The involvement of AMPK/GSK3-beta signals in the control of metastasis and proliferation in hepato-carcinoma cells treated with anthocyanins extracted from Korea wild berry Meoru

BACKGROUND: Activation of the Wnt pathway is known to promote tumorigenesis and tumor metastasis, and targeting Wnt pathway inhibition has emerged as an attractive approach for controlling tumor invasion and metastasis. The major pathway for inhibiting Wnt is through the degradation of β-catenin by the GSK3-beta/CK1/Axin/APC complex. It was found that Hep3B hepato-carcinoma cells respond to anthocyanins through GSK3-beta-induced suppression of beta-catenin; however, they cannot dephosphorylate GSK3-beta without AMPK activation. METHODS: We tested the effects of anthocyanins on proliferation and apoptosis by MTT and Annexin V-PI staining in vitro. Mouse xenograft models of hepato-carcinomas were established by inoculation with Hep3B cells, and mice were injected with 50 mg/kg/ml of anthocyanins. In addition, protein levels of p-GSK3-beta, beta-catenin, p-AMPK, MMP-9, VEGF, and Ang-1 were also analyzed using western blot. RESULTS: Anthocyanins decrease phospho-GSK3-beta and beta-catenin expression in an in vivo tumor xenograft model, increase AMPK activity in this model, and inhibit cell migration and invasion, possibly by inhibiting MMP-2 (in vitro) and the panendothelial marker, CD31 (in vivo). To elucidate the role of the GSK3-beta/beta-catenin pathway in cancer control, we conditionally inactivated this pathway, using activated AMPK for inhibition. Further, we showed that AMPK siRNA treatment abrogated the ability of anthocyanins to control cell proliferation and metastatic potential, and Compound C, an AMPK inhibitor, could not restore GSK3-beta regulation, as exhibited by anthocyanins in Hep3B cells. CONCLUSION: These observations imply that the AMPK-mediated GSK3-beta/beta-catenin circuit plays crucial roles in inhibiting cancer cell proliferation and metastasis in anthocyanin-treated hepato-carcinoma cells of Meoru origin

Regulation of Proinflammatory Mediators via NF-κB and p38 MAPK-Dependent Mechanisms in RAW 264.7 Macrophages by Polyphenol Components Isolated from Korea Lonicera japonica THUNB

Lonicera japonica THUNB., which abundantly contains polyphenols, has been used as a traditional medicine for thousands of years in East Asian countries because of the anti-inflammation properties. This study aimed to investigate the anti-inflammatory mechanism of polyphenol components isolated from Korea L. japonica T. by nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathway. Polyphenols significantly decreased lipopolysaccharide- (LPS-) induced mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as mRNA expression of tumor necrosis factor-alpha, interleukin- (IL-) 1β, and IL-6. Moreover, polyphenols inhibited nuclear translocation of NF-κB p65, phosphorylation/degradation of the inhibitor of κB, and phosphorylation of p38 MAPK, whereas the extracellular signal-regulated kinase and Janus N-terminal kinase were not affected. These results indicate that polyphenol components isolated from Korea L. japonica T. should have anti-inflammatory effect on LPS-stimulated RAW 264.7 cells through the decrease of proinflammatory mediators expression by suppressing NF-κB and p38 MAPK activity

Flavonoids Isolated from Korea Citrus aurantium L. Induce G2/M Phase Arrest and Apoptosis in Human Gastric Cancer AGS Cells

