Stimulating mechanism of corn oil on biomass and polysaccharide production of Pleurotus tuber-regium mycelium.

Hyperbranched polysaccharides (HBPSs) are the main components in cell wall and exopolysaccharide (EPS) of Pleurotus tuber-regium. To enhance the yield of these macromolecules, corn oil at 4% addition exhibited the best effect for production of mycelial biomass at 20.49 g/L and EPS at 0.59 g/L, which was 2.56 folds and 1.90 folds of the control, respectively. The treated hyphae were much thicker with smooth surface, while its cell wall content (43.81 ± 0.02%) was 1.96 times of the control (22.34 ± 0.01%). Moreover, a large number of lipid droplets could be visualized under the view of confocal laser scanning microscopy (CLSM). RNA-seq analysis revealed that corn oil could enter the cells and result in the up-regulation of genes on cell morphology and membrane permeability, as well as the down-regulation on expression level of polysaccharide hydrolase and genes involved in the MAPK pathway, all of which probably contribute to the increase of polysaccharides production.

CTC clusters induced by heparanase enhance breast cancer metastasis.

Aggregated metastatic cancer cells, referred to as circulating tumor cell (CTC) clusters, are present in the blood of cancer patients and contribute to cancer metastasis. However, the origin of CTC clusters, especially intravascular aggregates, remains unknown. Here, we employ suspension culture methods to mimic CTC cluster formation in the circulation of breast cancer patients. CTC clusters generated using these methods exhibited an increased metastatic potential that was defined by the overexpression of heparanase (HPSE). Heparanase induced FAK- and ICAM-1-dependent cell adhesion, which promoted intravascular cell aggregation. Moreover, knockdown of heparanase or inhibition of its activity with JG6, a heparanase inhibitor, was sufficient to block the formation of cell clusters and suppress breast cancer metastasis. Our data reveal that heparanase-mediated cell adhesion is critical for metastasis mediated by intravascular CTC clusters. We also suggest that targeting the function of heparanase in cancer cell dissemination might limit metastatic progression.

Macrophage migration inhibitory factor promotes tumor aggressiveness of esophageal squamous cell carcinoma via activation of Akt and inactivation of GSK3ß.

The pleiotropic pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), represents an important link between chronic inflammation and tumorigenesis. Although accumulating evidence demonstrates that MIF overexpression is implicated in the development and progression of multiple cancers, including esophageal squamous cell carcinoma (ESCC), the molecular mechanisms underlying its tumor-promoting roles in ESCC remain unclear. In the present study, we observed that MIF is overexpressed in ESCC and correlated significantly with lymph node metastasis, advanced clinical stage, and poor survival of ESCC. MIF knockdown attenuated the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Moreover, blockage of MIF expression decreased the activation of the Akt, MEK/ERK, and NF-κB pathways and enhanced sensitivity to apoptosis. Meanwhile, repression of MIF expression resulted in activation of glycogen synthase kinase 3 beta (GSK3ß) and subsequent decrease of active ß-catenin, as well as its downstream targets including cyclin D1, matrix metalloproteinase (MMP)-7, c-myc, and c-Jun. Collectively, our results provided mechanistic insights into the tumor-promoting role of MIF in ESCC, and suggested that MIF represents a potential therapeutic target for treatment of ESCC.

Molecular mechanisms of the analgesic action of Wu-tou Decoction on neuropathic pain in mice revealed using microarray and network analysis.

Wu-tou Decoction (WTD) is a classic herbal formula in traditional Chinese medicine for the treatment of joint diseases, neuropathic pain (NP) and inflammatory pain. In this study we investigated whether WTD produced analgesic action in a mouse spinal nerve ligation (SNL) model and elucidated the underlying molecular mechanisms. Mice were subjected to SNL and orally treated with WTD (3.15, 6.30 or 12.60 g·kg-1·d-1) for 21 d. SNL induced mechanical hyperalgesia and heat hyperalgesia characterized by rapid and persistent pain hypersensitivity. In addition, the expression levels of IL-1ß, TNF-α, CCL2 and CXCL1 in the spinal cord dorsal horn were dramatically increased on the 10th d post-surgery. Oral administration of WTD dose-dependently suppressed both mechanical and heat hyperalgesia as well as the expression levels of inflammatory cytokines in the spinal cord dorsal horn on the 21st d post-surgery. Then whole-genome microarray analyses were conducted to detect the gene expression profiles of spinal cord dorsal horn in SNL mice with or without WTD treatment. After construction of the WTD-SNL-network and topological analysis, a list of candidate target genes of WTD acting on SNL-induced NP was identified and found to be functionally enriched in several glial cell activation-related pathways and neuroinflammatory pathways. Our data have clarified the gene expression patterns in the mouse spinal cord under the NP condition. We also demonstrate the analgesic action of WTD through suppression of glial cell activation and neuroinflammation, which suggest the potential of WTD as a promising candidate for the treatment of NP.