trans-Resveratrol (t-RVT), a naturally occurring polyphenol found in Polygonum cuspidatum, grape, and red wine, has been reported to have antiinflammatory, cardioprotective, and cancer chemopreventive properties. However antidiabetic effect of t-RVT has not yet been reported. In this study, we show that t-RVT increases glucose uptake in C2C12 myotubes by activating AMP-activated protein kinase (AMPK), uncovering an antidiabetic potential of t-RVT for the first time. AMPK plays a central role in the regulation of glucose and lipid metabolism, and hence it is considered a novel therapeutic target for metabolic syndrome such as type 2 diabetes. t-RVT significantly induced glucose uptake in C2C12 cells, via AMPK activation, but not a phosphatidylinositol-3 kinase (PI-3 kinase) signal pathway. The induced glucose uptake was attenuated by pretreatment with a pharmacological inhibitor for AMPK, indicating that the effect of t-RVT primarily depends on AMPK activation. However, in the presence of insulin, t-RVT also potentiated the effect of insulin on glucose uptake via AMPK activation, which led to further activation of PI-3 kinase/Akt signal pathway.

Epidemiological evidence suggests a lower incidence of prostate cancer in Asian countries, where soy products are more frequently consumed than in Western countries, indicating that isoflavones from soy have chemopreventive activities in prostate cells. Here, we tested the effects of the soy isoflavone genistein on antioxidant enzymes in DU145 prostate cancer cells. Genistein significantly decreased reactive oxygen species levels and induced the expression of the antioxidant enzymes manganese (Mn) superoxide dismutase (SOD) and catalase, which were associated with AMP-activated protein kinase (AMPK) and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathways. The induced expression of catalase, MnSOD, and PTEN were attenuated by pretreatment with a pharmacological inhibitor for AMPK, indicating the effects of genistein primarily depend on AMPK. Furthermore, PTEN is essential for genistein activity, as shown by PTEN transfection in PTEN-deficient PC3 cells. Thus, genistein induces antioxidant enzymes through AMPK activation and increased PTEN expression.

No abstract

To evaluate the role of heat shock 70 protein (HSP70) in free-living amoeba, a constitutive and inducible heat shock 70 gene of pathogenic Naegleria fowleri has previously been cloned, characterized, and named as NfcHSP70. The Nf-cHSP70 is localized in the cytoplasm, pseudopodia, and phagocytic food-cups. To investigate the role of Nf-cHSP70 in the pathogenicity of N. fowleri, the synthesis of N. fowleri HSP70 was first inhibited with benzylidene lactam compound (KNK437), and Nf-cHSP70 gene was knock-downed with antisense oligomers, which were designed with a start region-specific antisense oligonucleotides (24 oligomers) and modified with phosphorothioate. KNK437 inhibited the induction of N. fowleri HSP70 in a dose-dependent manner. In addition, 300 μM KNK437 reduced the proliferation of N. fowleri to 79.4% of untreated control (100%). Nf-cHSP70 knock-downed N. fowleri with antisense oligomers showed 68.5% reduction of proliferation in comparison with untreated control (100%). The cytotoxicity of N. fowleri against CHO target cells was reduced to 42.1% by KNK437 and 68.6% by antisense oligomers. These results suggest that the cloned Nf-cHSP70 plays an important role in the proliferation and cytotoxicity of pathogenic N. fowleri.

Women experience more stress in middle age than in other life stages, and health in middle age is vital, because it influences the quality of life in old age. In this study, the effects of a forest therapy program on physiological changes in 53 middle-aged women (divided into two groups) who lived in the city were examined. One group participated in a three-day program in the forest, followed by three days in the city; the other group participated in a three-day program in the city, followed by three days in the forest. Forest experiments were conducted in a “healing forest,” and urban experiments were conducted near a university campus. Blood tests were performed to evaluate the physiological effects of forest therapy. Differences in serotonin levels and vitamin D levels were verified before and after the forest (experimental group) and urban (control group) programs through paired t-tests. Statistically significant increases in serotonin levels were noted for participants in the forest program; vitamin D levels also increased, but not by statistically significant values. The findings of this study verify that forest therapy programs promote health among middle-aged women, and may prevent disease and improve quality of life.

Inulin, a naturally occurring, functional food ingredient found in various edible plants, has been reported to exert potential health benefits, including decreased risk of colonic diseases, non-insulin-dependent diabetes, obesity, osteoporosis, and cancer. However, the mechanism of the antidiabetic activity of inulin has not yet been elucidated. In this study, we showed that inulin increased the uptake of glucose in C2C12 myotubes, which was associated with both AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3-K) signaling pathways, but both of these pathways appeared to transmit their signals in an independent manner. Moreover, we found that inulin was able to increase the uptake of glucose in C2C12 myotubes in which insulin resistance was induced by exposing cells to high glucose concentrations. The identical effects of inulin were also observed in HepG2 hepatoma cells. Collectively, we report the antidiabetic activity of inulin and further demonstrate for the first time that such activity is associated with AMPK and PI3-K activation.

The purpose of this study is to look at these relationships in non-diabetic Korean adults. This study was based on data from the KNHANES V-1, which is representative of the population of Korea. A total of 5,492 participants (≥20 years in age) without type 1 or type 2 diabetes, assessed for serum 25-hydroxyvitamin D [25(OH)D], fasting blood glucose and insulin, as well as anthropometric variables, were included in the analyses. The key study results were as follows: First, vitamin D status [vitamin D deficient, 25(OH)D <25 nM; vitamin D insufficient, 25(OH)D ≥25, <50 nM; vitamin D sufficient, 25(OH)D ≥50 nM] was inversely associated with homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in model 2 (adjusted for age and gender) and 3 (further adjusted for smoking, alcohol drinking, regular exercise, systolic and diastolic blood pressure, waist circumference, and body mass index). Second, in model 4, when further adjusted for total cholesterol, triglycerides, and HDL-C, vitamin D status was inversely associated with HOMA-B. However, association of vitamin D status and HOMA-IR was no longer significant. In conclusion, vitamin D was inversely associated with beta cell function in non-diabetic Korean adults but was not associated with insulin resistance.

Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A 51Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-α, IL-6, and IL-1β, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.