• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.525-538
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• 2018

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

• Journal of Preventive Medicine and Public Health
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• v.42 no.2
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• pp.135-142
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• 2009

Objectives : An appropriate sampling strategy for estimating an epidemiologic volume of diabetes has been evaluated through a simulation. Methods : We analyzed about 250 million medical insurance claims data submitted to the Health Insurance Review & Assessment Service with diabetes as principal or subsequent diagnoses, more than or equal to once per year, in 2003. The database was re-constructed to a 'patient-hospital profile' that had 3,676,164 cases, and then to a 'patient profile' that consisted of 2,412,082 observations. The patient profile data was then used to test the validity of a proposed sampling frame and methods of sampling to develop diabetic-related epidemiologic indices. Results : Simulation study showed that a use of a stratified two-stage cluster sampling design with a total sample size of 4,000 will provide an estimate of 57.04%(95% prediction range, 49.83 - 64.24%) for a treatment prescription rate of diabetes. The proposed sampling design consists, at first, stratifying the area of the nation into "metropolitan/city/county" and the types of hospital into "tertiary/secondary/primary/clinic" with a proportion of 5:10:10:75. Hospitals were then randomly selected within the strata as a primary sampling unit, followed by a random selection of patients within the hospitals as a secondly sampling unit. The difference between the estimate and the parameter value was projected to be less than 0.3%. Conclusions : The sampling scheme proposed will be applied to a subsequent nationwide field survey not only for estimating the epidemiologic volume of diabetes but also for assessing the present status of nationwide diabetes control.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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• pp.215-221
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• 2004

To determine the effects of caloric restriction on obese type 2 diabetes we measured body blood glucose and serum lipid level in dietary restricted Otsuka Long Evans Tokushima Fatty (OLETF) rats. OLETF rats (obese diabetic rats) and Long Evans Tokushima Otsuka (LETO) rats (control rats) were grouped into 2 groups; control (free feed) group and 30% caloric restricted (30% CR) group. At 24 weeks of age the 30% CR animals were provided a diet at a level of 30% less food (by weight) than control rats consumed during the previous week. Blood glucose levels and serum triglyceride, total cholesterol, and high density lipoprotein (HDL)-cholesterol levels of CR rats were determined every 2 weeks for 8 weeks total. Blood glucose, triglyceride and total cholesterol levels of OLETF rats were significantly higher compared to LETO rats. In OLETF rats, the blood glucose levels were decreased to 61% by 8 weeks in the 30% CR compared to the non-CR control group, but changes of blood glucose levels were not observed in LETO rats during the 8weeks in the 30% CR. The serum triglyceride levels of OLETF rats were decreased significantly in the 30% CR but no change in the serum of LETO rats was found. The total cholesterol level was not changed by dietary restriction in LETO rats, but significant changes were observed in OLETF rats by 30% dietary restriction. HDL-cholesterol levels were also increased by dietary restriction in both LETO and OLETF rats. These results suggested that elevated blood glucose, triglyceride and total cholesterol levels in diabetes II patients may be reduced by caloric restriction.

• Journal of Biomedical Engineering Research
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• v.23 no.4
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• pp.323-327
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• 2002

Chronic diabetic patients need to sample capillary blood for monitoring and controlling the blood sugar level. Frequent sampling requires to minimize pain during skin puncture. The present study developed mechanisms to minimize pain with effective sampling procedure. which consisted of tapered spring, guiding tunnel, and 30G needle Penetration depth was limited to within 2mm for pain reduction as well as for safety. Simple no-reuse mechanism also prevented the cross-patient and secondary infection possibility. Clinical experiments demonstrated the best convenience and safety with minimal pain in the diabetes, normal, and nursing students groups. Sing1e blood sampling was enough for successful blood sugar test by portable analyzer. The present sing1e use auto-lancet should be of great convenience in frequent capillary blood sampling for the diabetes.

• Journal of Pharmacopuncture
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• v.20 no.3
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• pp.201-206
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• 2017

Objectives: The aim of this study was to investigate the effects of Cassia acutifolia on the obesity and the glucose levels in a rat model of obesity and diabetes. Methods: By random selection, 36 Wistar male rats were divided in two control groups, the positive and the negative control groups, and into four experimental groups receiving different infusions of Cassia acutifolia in water ad libitum. Results: The results revealed a statistically significant anti-obesogenic effect (P = 0.02), although this was not considered clinically significant. Additionally, Cassia acutifolia lowered the glucose levels by 30 mg/dL to 90 mg/dL (P = 0.05). However, we observed adverse effects in the liver, a two-fold increase in transaminase levels (P = 0.002), and in the kidneys, decreased creatinine levels (P = 0.001), and these adverse effects had no viable explanation. Conclusion: Cassia acutifolia has anti-hyperglycemic effects in obese diabetic rats. However, Cassia acutifolia also has adverse effects, so it should not be administered to patients.

