This study demonstrates, for the first time, that SHIP2 is frequently downregulated in gastric cancer, and reduced SHIP2 expression promotes tumorigenesis and proliferation of gastric cancer via activation of the PI3K/Akt signaling.
Past studies have shown that the Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is commonly downregulated in gastric cancer, which contributes to elevated activation of PI3K/Akt signaling, proliferation and tumorigenesis of gastric cancer cells. However, the mechanisms underlying the reduced expression of SHIP2 in gastric cancer remain unclear. While gene copy number variation analysis and exon sequencing indicated the absence of genomic alterations of SHIP2, bisulfite genomic sequencing (BGS) showed promoter hypomethylation of SHIP2 in gastric cancer cells. Analysis of transcriptional activity of SHIP2 promoter revealed Specificity protein 1 (Sp1) was responsible for the regulation of SHIP2 expression in gastric cancer cells. Furthermore, Sp1 expression, but not Sp3, was frequently downregulated in gastric cancer compared with normal gastric mucosa, which was associated with a paralleled reduction in SHIP2 levels in gastric cancer. Moreover, overexpression of Sp1 inhibited cell proliferation, induced apoptosis, suppressed cell motility and invasion in gastric cancer cells in vitro, which was, at least in part, due to transcriptional activation of SHIP2 mediated by Sp1, thereby inactivating Akt. Collectively, these results indicate that decreased expression of transcription factor Sp1 contributes to suppression of SHIP2 in gastric cancer cells.
Leaf epidermal characteristics are important for phylogenetic and taxonomic studies of many plants, but there is currently insufficient such data for this application in Zingiber species. Therefore, the leaf epidermal micromorphology of 22 species in three sections of Zingiber was investigated by light microscopy and scanning electron microscopy. Differences between various taxonomic groups of Zingiberaceae were also compared to assess their phylogenetic and taxonomic significance. As in other genera of Zingiberaceae, the epidermal cells in both the adaxial and abaxial epidermis of Zingiber species were found to be hexagonal or polygonal, with non-sinuous anticlinal walls that are arranged parallel to leaf veins. Tetracytic stomata are mostly randomly distributed in the intercostal regions of both surfaces and are more common on the abaxial surface. The stomatal density of the species in sect. Pleuranthesis is significantly lower than that in sects. Zingiber and Cryptanthium. There are two types of trichome in Zingiber: so-called “delicate” trichomes are present in most species, while “stout” trichomes with a swollen base are only found in Z. corallinum and Z. montanum. Oil cells occur in both epidermal layers of some species in sects. Zingiber and Cryptanthium, but only in the abaxial epidermis of Z. ellipticum in sect. Pleuranthesis. Crystals are found in the abaxial epidermis only in all species, but are present in both epidermal layers of Z. corallinum and Z. montanum. Although the epidermal morphology is similar in most Zingiber species, stomatal density, type of trichome and distribution of oil cells and crystals offer valuable information for the systematic and taxonomic studies in this genus.
The improvement of the solid content of the hydrophobic drugs (such as paclitaxel (PTX), etc.) loaded nanoparticles (NPs) dispersion is important for enhancing drug-loaded efficiency and reducing the cost in production and application. A diblock copolymer methoxy poly(ethylene glycol)-b-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (mPECT) is synthesized via the ring-opening polymerization of ε-caprolactone and 1,4,8-trioxa[4.6]spiro-9-undecanone (TOSUO) with methoxy poly(ethyleneglycol) (mPEG) as the initiator. The chemical structures and thermal properties of mPECT are characterized by (1)HNMR, Fourier transform infrared (FT-IR), gel permeation chromatography, differential scanning calorimetry, etc. PEG45.45-b-P(C28.33-co-T5.38) (mPECT-2) is able to self-assemble into stable NPs in water via nanoprecipitation method at a high solid content (≤25 wt%) and their freeze-dried powders can well re-disperse in water. The paclitaxel (PTX) is chosen as a hydrophobic drug model and successfully encapsulate into the mPECT-2 NPs via the same method at a high solid content. The encapsulation efficiency, cytotoxicity and in vitro release of PTX-loaded NPs are investigated. The results suggest that the behavior of the drug-loaded mPECT-2 NPs prepared at a solid content of 25 wt% is similar to that of NPs prepared at a solid content of 1 wt%, which indicate that increasing solid content of polymer has no negative effect on the properties of NPs dispersion in application. In summary, the freeze-dried NPs prepared from the high solid content dispersion (≤25 wt%) has a good redispersibility and exhibits great potential in cost control of preparing NPs dispersion used as drug delivery system.
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