• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5687-5692
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• 2013

Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer development over the past decades. However, the mechanism underlying this contribution is poorly understood. In this study, we determined that high glucose enhanced proteasome activity was accompanied by enhanced proliferation, migration and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7 cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose-induced MCF-7 cell growth and invasion. Furthermore, high glucose increased protein kinase C delta ($PKC{\delta}$)-phosphorylation. Administration of the specific $PKC{\delta}$ inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, $PKC{\delta}$ inhibition by both rottlerin and $PKC{\delta}$ shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that $PKC{\delta}$-dependent ubiquitin proteasome system activation plays an important role in high glucose-induced breast cancer cell growth and metastasis.

• Development and Reproduction
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• v.22 no.2
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• pp.133-142
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• 2018

Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.

• Health Policy and Management
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• v.21 no.1
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• pp.23-43
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• 2011

Access to health care is complicated to define. It is a multidimensional process. In addition to the matters of quality of care, geographical accessibility and availability of the right type of care, finance, and acceptability are all involved. The purposes of this paper are to measure the geographic distances between patient residency locations and health service organizations in which the patients hadvisited, and to investigate the association between geographical distance measures and variables involved in health service utilization. The study used the first and the second wave of the 2008 Korea Health Panel Survey. The samples of analyses were patients who had visited outpatient or used ambulatory health services, and the total observations (visit numbers) analyzed were 229,128. We divided the samples into a frequent-visit illness group (Group 1) and a non-frequent visit illness group (Group 2) based on over 5,000 total visit numbers. We exploited three level analyses using xtmixed of STATA${\Box}$ 11.1 command with/without interaction terms among age, sex, and occupation. Geographical distances were measured using the Haversine method. Group 1 was tended to older and lower equivalent income than those of Group 2, but the geographic difference were not observed in terms of area deprivation index and standard mortality ratios. Amongst group 1, diabetes mellitus patients travelled far to visit health care organizations, and arthritis patients were more deprived in terms of the personal and areal characteristics. The study revealed that residents in rural areas traveled about 10 times more long distances than those whom lived in larger cities after adjusting for various variables, which we used for analyses. This study contributed to the practical understanding of health service utilizations using empirical analyses, and found that the types of diseases and socioeconomic characteristics of patients tended to define the amount of travel distance to healthcare organizations.

• Journal of Preventive Medicine and Public Health
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• v.53 no.2
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• pp.98-105
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• 2020

Objectives: Obesity is regarded as one of the most prominent health threats worldwide and a serious risk factor for non-communicable diseases, such as diabetes mellitus type 2, high blood pressure, cardiovascular diseases, and some types of cancer. Given the role that societal development-as reflected by the Human Development Index (HDI)-may play in the prevalence of obesity and overweight, this study aimed to investigate the degree to which the prevalence of obesity and overweight is affected by HDI and its components. Methods: In this ecological study, the required data on HDI and its components were gathered from the latest report of the United Nations Development Program, and data on obesity and overweight were acquired from the latest reports published on the World Health Organization website. Statistical analyses were conducted using SPSS version 24.0. Results: The prevalence of obesity was determined to be significantly higher among females than males, and the gross national index per capita was found to be significantly higher for males than females (p<0.05). Significant positive correlations were found between HDI and its components and sex, as well as indices of obesity and overweight. Conclusions: A significant positive correlation exists between HDI and obesity. As policy-makers attempt to improve the general welfare of the people, they should be aware of potential unwanted effects of development on the risk of obesity and overweight among the population.

• Advances in Traditional Medicine
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• v.5 no.3
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• pp.201-208
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• 2005

Earlier we have reported the antidiabetic activity of fresh juice of rhizomes of Zingiber officinale (Z. officinale) and its correlation with 5-HT receptor antagonism. Since 6-gingerol the marker compound of Z. officinale is reported to posses 5-HT anatgonistic activity, the present investigation, was undertaken to find out the concentration of 6-gingerol present in methanolic extract of Z. officinale and its different fractions (petroleum ether, toluene and chloroform). We also evaluated these fractions for antidiabetic activity in streptozotocin (STZ)-induced neonatal type 2 diabetic rats. Fasting glucose and insulin levels in non insulin dependent diabetes mellitus (NIDDM) rats were found to be significantly (P < 0.05) higher than control rats and these were significantly decreased by treatment with methanolic extract of Z. officinale and its fractions. The results of oral glucose tolerance test (OGTT) showed that methanolic extract and its fractions significantly (P < 0.05) decreased both STZ-induced increase in $AUC_{glucose}$ and $AUC_{insulin}$ values in NIDDM groups. Treatment with petroleum ether fraction produced a greater reduction in elevated glucose and $AUC_{glucose}$ levels as compared to treatment with other fractions. Treatment with methanolic extract of Z. officinale and its fractions also produced significant reduction in the elevated lipid, serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) levels in NIDDM rats. The effect of petroleum ether fraction on elevated lipid, SGOT and SGPT levels was significantly greater as compared to treatment with other fractions. The concentration of 6-gingerol was found to be maximum in petroleum ether fraction (11.430%) and minimum in chloroform fraction (0.973%). The methanolic extract and toluene fraction was found to contain 3.080% and 2.191 %, 6-gingerol respectively. In conclusion, our data suggest that methonolic extract and its fractions possess significant antidiabetic activity in NIDDM rats. The extent of activity appears to be dependent on the concentration of 6-gingerol present in the extract or its fractions.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.357-362
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• 2010

