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Inhye Kim,1,* Young Ho Song,2,* Nem Singh,2 Yong Joon Jeong,3 Jung Eun Kwon,3 Hyunuk Kim,4 Young Mi Cho,3 Se Chan Kang,3 Ki-Whan Chi2 1Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, 2Department of Chemistry, University of Ulsan, Ulsan, 3Department of Life Science, Gachon University, Seongnam, 4Energy Materials Lab, Korea Institute of Energy Research, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3,6-bis(pyridin-3-ylethynyl)phenanthrene (bpep) (1) and one of the three dinuclear arene ruthenium clips, [(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)][OTf]2 (OO\OO =2,5-dioxido-1,4-benzoquinonato, OTf = triflate) (2), 5,8-dioxido-1,4-naphthoquinonato (3), or 6,11-dioxido-5,12-naphthacenediona (4), resulted in three molecular bowls 5–7 of general formula [{(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)}2(bpep)2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization–mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5–7 were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study. Keywords: phenanthrene, ruthenium, coordination self-assembly, gastric cancer, Akt/mTOR

This study evaluated the efficacy of Web-based diabetes self-management education for newly diagnosed patients with type II diabetes as an alternative to group lectures. Using a non-equivalent control group, pretest-post-test design, the participants in the Web group (n = 15) took part in a Web-based diabetes self-management program, while those in the lecture group (n = 16) attended 3 h of group lectures provided by health-care professionals specializing in diabetes care. The outcome variables were measured at the baseline (T0), and 6 weeks (T1) and 3 months (T2) after the interventions. The glycosylated hemoglobin (HbA1c) percentage and diabetes care knowledge in the Web group improved significantly from T0 to T1, while the diabetes care behavior improved significantly from T0 to T1 and from T1 to T2. The diabetes care knowledge and diabetes care behavior in the lecture group improved significantly from T0 to T1, but the HbA1c percentage did not change significantly between any times. These results show the potential of the Web-based program as an alternative to group lectures for diabetes self-management education. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the frequency of recurrent gestational diabetes mellitus (GDM) and to find risk factors that can predict the recurrence of GDM in Korean women with previous GDM.Research Design and Methods: We evaluated women who had GDM in an index pregnancy (1993-2001) and a subsequent pregnancy by 2003. An oral glucose tolerance test (OGTT) was performed during the index pregnancy and 2 months postpartum. The recurrence rate of GDM was assessed among 111 women who had a subsequent pregnancy. Multivariate logistic regression analysis was used to identify independent predictors of recurrent GDM.Results: The frequency of recurrent GDM in subsequent pregnancies was 45.0% (95% CI 35.6-54.4%). Women with impaired fasting glucose and/or impaired glucose tolerance 2 months postpartum were at increased risk for recurrent GDM (relative risk 2.31, 95% CI 1.24-4.30). Higher BMI before the subsequent pregnancy (P = 0.024), higher fasting glucose concentration (P = 0.007) 2 months postpartum, and lower 1-h insulin concentration (P = 0.004) of the diagnostic OGTT in the index pregnancy were independent risk factors for recurrence of GDM in subsequent pregnancies.Conclusions: GDM recurred in nearly half of subsequent pregnancies in Korean women. Fasting glucose 2 months postpartum might be a clinically valuable predictor of recurrent GDM risk. [ABSTRACT FROM AUTHOR]

AIMS: We examined whether the common polymorphisms of the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene are associated with Type 2 diabetes or obesity in the Korean population. METHODS: We genotyped two common PPARgamma polymorphisms (Pro12Ala and 161C > T) and examined their association with the clinical phenotypes found in 684 patients with Type 2 diabetes mellitus and 291 non-diabetic control subjects. RESULTS: The 12Ala allele was less frequent in the Type 2 diabetic patients than in the non-diabetic control subjects (0.036 vs. 0.053, P = 0.024). The allele frequencies of the 161C > T polymorphism did not differ between the control and Type 2 diabetic group (0.158 vs. 0.173). In the non-diabetic controls, those with the T allele had lower BMI and fasting serum triglyceride (TG) concentrations than those with the C/C homozygote (22.7 +/- 2.9 vs. 23.8 +/- 3.2 kg/m2, P = 0.002; 1.45 +/- 0.81 vs. 1.65 +/- 0.83 mmol/l, P = 0.03, respectively). The 12Ala-161T haplotype was associated with a decreased risk for Type 2 diabetes (OR = 0.47, P = 0.009), whereas the 12Pro-161T haplotype was associated with lower BMI and lower fasting serum TG (22.5 +/- 2.8 vs. 23.7 +/- 3.2 kg/m2, P = 0.004; 1.41 +/- 0.87 vs. 1.64 +/- 0.79 mmol/l, P = 0.02, respectively). CONCLUSIONS: The PPARgamma 12Ala allele was associated with a reduced risk of Type 2 diabetes, whereas the PPARgamma 161T allele was associated with lower BMI and fasting serum TG concentrations in the Korean subjects. The subjects with 12Ala-161T haplotypes had a reduced risk of Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Many studies show poor agreement between fasting plasma glucose (FPG)-based and 2-h postchallenge glucose (2-h PG)-based criteria to assess glucose metabolism. We examined the rate of agreement between FPG- and 2-h PG-based criteria in the diagnosis of intermediate hyperglycemia in four representative cohort studies in South Korea and compared the clinical characteristics and biochemical parameters in subjects with impaired fasting glucose (IFG) according to their FPG values. Of 6234 subjects from four population-based studies performed from 1993 to 2000, 4610 individuals with data from a 75g oral glucose tolerance test (OGTT) and no previous history of diabetes were selected. We examined the concordance rate between the FPG and 2-h PG-based criteria. We also investigated the differences in the clinical characteristics and biochemical parameters between individuals with IFG according to their FPG values. The fasting and 2-h PG criteria had large discordance rates in the diagnosis of diabetes and impaired glucose tolerance (IGT) in Korean adults. When individuals with IFG were classified into stage 1 [5.6-6.1mmol/L (100-109mg/dL)] and stage 2 [6.1-7.0mmol/L (110-125mg/dL)] IFG, individuals with stage 2 IFG are more obese and had higher blood pressure and total cholesterol and triglycerides concentrations compared with those with stage 1 IFG. In addition, more individuals with stage 2 IFG were with diabetes as determined by a 2-h PG>or=11.1mmol/L (14.1% vs. 1.9%) (P<0.05). Considering the poorer metabolic profile and higher percentage of people with diabetes by OGTT, these data indicate that, in the Korean population, individuals with stage 2 IFG should be treated differently from those with stage 1 IFG. To detect more cases of diabetes, the OGTT is recommended for all individuals with stage 2 IFG and cases with stage 1 IFG with some additional risk factors for diabetes. [ABSTRACT FROM AUTHOR]