Expression and clinical implication of S100A12 in gastric carcinoma.

S100 protein family has been implicated in multiple stages of tumorigenesis and progression in which S100A12 is one of the subtypes. However, the role of S100A12 in gastric carcinoma (GC) has not been elucidated yet. This study was aimed to investigate the expression of S100A12 in GC tissues and evaluate the clinical significance of S100A12 in GC patients. S100A12 protein was detected in 207 GC and 52 paired non-cancerous mucosal tissues by immunohistochemistry, while messenger RNA (mRNA) was investigated by Oncomine database analysis. Moreover, survival analysis was performed and the correlation between S100A12 and ubiquitin-specific protease 10 (USP10) and p53 was determined. As for tumor cells, the expression of S100A12 protein and mRNA in GC was proved to be lower than that in non-cancerous mucosa tissues (p < 0.05). Clinicopathological analysis showed that S100A12 protein was negatively associated with tumor size (p = 0.004), depth of invasion (p = 0.022), tumor node metastasis (TNM) stage (p = 0.018), Lauren classification (p < 0.000), and cell differentiation (p < 0.000). In contrast, a positive correlation was found between S100A12 and USP10 protein (p < 0.000). However, no relationship was detected between S100A12 and p53. Moreover, the survival analysis indicated that S100A12 protein was a favorable factor of prognosis of GC (p < 0.05). Although the expression of S100A12 in the stromal cells was detected higher than that in the tumor cells, no relationship between S100A12 protein in stromal cells and the clinicopathological features described above was found (p > 0.05). Our findings suggested that low expression of S100A12 might be served as a new marker in the tumorigenesis and progression of GC.

Fabrication of Alginate/Calcium Carbonate Hybrid Microparticles for Synergistic Drug Delivery.

A hybrid drug delivery system coloaded with different drugs for synergistic drug delivery was developed. Alginate/calcium carbonate (CaCO3) hybrid microparticles (MPs) were fabricated via a facile coprecipitation method under mild conditions without using any organic solvent and surfactant. Due to the incorporation of negatively charged alginate chains onto the surface, the obtained hybrid MPs with spherical morphology showed good colloidal stability in an aqueous solution. An antitumor drug (doxorubicin, DOX) and a drug resistance reversal agent (verapamil, VP) were coloaded in the hybrid MPs simultaneously to obtain dual-drug-loaded MPs (DOX/VP/MP). Due to the presence of inorganic CaCO3 (∼54 wt%), the drugs could be loaded in the hybrid MPs with high encapsulation efficiency and the drug release could be effectively sustained. The cell growth inhibition of the drug-loaded MPs was evaluated in HeLa cells. An in vitro study showed DOX/VP/MP exhibited higher cell growth inhibition as compared with DOX monodrug-loaded MPs (DOX/MP). These results suggest the hybrid MPs can potentially be used as a synergistic drug delivery platform for cancer chemotherapy.

Betaine protects against high-fat-diet-induced liver injury by inhibition of high-mobility group box 1 and Toll-like receptor 4 expression in rats.

BACKGROUND AND OBJECTIVES: Previous studies have shown that betaine prevents alcohol-induced liver injury and improves liver function. The purpose of this study was to investigate the hepatoprotective effects of betaine on nonalcoholic fatty liver disease (NAFLD) and to observe changes of HMGB1/TLR4 signaling. METHODS: Thirty rats were randomly divided into control, model, and betaine groups. The rats in the model and betaine groups were fed a high-fat diet for 12 weeks to induce an animal model of NAFLD. The rats in the betaine group were then intragastrically administered betaine solution at a dose of 400 mg/kg per day for four weeks. Liver histology was examined. Serum levels of ALT, AST, TC, TG, HDL-C, LDL-C, FFA, HMGB1, NF-κB, TLR4, and tHcy were determined and intrahepatic TC, TG, and Hcy levels were assayed. mRNA expression and protein levels of HMGB1, NF-κB, and TLR4 in liver tissue were also determined. RESULTS: Compared with the control group, rats in the model group developed severe liver injury, accompanied by significant increases in serum levels of ALT, AST, TC, TG, LDL-C, FFA, HMGB1, NF-κB, and TLR4, intrahepatic TC, TG, and Hcy content, histological scores for steatosis, inflammation, and necrosis, and mRNA expression and protein levels of HMGB1, NF-κB, and TLR4, and a significant decrease in serum HDL-C (P < 0.05). Compared with the model group, all these indicators were significantly improved by administration of betaine (P < 0.05). CONCLUSIONS: Betaine effectively protects against high-fat-diet-induced NAFLD and improves liver function; the mechanism is probably related to inhibition of HMGB1/TLR4 signaling pathways.

Two new geranylphenylacetate glycosides from the barks of Cinnamomum cassia.

Two new glycosides, cinnacassides F (1) and G (2), with a rare geranylphenylacetate carbon skeleton, were isolated from the barks of Cinnamomum cassia, along with three known analogues, cinnacassides A (3), B (4) and C (5). The structures of the new compounds were elucidated on the basis of extensive NMR spectroscopic analyses and chemical method. Compounds 1-5 were investigated for their immunomodulatory activities, and compounds 1, 3 and 4 showed differential immunosuppressive activities against murine lymphocytes.

In situ formation of thermosensitive PNIPAAm-based hydrogels by Michael-type addition reaction.

To investigate the possibility of in situ thermosensitive hydrogel formation via Michael-type addition reaction, we designed and prepared thiol- and vinyl-modified poly(N-isopropylacrylamide) (PNIPAAm)-based copolymers. When the solutions of these two kinds of PNIPAAm-based copolymers were mixed at physiological temperature (37 degrees C), a physical gelation resulting from the hydrophobic aggregation of PNIPAAm based copolymers and chemical cross-linking between thiol and vinyl functional groups or so-called chemical gelation occurred, resulting in the formation of a three-dimensional hydrogel. Because all the gelations were performed at a high temperature (above LCSTs of the PNIPAAm based copolymers), these in situ formed hydrogels presented heterogeneous network structures, resulting in an improved thermosensitivity in comparison with the conventional one.