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.
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.
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.
Formal methods are vital for ensuring the security and reliability of the network systems. We propose a promising method to check security properties of cryptographic protocols using logic of events theory. The logic is designed around a message automaton with actions for possible protocol steps including generating new nonces, sending and receiving messages, and performing encryption, decryption and digital signature verification actions. We figure out types for the keys, nonces, and messages of the protocol and present novel proof rules and mechanism for protocol actions, temporal reasoning, and a specialized form of invariance rule. It puts no bound on the size of the principal and requires no state space enumeration. Our main theorem guarantees that any well-typed protocol is robustly safe under attack while reasoning only about the actions of honest principals in the protocol.
Public health awareness existed in the practice of traditional Chinese medicine (TCM) long ago. In the process of Shanghai's modernization and in competition with Western medicine, TCM in Shanghai has gradually accepted the modern public health awareness, fostering its strengths, circumventing its weaknesses and playing an important role in the local public health service. To study the vicissitude of TCM public health awareness at this time will be helpful to further understand the modern history of TCM and also provide useful reference for further participation of TCM in modern public health enterprise. In this paper, the authors used literature analysis and historical research to analyze the medical practice and writings of representative TCM practitioners, medical groups and journals. The results showed that the public health awareness of TCM in Shanghai has evolved from its traditional pattern to the modern pattern seen today; the traditional pattern was characterized by individual health care and some degree of medical collaboration, whereas the modern pattern is characterized by public health education. This process was propelled forward throughout by intense national spirit. TCM has made significant contributions to the local public health service in Shanghai in the late Qing Dynasty, which promoted the modernization of public health awareness of TCM in the People's Republic of China. The authors also found that one of the ways of modernizing TCM is to diversify the ways of publicizing TCM and make it easily understood, which can shed a new light on promoting the development of TCM.
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