Sun Yoon

Inhibition of IGF-1 Signaling by Genistein: Modulation of E-Cadherin Expression and Downregulation of β-Catenin Signaling in Hormone Refractory PC-3 Prostate Cancer Cells

Elevated levels of insulin-like growth factor-1 (IGF-1) are associated with an increased risk of several different cancers, including prostate cancer. Inhibition of IGF-1 and the downstream signaling pathways mediated by the activation of the IGF-1 receptor (IGF-1R) may be involved in inhibiting prostate carcinogenesis. We investigated whether genistein downregulated the IGF-1/IGF-1R signaling pathway and inhibited cell growth in hormone refractory PC-3 prostate cancer cells. Genistein treatment caused a significant inhibition of IGF-1-stimulated cell growth. Flow cytometry analysis revealed that genistein significantly decreased the number of IGF-1-stimulated cells in the G0/G1 phase of the cell cycle. In IGF-1-treated cells, genistein effectively inhibited the phosphorylation of IGF-1R and the phosphorylation of its downstream targets, such as Src, Akt, and glycogen synthase kinase-3β (GSk-3β). IGF-1 treatment decreased the levels of E-cadherin but increased the levels of β-catenin and cyclin D1. However, genistein treatment greatly attenuated IGF-1-induced β-catenin signaling that correlated with increasing the levels of E-cadherin and decreasing cyclin D1 levels in PC-3 cells. In addition, genistein inhibited T-cell factor/lymphoid enhancer factor (TCF/LEF)-dependent transcriptional activity. These results showed that genistein effectively inhibited cell growth in IGF-1-stimulated PC-3 cells, possibly by inhibiting downstream of IGF-1R activation.

Lipid raft cholesterol and genistein inhibit the cell viability of prostate cancer cells via the partial contribution of EGFR-Akt/p70S6k pathway and down-regulation of androgen receptor

Soy isoflavones and cholesterol have been reported as dietary factors related to the incidence of prostate cancer. In this study, we investigated whether cell survival could be suppressed by a combination of the dispersion of lipid raft microdomains and treatment with genistein, a well-known potential isoflavone, in LNCaP prostate cancer cells. Cell viability was assayed by the property of reagent change upon reduction of resazurin to resorufin and apoptosis was evaluated by ethidium bromide/acridine orange (EB/AO) staining and PARP and caspase-3 expression. Signal transduction was investigated by immunoblot analysis. Cell viability decreased significantly more following successive double treatment with genistein and the cholesterol-lowering agent 2-hydroxypropyl-beta-cyclodextrin (HPCD) than in response to either agent alone. Apoptotic cell staining and cleavage of PARP and caspase-3 appeared more clearly in double-treated cells than in those treated with genistein alone. In cell signaling, both HPCD and genistein decreased the protein expressions of pAkt as well as the androgen receptors stimulated by EGF and DHT, respectively, in concentration-dependent manners. This pattern was also present in protein levels of pAkt and the androgen receptor located in the lipid raft fraction. Furthermore, the phosphorylation cascade of Akt, GSK-3beta and p70S6k was markedly inhibited by the combination treatment. These data suggest that prostate cancer cells could be effectively inhibited by combination treatment of cholesterol-lowering strategies and genistein. The mechanism is likely to be partially via both the EGFR-mediated Akt or p70S6k pathways and a down-regulation of androgen receptor in the lipid raft microdomain.

The effects of A. senticosus supplementation on serum lipid profiles, biomarkers of oxidative stress, and lymphocyte DNA damage in postmenopausal women

This study examined the effects of Acanthopanax senticosus supplementation on serum lipid profiles, biomarkers of oxidative stress, and lymphocyte DNA damage in postmenopausal women. Forty postmenopausal women, ages 40-65, were randomly divided into two groups: (1) control group (calcium) and (2) treatment group (calcium plus A. senticosus). Both groups were treated for 6 months. Blood samples were obtained before and after supplementation at 6 months. The following blood parameters were measured: serum total cholesterol, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), serum malondialdehyde (MDA), ccdd protein-carbonyl (PC) levels, the degree of lymphocyte DNA damage by comet assay, total ferric reducing antioxidant power (FRAP), uric acid, and total bilirubin in serum. The treatment group had significant decreases (p<0.001) in serum LDL (127.54+/-29.79mg/dL vs 110.33+/-22.26mg/dL) and the LDL/HDL ratio (2.40+/-0.65 vs 2.11+/-0.58) after A. senticosus supplementation. Serum MDA concentrations decreased by 2.2% in the control group and by 12.61% in the treatment group after 6 months of intervention; however, the reductions were not significant in either group. Protein-carbonyl levels and lymphocyte DNA damage decreased significantly (p<0.001 and p<0.05, respectively) after 6 months of A. senticosus supplementation. These results suggest that A. senticosus supplementation may have beneficial effects against oxidative stress and improve serum lipid profiles without subsequent side effects.

