[Role of endoplasmic reticulum stress-mediated glycogen synthase kinase 3ß activity in pathogenesis of acute liver failure in mice].

Objective: To study the role of endoplasmic reticulum (ER) stress-mediated glycogen synthase kinase 3ß (GSK3ß) activity in the pathological process of liver injury in acute liver failure (ALF) mice. Methods: ALF model was established by intraperitoneal injection of D-galactosamine/lipopolysaccharide (D-GalN/LPS) in C57BL/6 mice. The mice were divided into control group (n=10), ALF model group (n=18), 4-phenylbutyrate (4-PBA, an ER stress inhibitor) group (n=18) and SB216763 (a specific inhibitor of GSK3ß) group (n=16). The serum alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured to reflect the liver function, liver injury was assessed by observing pathological changes of liver tissue, the levels of proteins in liver tissue were analyzed by Western blotting, the activity of GSK3ß in liver tissue was detected using GSK3ß activity assay kit, and the survival rate of hepatocyte was measured by methyl thiazolyl tetrazolium (MTT) assay. Results: In in vivo experiment, the expression levels of ER stress markers, glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP), were upregulated during the progression of D-GalN/LPS-induced ALF, indicating activation of severe ER stress and increased activity of GSK3ß. Compared with the model group, inhibition of ER stress by 4-PBA improved liver function[ALT: (365.4±58.6) U/L vs (1 094.5±201.5) U/L, P<0.05; AST: (555.1±60.8) U/L vs (1 444.3±533.7) U/L, P<0.05)and pathological injury, also decreased the activity of GSK3ß (2.6±0.3 vs 4.6±1.3, P<0.05). Inhibition of GSK3ß activity was shown to alleviate liver injury in ALF by reducing the expression levels of GRP78 and CHOP. The in vitro experiment of tunicamycin-induced hepatocyte apoptosis showed that inhibition of GSK3ß activity increased the cell survival rate. Conclusion: In ALF induced by D-GalN/LPS, severe ER stress may accelerate the development and progress of ALF by upregulating the activity of GSK3ß.

Pilot study of DNA methylation in the pathogenesis of chronic rhinosinusitis with nasal polyps.

BACKGROUND: DNA methylation has been implicated in the pathogenesis of allergy and atopy. This study aimed to identify whether DNA methylation also plays an important role in the pathogenesis of nasal polyps (NP). METHODOLOGY: NP tissues were obtained from 32 patients with chronic rhinosinusitis with bilateral NP. Biopsies of inferior turbinate mucosa (ITM) were taken from 18 patients who underwent rhinoseptoplasty (control group). The methylated genes, which were detected by DNA methylation microarray, were validated by methylation-specific polymerase chain reaction, bisulphite sequencing, real-time polymerase chain reaction and immunohistochemistry. RESULTS: DNA methylation microarray identified 8,008 CpG islands in 2,848 genes. One hundred and ninety-eight genes were found to have a methylated signal in the promoter region in NP samples compared with ITM samples. The four top genes that changed, COL18A1, EP300, GNAS and SMURF1, were selected for further study. The methylation frequency of COL18A1 was significantly higher in NP samples than in ITM samples. CONCLUSIONS: DNA methylation might play an important role in the pathogenesis of NP. Promoter methylation of COL18A1 was found to be significantly increased in NP tissues, further studies are necessary to confirm the significance of these epigenetic factors in the mechanisms underlying the development or persistence of NP.

[Nasopharyngeal low grade papillary adenocarcinoma with squamous differentiation：a case report].

Summary Low grade papillary adenocarcinoma is especially rare tumor in nasopharynx. Here we reported a patient who had low grade papillary adenocarcinoma of the nasopharynx and was diagnosed by pathology. The patient complained for bilateral nasal congestion for 10 years and was hospitalized in recent 3 years. The patient received nasopharyngeal tumor resection, and the postoperative pathological examination showed low grade nasopharyngeal papillary adenocarcinoma with squamation. The patient was followed up for 9 months without recurrence or metastasis. We reported this case and reviewed the relevant literature in order to improve the diagnosis and treatment of this disease..

The adhesion of putative probiotic lactobacilli to cultured epithelial cells and porcine intestinal mucus.

AIMS: To investigate the adhesion of lactobacilli and their subsequent competitive exclusion ability against pathogens. METHODS AND RESULTS: Four species of putative probiotic lactobacilli were studied for their adhesion abilities. First, the adhesion to Caco-2 cells was examined by light and electron microscopy. The four species were then labelled by [methyl-(3)H] thymidine and their adhesion to porcine intestinal mucus was determined by radioactivity. The tested lactobacilli showed best adhesion on ileal mucus compared with duodenal and jejunal mucus. Oxidative compound pre-treatment (NaIO(3) and NaIO(4)) dramatically decreased the adhesion of the lactobacilli to mucus. Pre-treating mucus with proteolytic enzymes (proteinase K and trypsin) resulted in the increase of adhesion in Lactobacillus serotype Reuteri I2021, but the results in the other species were variable. Lactobacillus serotype Fermentum I5007 showed greatest adhesion potential and exerted the best competitive exclusion against Salmonella and Escherichia. CONCLUSIONS: Adhesion ability in lactobacilli is species-specific. Lactobacilli with higher adhesion index have better competitive exclusion ability. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that there is a positive correlation between adhesion and competitive exclusion ability of lactobacilli. Additionally, the in vitro adhesion assay is a feasible way to screen unknown lactobacilli, potentially for future industrial applications.