[Design, synthesis and biological evaluation of novel [1,3] dioxolo [4,5-f]isoindolone derivatives].

A series of [1,3]dioxolo[4,5-f]isoindolone derivatives were designed, synthesized and evaluated as inhibitors of acetylcholinesterases (AChE). Furthermore, their effects on memory impairment of mice induced by scopolamine were investigated with step-through test. The results suggested that most of the target compounds exhibited potential inhibition on AChE with IC50 values at micromolar range. Compounds I1 (IC50 value of 0.086 µmol · L(-1)) and I2 (IC50 value of 0.080 µmol · L(-1)) showed the strongest AChE inhibitory activity, which are equipotent to donepezil (IC50 value of 0.094 µmol · L(-1)). Moreover, compounds I1-I4 could improve the memory impairment induced by scopolamine in mice.

[Roles of bile and gastrin in the pathogenesis of childhood gastroesophageal reflux disease].

OBJECTIVE: To explore the incidence of acid and bile reflux in children with gastroesophageal reflux disease (GERD) and to study the roles of bile and gastrin in the pathogenesis of childhood GERD. METHODS: Forty-two cases of GERD were divided into two groups according to endoscopic findings: reflux esophagitis (RE) and non-erosive reflux disease (NERD). The patients underwent 24-hr ambulatory esophageal pH and bilirubin monitoring. The serum concentration of gastrin was detected by radioimmunoassay. Thirteen children without gastroesophageal reflux symptoms, digestive tract disease and severe systemic organic disease served as the Control group. RESULTS: Of the 42 cases of GERD, 24 cases were confirmed with RE, with esophageal mucosal lesions, and 18 were NERD without esophageal mucosal lesions by endoscopy. Both acid and bile reflux parameters, including the percentage of total time with pH < 4 and bilirubin absorbance >/= 0.14, the total number of reflux episodes and the number of bile reflux episodes lasting longer than 5 minutes, were significantly higher in the GERD patients than those in the Control group (P < 0.05). The time of esophageal acid exposure (pH < 4) and the percentage of total time with bilirubin absorbance >/= 0.14 increased significantly in the RE group compared with in the NERD group (P < 0.05). Sixteen RE patients had a mixed reflux of bile and acid (66.7%) but only 6 NERD patients (33.3%) had (P < 0.01). The serum concentration of gastrin in the RE group (125.12 +/- 45.06 pg/mL) and the NERD group (98.22 +/- 27.92 pg/mL) was significantly higher than that of the Control group (74.22 +/- 20.34 pg/mL) (P < 0.01, P < 0.05 respectively). A significant difference was noted in the serum concentration of gastrin between the RE and the NERD groups (P < 0.05). CONCLUSIONS: Mixed reflux of bile and acid are common in children with GERD. Bile reflux may play a role in the development of GERD. Gastrin parasecretion may participate in the development of GERD. Gastrin and bile reflux may have synergistic effects on the development of childhood GERD.

[Expression of proliferating cell nucleus antigen and nm23 protein and their relation with metastasis in hepatocellular carcinoma].

OBJECTIVE: To investigate the expression of proliferating cell nucleus antigen (PCNA) and nm23 protein in hepatocellular carcinoma (HCC) and their relation with metastasis. METHODS: The expression of PCNA and nm23 protein in 56 HCCs were detected by the immunohistochemical technique. RESULTS: Of the 56 HCCs, the expression strength of PCNA and nm23 protein were significantly related to the differentiation degree of HCC: the poorer the differentiation of HCC, the stronger the PCNA expression, and the weaker the nm23 protein expression. The correlation analysis indicated that the strength of the PCNA expression was negatively related to that of nm23 (P < 0.01). The intensity of PCNA expression in HCCs with metastasis was significantly higher than that in HCCs without metastasis (P < 0.01), which was inverse with nm23 protein (P < 0.01). CONCLUSION: The level of PCNA and nm23 protein may reflect the differentiation degree and metastasis potential of HCC, and may be one of the useful parameters for judging prognosis of HCC.

[Significance of phosphorylation of mitogen-activated protein kinase and signal transducer and activator of transcription 3 and cyclin D1 protein expression in Hodgkin's lymphomas].

BACKGROUND & OBJECTIVE: Signal cascades of mitogen-actived protein kinase(MAPK) and signal transducer and activator of transcription 3 (Stat3) are two main signal transduction pathways which were associated with cell proliferation and malignant transformation.MAPK and Stat3 proteins are activated by phosphorylation. The biological effects which are caused by multiple cytokines produced by Hodgkin's lymphoma(HL) cells are mediated through MAPK and Stat3 signal pathways. This study was designed to investigate significance of MAPK and Stat3 phosphorylation(p-MAPK and p-Stat3) and cyclin D1 protein expression in HL. METHODS: SP immunohistochemistry was used to detect expression of p-MAPK, p-Stat3, and cyclin D1 protein in 45 cases of HL of various types. RESULTS: The expression positive rates of p-MAPK, p-Stat3, and cyclin D1 proteins were 73.3%(33/45),64.4%(29/45), and 68.9%(31/45), respectively. The positive expression levels of p-MAPK and cyclin D1 protein gradually increased(P< 0.05), whereas that of p-stat3 had no significant difference(P >0.05) in four subsets(LR:lymphocyte-rich classical type; NS:nodular sclerosis type; MC:mixed cellularity type; LD:lymphocyte depletion type) of all cases. The expression of p-MAPK was positively related to that of cyclin D1 protein (r(s)=0.7254,P< 0.01), but the expression of p-Stat3 was not related to that of cyclin D1 protein (r(s)=0.2197,P >0.05). CONCLUSION: The data suggest that activation of MAPK may play an important role in genesis and progression of HL, but Stat3 activation is not associated with the progression of HL. MAPK may induce overexpression of cyclin D1 protein and results in persistent proliferation of RS/H cells in genesis and development of HL.