To enhance therapeutic effects of insulin-sensitizing adipokine, ADN gene and potent agonists, rosiglitazone for the $PPAR{\gamma}$, cationic liposomes as non-viral vectors were formulated. The particle size and zeta potential of drug loaded and unloaded cationic liposomes were investigated. The complex formation between cationic liposomes and negatively charged plasmid DNA was confirmed and the protection from DNase was observed. In vitro transfection was investigated in HepG2, HeLa, and HEK293 cells by mRNA expression of ADN. Encapsulation efficacy of rosiglitazone-loaded liposomes was determined by UV detection. Particle sizes of cationic liposomes were in the range of 110-170 nm and those of rosiglitazone-loaded cationic liposomes were in the range of 130-180 nm, respectively. Gel retardation of complexes indicated that the complex was formed at weight ratios of cationic lipid to plasmid DNA higher than 20:1. Both complexes protected plasmid DNA from DNase either drug free or drug loading. Encapsulation efficiency of rosiglitazone-loaded emulsion was increased by drug dose. The mRNA expression levels of ADN were dose-dependently increased in cells transfected with plasmid DNA. Therefore, cationic liposomes could be potential co-delivery system for drug and gene.

• IMMUNE NETWORK
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• v.11 no.1
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• pp.59-67
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• 2011

Background: Insulin resistance is an integral feature of metabolic syndromes, including obesity, hyperglycemia, and hyperlipidemia. In this study, we evaluated whether the aloe component could reduce obesity-induced inflammation and the occurrence of metabolic disorders such as blood glucose and insulin resistance. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM lowered fasting blood glucose and plasma insulin compared with HFD. Obesity-induced inflammatory cytokine (IL-$1{\beta}$, -6, -12, TNF-${\alpha}$) and chemokine (CX3CL1, CCL5) mRNA and protein were decreased markedly, as was macrophage infiltration and hepatic triglycerides by Aloe QDM. At the same time, Aloe QDM decreased the mRNA and protein of $PPAR{\gamma}/LXR{\alpha}$ and $11{\beta}$-HSD1 both in the liver and WAT. Conclusion: Dietary aloe formula reduces obesity-induced glucose tolerance not only by suppressing inflammatory responses but also by inducing anti-inflammatory cytokines in the WAT and liver, both of which are important peripheral tissues affecting insulin resistance. The effect of Aloe QDM complex in the WAT and liver are related to its dual action on $PPAR{\gamma}$ and $11{\beta}$-HSD1 ression and its use as a nutritional intervention against T2D and obesity-related inflammation is suggested.

• Korean Journal of Clinical Pharmacy
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• v.29 no.4
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• pp.278-285
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• 2019

Background: Rheumatoid arthritis is highly prevalent in overweight patients with type 2 diabetes mellitus and can be reduced by physical activity via altered proinflammatory parameters. However, the association between the frequency of physical activity and the prevalence of rheumatoid arthritis in prediabetic patients remains unclear and was evaluated in this study. Methods: Utilizing the Korean National Health Insurance Sharing Service database, 58,391 adults, who met the research criteria and underwent a general medical check-up between 2009 and 2013, were selected for this study. To analyze the data, a logistic regression with a proc survey logistic procedure was used. Results: The study revealed that the cumulative rheumatoid arthritis prevalence was lower in prediabetic patients compared to that in the control group (OR, 0.64; 95% CI, 0.483-0.840; p=0.001). More frequent physical activity (≥3 days/week) was significantly associated with a reduced rheumatoid arthritis prevalence in both groups (OR, 0.28; 95% CI, 0.039-0.521; p=0.044 vs. OR, 0.15; 95% CI, 0.063-0.237; p=0.007). Additionally, a 3.8-fold higher risk of rheumatoid arthritis development was observed in prediabetic adults with less frequent baseline physical activity (≤2 days/week). Overall, in prediabetes, the prevalence of rheumatoid arthritis was associated with the frequency of physical activity and not with the fasting plasma glucose levels. Conclusion: More frequent physical activity is associated with a low risk of developing rheumatoid arthritis in prediabetic patients. Thus, further studies are needed to confirm the clinical outcomes of frequent physical activity in rheumatoid arthritis prevention and control.

• Journal of Preventive Medicine and Public Health
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• v.49 no.3
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• pp.143-152
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• 2016

Objectives: Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. Methods: We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. Results: A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non-significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. Conclusions: The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high-risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women.

• Journal of Home Health Care Nursing
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• v.28 no.2
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• pp.178-185
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• 2021

Purpose: In this study, we aimed to explore the risk factors for catheter-associated urinary tract infections (CAUTI) in patients receiving home care nursing. Methods: A total of 117 participants registered for home care nursing provided by the University of C hospital in Seoul were included in the study. Data were based on a survey and urine examination results from June to July 2018. Results: Asymptomatic bacteriuria was identified in 96 (82%) patients. Age, sex, activity, diabetes mellitus, mental status, presence of other diseases, catheter material type, catheter size and fixation, hand washing (care giver), gloving (care giver), perineal care, and bladder irrigation were not recognized as risk factors for CAUTI. Age and catheterization duration were associated with CAUTI. Conclusions: Old age was found to be a risk factor for CAUTI (p=0.048). CAUTI incidence decreased as catheter use exceeded 70 months (p=0.028).