• Journal of Ginseng Research
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• v.38 no.2
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• pp.83-88
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• 2014

The adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of cellular energy. Once activated, it switches on catabolic pathways generating adenosine triphosphate (ATP), while switching off biosynthetic pathways consuming ATP. Pharmacological activation of AMPK by metformin holds a therapeutic potential to reverse metabolic abnormalities such as type 2 diabetes and nonalcoholic fatty liver disease. In addition, altered metabolism of tumor cells is widely recognized and AMPK is a potential target for cancer prevention and/or treatment. Panax ginseng is known to be useful for treatment and/or prevention of cancer and metabolic diseases including diabetes, hyperlipidemia, and obesity. In this review, we discuss the ginseng extracts and ginsenosides that activate AMPK, we clarify the various mechanisms by which they achieve this, and we discuss the evidence that shows that ginseng or ginsenosides might be useful in the treatment and/or prevention of metabolic diseases and cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.595-600
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• 2015

Background: Accumulating evidence suggests that metformin possesses anticarcinogenic properties, and its use is associated with favorable outcomes in several cancers. However, it remains unclear whether metformin influences prognosis in prostate cancer (PCa) with concurrent type 2 diabetes (T2D). Materials and Methods: We searched PubMed, EMBASE, and the Cochrane Library from database inception to April 16, 2014 without language restrictions to identify studies investigating the effect of metformin treatment on outcomes of PCa with concurrent T2D. We conducted a meta-analysis to quantify the risk of recurrence, progression, cancer-specific mortality, and all-cause mortality. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Publication bias was assessed by Begg's rank correlation test. Results: A total of eight studies fulfilled the eligibility criteria. We found that diabetic PCa patients who did not use metformin were at increased risk of cancer recurrence (RR, 1.20; 95%CI, 1.00-1.44), compared with those who used metformin. A similar trend was observed for other outcomes, but their relationships did not reach statistical significance. Funnel plot asymmetry was not observed among studies reporting recurrence (p=0.086). Conclusions: Our results suggest that metformin may improve outcomes in PCa patients with concurrent T2D. Well-designed large studies and collaborative basic research are warranted.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.1
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• pp.19-48
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• 2008

In order to verify the risk of onset of the illnesses based on gender, age, and monthly income 1,739 subjects from Hongcheon county, Gangwon province were selected. Questionnaire on demographic sociology, health condition, existence of illnesses(cancer, hypertension, stroke, diabetes, arthritis, cardiac disorders), and usage of public health services was surveyed from October 1, 2006 to October 20, 2006. Following conclusions were reached on the basis of the questionnaire : - For demographic sociological peculiarities, gender, age, occupation, and education level were evenly distributed. Most were under normal marriage(67.38%), health insurance(86.39%), 494(36.0%) individuals with less than monthly income of 1 million won, 494(36.0%) individuals with monthly income between 1 and 2 million won, 219(16.0%) with monthly income between 2 and 3 million won, and 164(12.0%) individuals with more than 3 million won, thus showing relatively low income. - For health status, 1,199(70.28%) individuals are non-smokers, 209(45.63%) individuals smoke $10{\sim}20$ cigarettes a day, 754(44.02%) individuals exercise less than twice a week are the major sector of the population. 1,518(88.10%) individuals have regular checkup more than once and 1,131(65.49%) stated their health condition less than average. - For comparison of existence of illnesses between genders, there was no statistical significance on cancer, stroke, and diabetes. But statistical significance was shown on hypertension(P value 0.025), arthritis(P value 0.000), and cardiac disorders(P value 0.016). Statistical significance was seen in the age comparison, and OR(confidence interval) drastically increased with increase in age. - There was no difference between the primary health clinic(P value 0.000), most visited clinic(P value 0.000), selection criteria(P value 0.000), and satisfaction on efficacy(P value 0.000). There was a tendency preferring hospital than public health center with increase in income. - For correlation between the existence of illnesses among different income levels, except for cancer(P value 0.172), statistical significance was seen in hypertension(P value 0.000), stroke(P value 0.003), diabetes (P value 0.001), arthritis(P value 0.000), and cardiac disorders(P value 0.000). The number of individuals suffering from illnesses and ratio all decreased for all illnesses with increase in income. - After adjusting confounding factors(gender, age, income, marriage, occupation, education) and male (1) as the standard, OR (confidence interval) of cancer, hypertension, stroke, diabetes, arthritis, cardiac disorders were 0.47(0.11${\sim}$2.05), 1.27(0.89${\sim}$1.81), 0.58(0.21${\sim}$1.59), 0.71(0.41${\sim}$1.23), 1.79(1.34${\sim}$2.39, P<0.01), and 1.46(0.72${\sim}$2.96), respectively. Risk of arthritis is significantly high in female and 20's (1) as the standard, OR(confidence interval) of cancer, hypertension, stroke, diabetes, arthritis, cardiac disorders were 1.01(0.96${\sim}$1.07), 1.06(1.04${\sim}$1.07, P<0.01), 1.05(1.01${\sim}$1.10, P<0.01), 1.06(1.03${\sim}$1.08, P<0.01), 1.05(1.03${\sim}$1.06, P<0.01), and 1.06(1.04${\sim}$1.09, P<0.01), respectively. Risk of onset for illnesses significantly increased with yearly aging except for cancer. - For comparison between monthly income after adjusting confounding factors(gender, age, income, marriage, occupation, education), with less than 1 million won (1) as the standard, OR(confidence interval) of cancer for 1 to 2 million won, 2 to 3 million won, and more than 3 million won were 0.23(0.03${\sim}$2.16), 2.53(0.41${\sim}$15.43), and 1.73(0.15${\sim}$19.50), respectively. OR(confidence interval) of hypertension were 1.12(0.76 ${\sim}$1.66), 0.68(0.34${\sim}$1.34), and 2.04(1.08${\sim}$3.86, P<0.01), respectively. OR(confidence interval) of stroke were 0.96(0.30${\sim}$3.08) for 1 to 2 million won, and 0.80(0.08${\sim}$8.46) for 2 to 3 million won. OR(confidence interval) of diabetes were 0.73(0.38${\sim}$1.38), 0.65(0.24${\sim}$1.71), and 0.69(0.24${\sim}$2.01), respectively. The values were 0.76(0.55${\sim}$1.03), 1.14(0.75${\sim}$1.73), and 0.90(0.56${\sim}$1.46), respectively for arthritis. OR(confidence interval) of cardiac disorders were 1.15(0.53${\sim}$2.48), 0.63(0.13${\sim}$3.12), and 1.20(0.28${\sim}$5.14), respectively. Risks of cancer, hypertension, stroke, diabetes, arthritis, and cardiac disorders were dependent of monthly income, and stroke and diabetes decreased with increase in income. Summarizing above data, arthritis was significantly higher in women and increase in age by each year brought significant increase in the chance of onset in hypertension, stroke, diabetes, arthritis, and cardiac disorders except for cancer. Stroke and diabetes decreased with increase in income. Above findings can be applied and reflected in public health policies at the national level, and it can also be applied at the personal level for individual health maintenance and prevention.