• Genomics & Informatics
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• v.7 no.2
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• pp.53-56
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• 2009

Recent evidence has strongly suggested that the CAP/TC10 pathway is involved in the trafficking, docking, and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 to the plasma membrane. However, little is known about how the genes employed in the CAP/TC10 pathway are associated with the development of type 2 diabetes mellitus. In this study, we sequenced 4 genes of the CAP/TC10 pathway [SORBS1, CBL, CRK, and RHOQ] in 24 individuals to identify genetic variations in these loci. A total of 48 sequence variants were identified, including 23 novel variations. To investigate the possible association with type 2 diabetes mellitus, 3 single nucleotide polymorphisms from SORBS1, 3 from CBL, and 4 from RHOQ were genotyped in 1122 Korean type 2 diabetic patients and 1138 nondiabetic controls. Using logistic regression analysis, 1 significant association between SNP rs1376405 in RHOQ and type 2 diabetes mellitus [OR = 8.714 (C.I. 1.714-44.29), p = 0.009] was found in the recessive model. Our data demonstrate a positive association of the RHOQ gene in the CAP/TC10 pathway with T2DM in the Korean population.

• Molecules and Cells
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• v.19 no.1
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• pp.60-66
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• 2005

Low density lipoproteins (LDL) play important roles in the pathogenesis of atherosclerosis. Diabetes is associated with accelerated atherosclerosis leading to cardiovascular disease in diabetic patients. Although LDL stimulates the proliferation of arterial smooth muscle cells (SMC), the mechanisms are not fully understood. We examined the effects of native LDL and glycated LDL on the extracellular signal-regulated kinase (ERK) pathway. Addition of native and glycated LDL to rat aorta SMCs (RASMCs) stimulated ERK phosphorylation. ERK phosphorylation was not affected by exposure to the $Ca^{2+}$ chelator BAPTA-AM but inhibition of protein kinase C (PKC) with GF109203X, inhibition of Src kinase with PP1 ($5{\mu}M$) and inhibition of phospholipase C (PLC) with U73122/U73343 ($5{\mu}M$) all reduced ERK phosphorylation in response to glycated LDL. In addition, pretreatment of the RASMCs with a cell-permeable mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059, $5{\mu}M$) markedly decreased ERK phosphorylation in response to native and glycated LDL. These findings indicate that ERK phosphorylation in response to glycated LDL involves the activation of PKC, PLC, and MEK, but is independent of intracellular $Ca^{2+}$.

• Korean journal of food and cookery science
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• v.32 no.4
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• pp.426-432
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• 2016

Purpose: The consumption of noodles has increased domestically. However, noodles with high carbohydrate content can cause an increase in blood glucose compared with other foods. Therefore, in this study, Naengmyeon with high resistant starch was prepared for decreasing blood glucose by the addition of 0.5% citric acid (CN), 1% guar gum (GN) or 0.5% citric acid and 1% guar gum (CGN), and then it was incubated in a refrigerator for 3 days, and stored in a freezer for 1 month. Methods: The quality characteristics of these Naengmyeon noodles was evaluated based on total starch, resistant starch, water absorption, cooking loss, turbidity, in vitro starch hydrolysis, and in vivo glucose response. Results: There was no significant difference in the total starch, cooking loss, and turbidity. The resistant starch of GN (1.70%) and CGN (1.84%) was significantly increased when compared with that in Naengmyeon with no additives (N) and CN. In terms of water absorption, CN (86.01%) was the lowest in samples, followed by GN (92.17%), N (94.20%), and CGN (99.16%). CGN with high resistant starch was the lowest in in vitro starch hydrolysis in samples. However, it had no effect on the in vivo glucose response. In vitro starch hydrolysis exhibited a significant positive correlation (r=0.533; p<0.01) with in vivo glucose response. Conclusion: Therefore, future studies are needed to establish the standard for resistant starch contents in processed carbohydrate foods for delaying the increase in blood glucose. If this standard is established, it might help to develop processed foods for diabetic patients.

• Journal of Applied Biological Chemistry
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• v.63 no.3
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• pp.181-188
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• 2020

In this study, Tongue fern (Pyrrosia lingua) plants that have been used traditionally as medicines. Their traditional medicinal uses, regions where indigenous people use the plants, parts of the plants used as medicines. This study was designed to assess the antioxidant and inhibition activities of extracts from P. lingua. In the P. lingua extracts was measured ethanol activity, 80.0% ethanol was high activity. The antioxidant activity was measured in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), assays. DPPH and ABTS radical in this experiment, solid and phenolic of extract were tested, but only an average concentration of 100 ㎍/mL was used. However, the phenolic extract is shown phenolic activity reached a peak. Also, phenolic extracts ware reached peak water and ethanol extracts. As a result, using the phenolic extracts did other antioxidant assays such as DPPH, ABTS, protection factor, and thiobarbituric acid reactive substances at 50-200 ㎍/mL concentrations. The activity of elastase and collagenase, inhibiting their activities may retard skin aging. α-Glucosidase and α-amylase, inhibitors need to be explored for the benefit of postprandial hyperglycemia in diabetic patients. Activities of tyrosinase, hyaluronidase and xanthine oxidase inhibitors of these enzymes are increasingly important ingredients in cosmetics and medications to protect the skin against hyperpigmentation and skin aging. Inhibition effects were investigated using the P. lingua extracts at 50-200 ㎍/mL concentrations. The expression levels of enzyme inhibitions activities were decrease in dependent-concentrations manner when P. lingua extracts were treated.