PurposeαB-crystallin, a small heat shock protein, is an anti-apoptotic protein associated with aggressive tumor behavior. A recent study revealed that αB-crystallin is overexpressed in a metastatic variant of the GI101A human breast carcinoma cell line. The purpose of this study was to investigate whether αB-crystallin is related to other breast tumor markers and can predict a breast cancer prognosis.MethodsEighty-two patients who underwent breast cancer surgery at Hallym Sacred Heart Hospital were enrolled. αB-crystallin expression was determined by immunohistochemical staining. Estrogen receptor, progesterone receptor (PR), human epidermal growth factor receptor, lymphovascular invasion, histological grade, other tumor markers and time to recurrence were compared with αB-crystallin expression.ResultsαB-crystallin expression in breast cancer tissues was associated with PR (p=0.030), the number of metastatic lymph nodes (pN) (p=0.020), lymphovascular invasion (p=0.022), histological grade (p=0.004) and triple negative breast cancer (TNBC) (p=0.004). αB-crystallin expression significantly decreased time to recurrence (p=0.039).ConclusionThe results revealed a strong relationship between αB-crystallin and poor prognostic factors such as the number of metastatic lymph nodes (especially pN2), TNBC, and rapid time to recurrence. We believe that αB-crystallin could be a novel oncoprotein biomarker of a poor prognosis in breast cancer.

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)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(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 ϭ 0.024), higher fasting glucose concentration (P ϭ 0.007) 2 months postpartum, and lower 1-h insulin concentration (P ϭ 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.

L. platyphylla is a perennial herb plant that is widely-distributed in temperate climate regions of the northern hemisphere. In Korea, these plants mainly grow mountainous regions at low altitude (i.e., <500 m sea level) and their leaves remain green year-round (Huh et al., 2007). L. platyphylla has been the basis of a traditional oriental herbal medicine that has been long-used for the treatment of asthma and bronchial and lung infl ammation (Lee et al., 2005). Data from several sciencebased studies has demonstrated the therapeutic effectiveness of the extract of the roots of L. platyphylla in the treatment of obesity, diabetes and neurodegenerative disease (Choi et al., Liriope platyphylla is a medical herb that has long been used in Korea and China to treat cough, sputum, neurodigenerative disorders, obesity and diabetes. The aims of this study were to study the antidiabetic effects of the aqueous extract of L. platyphylla (AEtLP) through pancreatic and extrapancreatic actions. AEtLP were orally administrated to ICR mice once a day for 7 days. Of three different concentrations of AEtLP, only 10% AEtLP were low toxic to liver, based on body weight and serum biochemical analyses. However, 10% AEtLP-treated mice displayed signifi cant reduction of the glucose concentration and increased insulin concentration; no changes were noted using 5% and 15% AEtLP. Also, the increase of glucose transporter (Glut)-1 expression in liver was dependent on the concentration of AEtLP, and was regulated by the phosphorylation of Akt. The lowest expression of Glut-3 was observed in 15% AEtLP treated mice, followed by 10% AEtLP-and 5% AEtLP-treated mice. This pattern of Glut-3 expression was roughly in accord with the phosphorylation of c-Jun N-teminal kinase (JNK) in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, a signifi cant rise of the superoxide dismutase activity (SOD) was detected in AEtLP-treated mice. The fi ndings suggest that AEtLP should be considered as a diabetes therapeutic candidate to induce insulin secretion from pancreatic β-cells and glucose uptake in liver cells. Department of Experimental Animal Research, Clinical Research Institute, Seoul National University Hospital, 6 College of Pharmacy, Chungbuk National University, Chungju 361-763, Republic of Korea Abstract 2004;Hur et al., 2004;Jeong et al., 2008;Hur et al., 2009). Anti-infl amation and anti-microbial effects have been studied for a very long time. Kim et al. (2002) screened the extracts of many plants for anti-bacterial effects drugs via the detection of the inhibition of sortase (an enzyme found in most Gram-positive bacteria that is important in bacterial adhesion). Among 80 medical plants tested, L. platyphylla, Cocculus trilobus, Fritillaria verticillata, and Rhus vernicifl ua had strong anti-bacterial activity. Also, L. platyphylla potently inhibits airway infl ammation and hyperresponsiveness in a murine model of asthma by modulating the relationship between Th1/Th2 cytokine imbalance (Lee et al., 2005) as well as a...

The serine/threonine kinase Akt has been shown to play a role of multiple cellular signaling pathways and act as a transducer of many functions initiated by growth factor receptors that activate phosphatidylinositol 3-kinase (PI3K). It has been reported that phosphorylated Akt activates eNOS resulting in the production of NO and that NO stimulates soluble guanylate cyclase (sGC), which results in accumulation of cGMP and subsequent activation of the protein kinase G (PKG). It has been also reported that PKG activates PI3K/Akt signaling. Therefore, it is possible that PI3K, Akt, eNOS, sGC, and PKG form a loop to exert enhanced and sustained activation of Akt. However, the existence of this loop in eNOS-expressing cells, such as endothelial cells or astrocytes, has not been reported. Thus, we examined a possibility that Akt phosphorylation might be enhanced via eNOS/ sGC/PKG/PI3K pathway in astrocytes in vivo and in vitro. Phosphorylation of Akt was detected in astrocytes after KA treatment and was maintained up to 72 h in mouse hippocampus. 2 weeks after KA treatment, astrocytic Akt phosphorylation was normalized to control. The inhibition of eNOS, sGC, and PKG significantly decreased Akt and eNOS phosphorylation induced by KA in astrocytes. In contrast, the decreased phosphorylation of Akt and eNOS by eNOS inhibition was significantly reversed with PKG activation. The above findings in mouse hippocampus were also observed in primary astrocytes. These data suggest that Akt/eNOS/sGC/PKG/PI3K pathway may constitute a loop, resulting in enhanced and sustained Akt activation in astrocytes.

Background. Nobiletin is a natural compound with anticancer activity; however, the mechanism is not clear. Methods. The inhibitory effect of nobiletin on non-small-cell lung cancer (NSCLC) cells was examined using soft agar, Transwell, and apoptosis analyses. Cancer stemness was measured by sphere assay. Genes and miRNAs regulated by nobiletin were identified by whole-genome sequencing. Protein levels were detected by western blot and immunofluorescence assays. Results. Nobiletin significantly inhibited NSCLC cell colony formation and sphere formation and induced apoptosis. Nobiletin upregulated negative regulators of WNT/β-catenin signaling, including NKD1, AXIN2, and WIF1, while it inhibited the expression of β-catenin and its downstream genes, including c-Myc, c-Jun, and cyclin D1. Furthermore, we identified that GN inhibits miR-15-5p expression in NSCLC cells and that NKD1, AXIN2, and WIF1 are the target genes of miR-15-5p. Conclusions. Nobiletin has a strong inhibitory effect on NSCLC, and nobiletin plays an anticancer role by inhibiting miR-15-5p/β-catenin signaling in NSCLC.