• Journal of Preventive Medicine and Public Health
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• v.45 no.6
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• pp.394-401
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• 2012

Objectives: Diabetes and obesity each increases mortality, but recent papers have shown that lean Asian persons were at greater risk for mortality than were obese persons. The objective of this study is to determine whether an interaction exists between body mass index (BMI) and diabetes, which can modify the risk of death by cardiovascular disease (CVD). Methods: Subjects who were over 20 years of age, and who had information regarding BMI, past history of diabetes, and fasting blood glucose levels (n=16 048), were selected from the Korea Multi-center Cancer Cohort study participants. By 2008, a total of 1290 participants had died; 251 and 155 had died of CVD and stroke, respectively. The hazard for deaths was calculated with hazard ratio (HR) and 95% confidence interval (95% CI) by Cox proportional hazard model. Results: Compared with the normal population, patients with diabetes were at higher risk for CVD and stroke deaths (HR, 1.84; 95% CI, 1.33 to 2.56; HR, 1.82; 95% CI, 1.20 to 2.76; respectively). Relative to subjects with no diabetes and normal BMI (21 to 22.9 $kg/m^2$), lean subjects with diabetes (BMI <21 $kg/m^2$) had a greater risk for CVD and stroke deaths (HR, 2.83; 95% CI, 1.57 to 5.09; HR, 3.27; 95% CI, 1.58 to 6.76; respectively), while obese subjects with diabetes (BMI ${\geq}25kg/m^2$) had no increased death risk (p-interaction <0.05). This pattern was consistent in sub-populations with no incidence of hypertension. Conclusions: This study suggests that diabetes in lean people is more critical to CVD deaths than it is in obese people.

• Journal of Microbiology and Biotechnology
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• v.25 no.7
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• pp.1047-1055
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• 2015

For the search of a potent first-in-class compound to inactivate macrophages responsible for inflammatory responses, in the present study, we investigated the anti-nflammatory effects of YH-1118, a novel synthetic compound, in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line, Raw 264.7. YH-1118 inhibited LPS-induced nitric oxide (NO) production and inducible NO synthase (iNOS) expression at both the protein and mRNA levels. The suppression of LPS-induced iNOS expression by YH-1118 was mediated via nuclear factor kappa B (NF-κB), but not activator protein-1 (AP-1) transcription factor. This was supported by the finding that YH-1118 attenuated the phosphorylation of inhibitor of κBα (IκBα) and nuclear translocation and DNA binding activity of NF-κB. Through the mechanisms that YH-1118 inhibited the activation of IκB kinases (IKKs), upstream activators of NF-κB, or p38 MAPK, YH-1118 significantly suppressed LPS-induced production of pro-inflammatory cytokines, tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 (p < 0.05). In conclusion, our results suggest that YH-1118 inhibits LPS-induced inflammatory responses by blocking IKK and NF-κB activation in macrophages, and may be a therapeutic candidate for the treatment of various inflammatory diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.11001-11001
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• 2015