Fermentation of Soy Milk via Lactobacillus plantarum Improves Dysregulated Lipid Metabolism in Rats on a High Cholesterol Diet

We aimed to investigate whether in vitro fermentation of soy with L. plantarum could promote its beneficial effects on lipids at the molecular and physiological levels. Rats were fed an AIN76A diet containing 50% sucrose (w/w) (CTRL), a modified AIN76A diet supplemented with 1% (w/w) cholesterol (CHOL), or a CHOL diet where 20% casein was replaced with soy milk (SOY) or fermented soy milk (FSOY). Dietary isoflavone profiles, serum lipids, hepatic and fecal cholesterol, and tissue gene expression were examined. The FSOY diet had more aglycones than did the SOY diet. Both the SOY and FSOY groups had lower hepatic cholesterol and serum triglyceride (TG) than did the CHOL group. Only FSOY reduced hepatic TG and serum free fatty acids and increased serum HDL-CHOL and fecal cholesterol. Compared to CHOL, FSOY lowered levels of the nuclear forms of SREBP-1c and SREBP-2 and expression of their target genes, including FAS, SCD1, LDLR, and HMGCR. On the other hand, FSOY elevated adipose expression levels of genes involved in TG-rich lipoprotein uptake (ApoE, VLDLR, and Lrp1), fatty acid oxidation (PPARα, CPT1α, LCAD, CYP4A1, UCP2, and UCP3), HDL-biogenesis (ABCA1, ApoA1, and LXRα), and adiponectin signaling (AdipoQ, AdipoR1, and AdipoR2), as well as levels of phosphorylated AMPK and ACC. SOY conferred a similar expression profile in both liver and adipose tissues but failed to reach statistical significance in many of the genes tested, unlike FSOY. Our data indicate that fermentation may be a way to enhance the beneficial effects of soy on lipid metabolism, in part via promoting a reduction of SREBP-dependent cholesterol and TG synthesis in the liver, and enhancing adiponectin signaling and PPARα-induced expression of genes involved in TG-rich lipoprotein clearance, fatty acid oxidation, and reverse cholesterol transport in adipose tissues.

Elevated-CPW for high-speed digital interconnects

An elevated coplanar waveguide is one in which the signal line is elevated. An elevated-CPW (ECPW) with low loss and low dispersion characteristics is proposed for high-speed digital circuits and its performance is predicted by theoretical analysis. The ECPW is simulated with FDTD and is fabricated as a 10 /spl mu/m elevated CPW using thick film micromachining technology and a polymide buffer layer. An ECPW has 10 dB lower insertion loss than the conventional CPW, and the effective permittivity is in the range of 1 to 3. Characteristic impedances and effective permittivity are given for various geometrical parameters.

Combined treatment of isoflavone supplementation and exercise restores the changes in hepatic protein expression in ovariectomized rats - a proteomics approach.

BackgroundPostmenopausal women experience adverse physiological changes caused by estrogen deprivation. Here, we hypothesized that the administration of isoflavone, a phytoestrogn, and/or physical exercise could reverse changes in the levels of hepatic enzymes disturbed by loss of estrogen to ameliorate postmenopause-related health problems.MethodsThirty-week-old female Sprague–Dawley rats were divided into five groups: a sham-operated (SHAM) group, ovariectomized groups on a regular diet with exercise (EXE) and without exercise (OVX), and ovariectomized groups on an isoflavone supplemented diet with (ISO + EXE) and without exercise (ISO). Proteomic tools were employed to identify candidate hepatic proteins that were differentially expressed among the five animal groups.ResultsINMT was detected in the SHAM but not in all of the ovariectomized rats. Seven proteins (PPIA, AKR1C3, ALDH2, PSME2, BUCS1, OTC, and GAMT) were identified to have differential expression among the groups. When compared to the SHAM group, the ovariectomy elevated the levels of PPIA, BUCS1, PSME2, AKR1C3, and GAMT while decreasing ALDH2 and OTC. Among these OVX-induced changes, OVX-increased BUCS1 and GAMT levels were noticeably decreased by ISO or EXE and further greatly down-regulated by ISO + EXE. In the case of PSME2, ISO and EXE further increased OVX-upregulated expression levels but ISO + EXE greatly reduced OVX-increased levels. On the other hand OVX-lowered OTC levels were elevated by ISO, EXE, or ISO + EXE. The protein levels of ALDH2, PPIA, and AKR1C3 were not significantly reverted by ISO, EXE or ISO + EXE.ConclusionThe combination of an isoflavone diet and exercise partly reversed ovariectomy-induced changes in hepatic protein expression levels. Our data suggest that the combinatory regimen of isoflavone supplementation and exercise may be beneficial to menopausal women through modulating hepatic protein expression profiles.

