Anti-diabetic effects of Ganoderma lucidum.

Ganoderma lucidum is a white rot fungus widely used as a tonic for the promotion of longevity and health. Extracts of G. lucidum have been recognized as an alternative adjuvant treatment for diabetes. Among the many biologically active constituents of G. lucidum, polysaccharides, proteoglycans, proteins and triterpenoids have been shown to have hypoglycemic effects. G. lucidum polysaccharides have been reported to have hypoglycemic activity by increasing plasma insulin levels and decreasing plasma sugar levels in mice. Protein tyrosine phosphatase 1B is a promising therapeutic target in diabetes, and G. lucidum proteoglycan can inhibit this enzyme in vitro. Moreover, G. lucidum triterpenoids were shown to have inhibitory activity on aldose reductase and α-glucosidase that can suppress postprandial hyperglycemia. In addition, a protein Ling Zhi-8 extracted from G. lucidum significantly decreased lymphocyte infiltration and increased the antibody detection of insulin in diabetic mice. This review summarizes most of the research about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins and tritrerpenoids from G. lucidum as a guide for future research.

GM2-activator protein: a new biomarker for lung cancer.

INTRODUCTION: Effective biomarkers for early diagnosis of lung cancer are needed. A recent study demonstrated that urinary GM2-activator protein (GM2AP) level was increased in lung cancer patients. This study aims to validate the potential application of GM2AP as a biomarker for diagnosis of lung cancer. METHODS: Serum and urine samples were obtained from 189 participants (133 patients for treatment naive lung cancer, 26 healthy volunteers for urine, and 30 healthy volunteers for serum). GM2AP level was detected by Western blotting and quantified using enzyme-linked immunosorbent assay (ELISA). The GM2AP expression in tumors and nontumor parts of lung tissues from 143 nonsmall cell lung cancers was detected by immunohistochemical stains. RESULTS: There was an 8.11 ± 1.36 folds increase in urine and a 5.41 ± 0.73 folds increase in serum level of GM2AP in lung cancer patients compared with healthy volunteers (p < 0.0001), achieving a 0.89 AUC value in urine and 0.90 AUC value in serum for the receiver-operating characteristic curves. Both serum and urine levels of GM2AP correlated significantly with pathology stages (urine, p = 0.009; serum, p < 0.0001). Using immunohistochemical, positive expression of GM2AP was found at 83.9% of nonsmall cell lung cancers patients and none in normal tissue. The GM2AP expression was significantly correlated with pathology stage (p = 0.0001). Patients with higher GM2AP expression had shorter overall survival (p = 0.045) and disease-free survival (p = 0.049) than lower GM2AP expression. Moreover, the multivariate analysis suggested GM2AP as an independent predictors of disease-free survival and overall survival. CONCLUSIONS: Our study demonstrates that GM2AP might serve as potential diagnostic and prognostic biomarkers in patients with lung cancer.

Nuclear ErbB2 enhances translation and cell growth by activating transcription of ribosomal RNA genes.

Aberrant regulation of rRNA synthesis and translation control can facilitate tumorigenesis. The ErbB2 growth factor receptor is overexpressed in many human tumors and has been detected in the nucleus, but the role of nuclear ErbB2 is obscure. In this study, we defined a novel function of nuclear ErbB2 in enhancing rRNA gene transcription by RNA polymerase-I (RNA Pol I). Nuclear ErbB2 physically associates with ß-actin and RNA Pol I, coinciding with active RNA Pol I transcription sites in nucleoli. RNA interference-mediated knockdown of ErbB2 reduced pre-rRNA and protein synthesis. In contrast, wild-type ErbB2 augmented pre-rRNA level, protein production, and cell size/cell growth, but not by an ErbB2 mutant that is defective in nuclear translocation. Chromatin immunoprecipitation assays revealed that ErbB2 enhances binding of RNA Pol I to rDNA. In addition, ErbB2 associated with rDNA, RNA Pol I, and ß-actin, suggesting how it could stimulate rRNA production, protein synthesis, and increased cell size and cell growth. Finally, ErbB2-potentiated RNA Pol I transcription could be stimulated by ligand and was not substantially repressed by inhibition of PI3-K and MEK/ERK (extracellular signal regulated kinase), the main ErbB2 effector signaling pathways. Together, our findings indicate that nuclear ErbB2 functions as a regulator of rRNA synthesis and cellular translation, which may contribute to tumor development and progression.

Myocyte enhancer factor-2 interacting transcriptional repressor (MITR) is a switch that promotes osteogenesis and inhibits adipogenesis of mesenchymal stem cells by inactivating peroxisome proliferator-activated receptor gamma-2.

EZH2, a catalytic subunit of Polycomb-repressive complex 2 (PRC2), is a histone lysine methyltransferase that methylates lysine 27 of histone H3, resulting in gene silencing. It has been shown that EZH2 plays a pivotal role in fostering self-renewal and inhibiting the differentiation of embryonic stem cells. Mesenchymal stem cells (MSCs) can be induced to differentiate into adipogenic and osteogenic lineages, which are mutually exclusive. However, it is not clear whether the molecular events of EZH2-mediated epigenetic silencing may coordinate differentiation between osteoblasts and adipocytes. Disruption of the balance between adipogenesis and osteogenesis is associated with many diseases; thus, identifying a switch that determines the fate of MSC is critical. In this study, we used EZH2-ChIP-on-chip assay to identify differential EZH2 targets in the two differentiation stages on a genome-wide scale. After validating the targets, we found that myocyte enhancer factor-2 interacting transcriptional repressor (MITR)/HDAC9c was expressed in osteoblasts and greatly decreased in adipocytes. We demonstrated that MITR plays a crucial role in the acceleration of MSC osteogenesis and attenuation of MSC adipogenesis through interaction with peroxisome proliferator-activated receptor (PPAR) γ-2 in the nucleus of osteoblasts, which interrupts PPARγ-2 activity and prevents adipogenesis. Together, our results demonstrated that MITR plays a master switch role to balance osteogenic and adipogenic differentiation of MSCs through regulation of PPARγ-2 transcriptional activity.