Aim of the Study. Citrus species is used in traditional medicine as medicinal herb in several Asian countries including Korea. Flavonioids became known as various properties, such as anti-oxidants, anti-inflammation and anti-cancer, and so forth. The present study, the anti-cancer effect of flavonioids isolated from Citrus aurantium L. in human gastric cancer AGS cells has been investigated. Materials and Methods. The anti-proliferative activity was assayed using MTT assay. Cell cycle analysis was done using flow cytometry and apoptosis detection was done using by hoechst fluorescent staining and Annexin V-propidium iodide double staining. Western blot was used to detect the expression of protein related with cell cycle and apoptosis. Results. Flavonoids isolated from Citrus aurantium L. have the effect of anti proliferation on AGS cells with IC50 value of 99 μg/mL. Flavonoids inhibited cell cycle progression in the G2/M phase and decrease expression level of cyclin B1, cdc 2, cdc 25c. Flavonoids induced apoptosis through activate caspase and inactivate PARP. Conclusions. Flavonoids isolated from Citrus aurantium L. induced G2/M phase arrest through the modulation of cell cycle related proteins and apoptosis through activation caspase. These finding suggest flavonoids isolated from Citrus aurantium L. were useful agent for the chemoprevention of gastric cancer

Expression of Heterologous OsDHAR Gene Improves Glutathione (GSH)-Dependent Antioxidant System and Maintenance of Cellular Redox Status in Synechococcus elongatus PCC 7942.

An excess of reactive oxygen species (ROS) can cause severe oxidative damage to cellular components in photosynthetic cells. Antioxidant systems, such as the glutathione (GSH) pools, regulate redox status in cells to guard against such damage. Dehydroascorbate reductase (DHAR, EC 1.8.5.1) catalyzes the glutathione-dependent reduction of oxidized ascorbate (dehydroascorbate) and contains a redox active site and glutathione binding-site. The DHAR gene is important in biological and abiotic stress responses involving reduction of the oxidative damage caused by ROS. In this study, transgenic Synechococcus elongatus PCC 7942 (TA) was constructed by cloning the Oryza sativa L. japonica DHAR (OsDHAR) gene controlled by an isopropyl β-D-1-thiogalactopyranoside (IPTG)-inducible promoter (Ptrc) into the cyanobacterium to study the functional activities of OsDHAR under oxidative stress caused by hydrogen peroxide exposure. OsDHAR expression increased the growth of S. elongatus PCC 7942 under oxidative stress by reducing the levels of hydroperoxides and malondialdehyde (MDA) and mitigating the loss of chlorophyll. DHAR and glutathione S-transferase activity were higher than in the wild-type S. elongatus PCC 7942 (WT). Additionally, overexpression of OsDHAR in S. elongatus PCC 7942 greatly increased the glutathione (GSH)/glutathione disulfide (GSSG) ratio in the presence or absence of hydrogen peroxide. These results strongly suggest that DHAR attenuates deleterious oxidative effects via the glutathione (GSH)-dependent antioxidant system in cyanobacterial cells. The expression of heterologous OsDHAR in S. elongatus PCC 7942 protected cells from oxidative damage through a GSH-dependent antioxidant system via GSH-dependent reactions at the redox active site and GSH binding site residues during oxidative stress

Associations between maternal stress during pregnancy and offspring internalizing and externalizing problems in childhood

BACKGROUND: Maternal psychological health during pregnancy has been associated with offspring psychopathology. However, it is uncertain whether these associations are mediated by the postpartum depression and related child-rearing factors. Therefore, we examined the associations between prenatal and postnatal factors and internalizing and externalizing behavioral problems in childhood, focusing on maternal psychological health in school-aged children in Korea. FINDINGS: The current study included 1,003 children (580 boys, 423 girls, mean age 9.05 ± 0.70 years, age range 8–11 years) recruited from schools in five Korean cities. Children’s internalizing and externalizing problems were assessed by the Child Behavior Checklist (CBCL). The parents of the children completed structured questionnaires on perinatal factors. Among 1,003 children, 44 had internalizing problems (IP) and 30 had externalizing problems (EP). When comparing children with IP (n = 44) and without IP (n = 959), severe maternal stress during pregnancy (OR3.36, 95% CI 1.80-6.25) and postpartum depression (OR3.19, 95% CI 1.36-7.53) showed a significant association with the IP. When comparing children with EP (n = 30) and without EP (n = 973), low family income (OR2.19, 95% CI 1.05-4.56), unwanted pregnancy (OR2.76, 95% CI 1.28-5.95) and severe maternal stress during pregnancy (OR2.69, 95% CI 1.29-5.61) with the EP. Only maternal stress during pregnancy was significantly associated with the IP after controlling for postpartum depression and with the EP after controlling for family income and unwanted pregnancy. CONCLUSION: This study suggests the importance of maternal psychological health during perinatal period on children’s mental health. Further prospective studies in a larger sample are required to confirm our findings

