C reactive protein levels.