Fermentation of broken rice using kimchi-derived Weissella koreensis HO20 and its use in Jeungpyeon

Broken rice was fermented by Weissella koreensis HO20 isolated from kimchi, and its fermentation characteristics and application in the making of jeungpyeon were studied. Broken rice flour had higher amounts of crude protein, crude fat, crude ash, reducing sugars, and damaged starch, but a significantly lower content of amylose than head rice flour. Acidification by W. koreensis was much faster in broken rice dough (14 h) than in head rice dough (30 h) to reach the terminal pH 4.5 at 25°C. Fermentation significantly reduced peak, setback, and breakdown viscosities of rice flours. Consumer preference of jeungpyeon was not significantly different whether it is made of broken rice or head rice. However, jeungpyeon made of fermented rice dough was preferred to that of unfermented rice dough. The results of this study strongly suggest that broken rice can be successfully fermented by W. koreensis and can be used to make jeungpyeon with good organoleptic properties.

Soy milk suppresses cholesterol-induced inflammatory gene expression and improves the fatty acid profile in the skin of SD rats

Recently, an elevation in skin cholesterol level has been implicated in skin inflammation. Given the potential therapeutic effects of soy on low grade inflammatory diseases, we hypothesized that a CHOL diet could promote an inflammatory response in skin and that soy milk (SM) or fermented soy milk (F.SM) could prevent this cholesterol-induced skin inflammation. To test this hypothesis, freeze-dried SM or F.SM was provided as a protein replacement for 20% of the casein in the diets of Sprague-Dawley (SD) rats. The animals were divided into the following groups: (1) control group (CTRL), AIN76A diet without cholesterol, (2) high cholesterol (CHOL) group, AIN76A with 1% (w/w) cholesterol, (3) SM group, CHOL diet with freeze-dried SM, and (4) F.SM group, CHOL diet with F.SM. In the CHOL group, the expression levels of pro-inflammatory genes, including IL-1β, IL-1α, iNOS, and COX-2, were elevated. In comparison, the SM and F.SM groups displayed the lowered expression of IL-1β, COX-2, F4/80, and Cd68, an increase of a n-3/n-6 ratio, and a reduction in the estimated desaturase activities of delta 5 desaturase (D5D) and steaoryl CoA desaturase (SCD-1). In particular, F.SM significantly increased the proportion of dihomo-γ-linolenic acid (DGLA) in skin fatty acid (FA) composition compared with the CHOL group. Here we present evidence that SM or F.SM could alleviate the inflammatory response in the skin that is triggered by excess dietary cholesterol by reducing the expression of pro-inflammatory genes. This response could be partly associated with a decreased in macrophages in skin and/or by modulation of the skins FA composition.

Hydrocolloids Decrease the Digestibility of Corn Starch, Soy Protein, and Skim Milk and the Antioxidant Capacity of Grape Juice

Hydrocolloids have many applications in foods including their use in dysphagia diets. We aimed to evaluate whether hydrocolloids in foods affect the digestibility of starch and protein, and their effects on antioxidant capacity. The thickening hydrocolloids: locust bean gum and carboxymethyl cellulose, and the gel-forming agents: agar agar, konjac-glucomannan, and Hot & Soft Plus were blended with corn starch and soy protein, skim milk, or grape juice and were examined for their in vitro-digestability by comparing the reducing sugar and trichloroacetic acid (TCA)-soluble peptide, for antioxidant capacity by total polyphenol contents and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. The hydrocolloids resulted in a decrease in starch digestibility with the gel-forming agents. Hydrocolloids diminished TCA-soluble peptides in skim milk compared to soy protein with the exception of locust bean gum and decreased free radical scavenging capacities and total phenolic contents in grape juice. Our findings may provide evidence for the use of hydro-colloids for people at risk of nutritional deficiencies such as dysphagia patients.

Development and application of a web-based nutritional management program to improve dietary behaviors for the prevention of metabolic syndrome.

The purpose of this study was to develop a Web-based nutritional management program for the prevention of metabolic syndrome and to evaluate how the program affects health-related behaviors and the health status of office workers with metabolic syndrome risk factors. For the pilot test of the Web-based nutritional management program, 29 employees (19 males, 10 females) with more than one metabolic syndrome risk factor participated in the Web-based nutritional management program for 16 weeks. Participants visited the Web site more than two times per week and completed customized assessments of health status, smoking habits, alcohol consumption, dietary habits, food intake, ideal body weight, energy requirements, and exercise. Subjects had a significant decrease in body weight, waist circumference, body mass index (P < .01 in males, P < .05 in females), and body fat (P < .01 in males). The frequency of dietary habits such as eating snacks, eating out, and dining with others decreased, whereas the frequency of intake of foods such as whole grains, seaweed, fruit, and low-fat milk increased after intervention. After 16 weeks, program satisfaction was evaluated using a Web evaluation questionnaire, and most of the participants were highly satisfied with Web site components such as the loading speed, configuration, privacy, design, functionality, and contents.