• Journal of Preventive Medicine and Public Health
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• v.49 no.1
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• pp.45-52
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• 2016

Objectives: Previous large-scale cohort studies conducted in Korea have found a positive association between diabetes mellitus (DM) and colorectal cancer (CRC) in men only, in contrast to studies of other populations that have found significant associations in both men and women. Methods: A total of 1070 CRC cases and 2775 controls were recruited from the National Cancer Center, Korea between August 2010 and June 2013. Self-reported DM history and the duration of DM were compared between cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by binary and polytomous logistic regression models. Results: DM was associated with an elevated risk of CRC in both men (OR, 1.47; 95% CI, 1.13 to 1.90) and women (OR, 1.92; 95% CI, 1.24 to 2.98). This association remained when we controlled for age, body mass index, alcohol consumption, and physical activity level. In sub-site analyses, DM was associated with distal colon cancer risk in both men (multivariate OR, 2.04; 95% CI, 1.39 to 3.00) and women (multivariate ORs, 1.99; 95% CI, 1.05 to 3.79), while DM was only associated with rectal cancer risk in women (multivariate OR, 2.05; 95% CI, 1.10 to 3.82). No significant association was found between DM and proximal colon cancer risk in either men (multivariate OR, 1.45; 95% CI, 0.88 to 2.41) or women (multivariate OR, 1.79; 95% CI, 0.78 to 4.08). Conclusions: Overall, DM was associated with an increased risk of CRC in Koreans. However, potential over-estimation of the ORs should be considered due to potential biases from the case-control design.

• Mass Spectrometry Letters
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• v.4 no.2
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• pp.25-29
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• 2013

Proteomics for biomarker validation needs high throughput instrumentation to analyze huge set of clinical samples for quantitative and reproducible analysis at a minimum time without manual experimental errors. Sample preparation, a vital step in proteomics plays a major role in identification and quantification of proteins from biological samples. Tryptic digestion a major check point in sample preparation for mass spectrometry based proteomics needs to be more accurate with rapid processing time. The present study focuses on establishing a high throughput automated online system for proteolytic digestion and desalting of proteins from biological samples quantitatively and qualitatively in a reproducible manner. The present study compares online protein digestion and desalting of BSA with conventional off-line (in-solution) method and validated for real time sample for reproducibility. Proteins were identified using SEQUEST data base search engine and the data were quantified using IDEALQ software. The present study shows that the online system capable of handling high throughput samples in 96 well formats carries out protein digestion and peptide desalting efficiently in a reproducible and quantitative manner. Label free quantification showed clear increase of peptide quantities with increase in concentration with much linearity compared to off line method. Hence we would like to suggest that inclusion of this online system in proteomic pipeline will be effective in quantification of proteins in comparative proteomics were the quantification is really very crucial.

• Mass Spectrometry Letters
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• v.3 no.2
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• pp.39-42
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• 2012

Phosphorylation and glycosylation are two of the most important and widespread post-translational modifications (PTMs) in an organism. Proteomics analysis of the PTMs has been challenged by low stoichiometry of the modified proteins and suppression effects by high abundance proteins, typically no-functional house-keeping proteins. In this study, a novel method was applied for not only isolating PTM peptides from intact peptides but also concurrently characterizing of glyco- and phosphoproteome using electrostatic repulsion hydrophilic interaction chromatography (ERLIC) packed with silica coated by crosslinked polyethyleneimine. For 2 mg tryptic digest of mouse proteome of epicardial adipose tissue with fat diet, 802 N-glycosylated peptides of 316 glycoproteins and 159 phosphorylated peptides of 75 phosphoproteins were identified using HPLC chip/quadrupole time-of-flight (Q-OF) tandem mass spectrometer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4265-4269
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• 2014

Purpose: This study aimed at summarizing epidemiological evidence of the association between gestational diabetes mellitus (GDM) and subsequent risk of cancer. Materials and Methods: We searched Medline, Embase, Cancer Lit and CINAHL for epidemiological studies published by February 1, 2014 examining the risk of cancer in patients with history of GDM using highly inclusive algorithms. Information about first author, year of publication, country of study, study design, cancer sites, sample sizes, attained age of subjects and methods used for determining GDM status were extracted by two researchers and Stata version 11.0 was used to perform the meta-analysis and estimate the pooled effects. Results: A total of 9 articles documented 5 cohort and 4 case-control studies containing 10,630 cancer cases and 14,608 women with a history of GDM were included in this review. Taken together, the pooled odds ratio (OR) between GDM and breast cancer risk was 1.01 (0.87-1.17); yet the same pooled ORs of case-control and cohort studies were 0.87 (0.71-1.06) and 1.25 (1.00-1.56) respectively. There are indications that GDM is strongly associated with higher risk of pancreatic cancer (HR=8.68) and hematologic malignancies (HR=4.53), but no relationships were detected between GDM and other types of cancer. Conclusions: Although GDM increases the risk of certain types of cancer, these results should be interpreted with caution becuase of some methodological flaws. The issue merits added investigation and coordinated efforts between researchers, antenatal clinics and cancer treatment and registration agencies to help attain better understanding.