Irreversible extinction of ferroelectric polarization in P(VDF-TrFE) thin films upon melting and recrystallization

We observed the irreversible extinction of ferroelectric polarization in spun coated poly(vinylidene fluoride-co-trifluoroethylene) thin films upon melting and recrystallization. We investigate the alteration of the ferroelectric properties correlated with the preferred polymer crystal orientation with respect to the electrodes using grazing incident scattering, spectroscopy, and electron microscopes. Heat treatment above melting point gave rise to the significant reduction of the ferroelectric performance mainly caused by the modification of molecular orientation of polymer crystals whose c and b axes are perpendicular and parallel to the electrode surface, respectively, leading to almost zero effective electric field. (c) 2006 American Institute of Physicsopen464

Suppressive Effect on Lipopolysaccharide-Induced Proinflammatory Mediators by Citrus aurantium L. in Macrophage RAW 264.7 Cells via NF-κB Signal Pathway

Citrus fruits have been used as an edible fruit and a traditional medicine since ancient times. In particular, the peels of immature citrus fruits are used widely in traditional herbal medicine in Korea, as they are believed to contain bioactive components exerting anti-inflammatory activity. This study examined whether the crude methanol extract of Citrus aurantium L. (CME) has a suppressive effect on inducible enzymes and proinflammatory cytokines by inhibiting the NF-κB pathway in LPS-stimulated macrophage RAW 264.7 cells. The cells were pretreated with the indicated concentrations of CME (5, 10, 20, and 50 μg/mL) and then treated with LPS (1 μg/mL). The results showed that CME (10, 20, and 50 μg/mL) inhibited the LPS- (1 μg/mL) induced mRNA and protein expression of iNOS in macrophage Raw 264.7 cells. In addition, the expression of COX-2 was inhibited at the mRNA and protein levels by CME in a dose-dependent manner. The mRNA expression of proinflammatory cytokines, such as TNF-α and IL-6, were markedly reduced by CME (10, 20, and 50 μg/mL). Moreover, CME clearly suppressed the nuclear translocation of the NF-κB p65 subunits, which was correlated with its inhibitory effect on I-κB phosphorylation. These results suggest that CME has anti-inflammatory properties by modulating the expression of COX-2, iNOS, and proinflammatory cytokines, such as TNF-α and IL-6, in macrophage RAW 264.7 cells via the NF-κB pathway

Leisure sedentary time is differentially associated with hypertension, diabetes mellitus, and hyperlipidemia depending on occupation

Abstract Background Sedentary behavior is considered an independent cause of cardio-metabolic diseases, regardless of physical activity level and obesity. Few studies have reported the association between leisure sedentary time and cardio-vascular diseases in terms of occupation. Methods We performed a cross-sectional study using data from the Korean Community Health Survey (KCHS) for 240,086 participants assessed in 2011 and 2013. Occupation was categorized into four groups: farmer or fisherman, laborer, and soldier (Group I); service worker, salesperson, technician, mechanic, production worker, and engineer (Group II); manager, expert, specialist, and clerk (Group III); and unemployed (Group IV). Leisure sedentary time was divided into five groups: 0 h, 1 h, 2 h, 3 h, and 4+ h. The association between leisure sedentary time on weekdays and hypertension/diabetes mellitus/hyperlipidemia for different occupations was analyzed using simple and multiple logistic regression analyses with complex sampling. Results In Groups I, II and III, no length of sedentary time was associated with hypertension, and only 3 h or 4+ h of sedentary time was associated with diabetes mellitus and hyperlipidemia. Group IV showed a significant association with hypertension and diabetes mellitus for the 2 h, 3 h, and 4+ h sedentary times. Conclusions The unemployed are more susceptible than other occupation groups to cardio-metabolic diseases when leisure time is sedentary