ABSTRACT
Objective Glucagon-like peptide-1 (GLP-1) has been reported to be effective in the treatment of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanism of GLP-1 on NAFLD is remained unclear. The present study was to detect whether the effect of GLP-1 on triglyceride (TG) content in hepatocytes is dependent on Foxos. Methods HepG2 cells were treated with palmitic/oleic acid for 24 h. The knockdown of Foxo1, Foxo3 was conducted through small interfering RNA (siRNA). Real time PCT (RT-PCR) was used to detect the changes of the SREBP1c and Acox2 genes in HepG2 cells after Foxo1/3 knockdown. Results As expected, palmitic/oleic acid increased TG concentration in HepG2 cells [(12.65 ± 1.32) μg/mg vs. (4.32 ± 0.54) μg/mg, P<0.05]. Addition of GLP-1 dose (10, 50, 100nmol/L) dependently lowered the TG content and reached plateau at 100 nmol/L of GLP-1 [TG(8.38±1.47) μg/mg]. The GLP-1 effect on TG remained after knocking down either Foxo1 [(9.09±1.34)μg/mg] or Foxo3 [(8.90± 1.60) μg/mg] alone, but not when knocking down Foxo1 and Foxo3 (Foxo1/3) together [(14.66±1.77)μg/mg]. Moreover, knocking down Foxo1/3 also abolished GLP-1 effect on SREBP1c and Acox2 expression. Conclusion GLP-1 can inhibit the synthesis of TG in hepatocytes depending on Foxo1 and Foxo3. Further studies are needed to explore the specific mechanisms.
ABSTRACT
Objective To investigate the killing effect of hematoporphyrin derivative photedynamic therapy (PDT) on cultured human pancreatic cancer cell,and to explore the mechanism of this effect.Methods Biolitec PDT 630 semi-conductor laser therapeutic apparatus was used as the light source.After pancreatic cancer cell PANC1 was incubated 8 h with different concentrations of Photosan(hematoporphyrin derivative) as photosensitizer (0.5mg/L,1 mg/L,2 mg/L,4 mg/L),the cells were given different doses of 630nm laser irradiation(1 J/cm2' 5 J/cm~2,10 J/cm~2 ).The A492 value was determined in each group with MTT method.Cell apoptosis rate was detected by flow cytometry after PDT.Results There was no killing effect when no Photosan was administrated;10 J/cm~2 irradiation had killing effect on PANC1 when Photosan was administrated as 1 mg/L(0.140±0.013 vs 0.213±0.008,P＜0.05);5 and 10 J/cm~2 irradiation all had killing effect on PANC1 when Photosan was administrated as 2 mg/L (0.081±0.024 and 0.049±0.013vs 0.211±0.031,P＜0.05 and P＜0.01 );all doses of irradiation had killing effect when Photosan was administrated as 4 mg/L.There was no significant difference between 5 and 10 J/cm~2 irradiation in term of killing effect.Cell apoptosis rates with 0 or 2 or 4 mg/L Photosan and 10 J/cm~2 irradiation were(13.8±1.8) %,(40.9±1.6)%,(62.5±2.0)%,the difference was statistically significant(P＜0.05).Conclusions Photosensitizer or irradiation alone did not produce PDT effect.With certain dose of photosensitizer and irradiation,the PDT effect increased accordingly.
ABSTRACT
Objective To investigate the clinical, pathological and endoscopic features of patients with ulcerative pancolitis (PUC) and distal colitis (DUC) and their differentiations. Methods The clinical, pathological and endoscopic data of 52 patients with PUC and 97 patients with DUC were analyzed by case-control study. Results The incidence and the frequency of bloody stool in patients with PUC were both higher than those in DUC (90.38% vs. 71.13%, P
ABSTRACT
Objective To investigate the pathohistologic features and grading of biopsy mucosae and their correlation with disease severity of active ulcerative colitis(UC). Methods A prospective study was conducted in 133 patients with UC who were divided into three groups based on the degree of severity. Pathologic morphometry and grading with HE staining sections were analyzed. Results Pathologic features of active UC: there were neutrophilic leukocytes (100.0%), eosinophils (99.2%), plasmacytes(91.7%) and lymphocytes (75.2%) infiltration among mucosal epithelial cells, and lymphoid follicular formation(72.2%) and small vessels inflammation(63.9%) and focal hemorrhage(68.4%) in lamina propria. There were crypt abscesses(43.6%), glandular abnormalities (44.4%), goblet cell depletion (18.8%), epithelial cell regeneration (36.8%) , atypical hyperplasia (28.6%) and granulation tissue formation (42.9%) in mucosae. With the increase of severity of UC, there was a significant increasing incidence of small vessel inflammation, fiberoid necrosis of vessel wall, glandular abnormality, epithelial cell regeneration, atypical hyperplasia, goblet cell depletion, granulation tissue formation, fiber tissue hyperplasia, and crypt abscess. There was no significant difference of the incidence of lymphocyte hyperplasia, lymphoid follicular formation, eosinophil and plasmacyte infiltration between the groups. Mild UC was mainly characterized by the lesions of Grade Ⅰ and Ⅱ, moderate UC by those of Grade Ⅱ and Ⅲ and severe UC by those of Grade Ⅲ and Ⅳ. There were significant differences of grades among mild, moderate and severe UC. Conclusions There were some pathologic characters in active UC. The partial of markers and histological gradings can reflect the severity and activity of active UC.
ABSTRACT
0.05) before and after treatment. The rates of eosinophil infiltration: 98.2% vs. 80.4% in the mild UC (P
ABSTRACT
AIM:To investigate the preparation techniques and anti-tumor effects both in vitro and in vivo of a novel nanoparticles control-releasing preparation of 5-fluorouracil(5-FU)by intravenous injection.METHODS:With polylactic acid(PLA)as marix materials,we adopted ultrasound emulsification method to prepare PLA enveloped 5-FU nanoparticles(5-FU-NPs).Scanning electricity microscopy was used to observe the morphology of 5-FU-NPs and laser optical scattering experiment was conducted to determine its diameter distribution.The drug-carrying capacity(ratio)of the nanoparticles was determined by means of high-power liquid chromatography(HPLC)and MTT test was used to observe cytotoxicity in vitro.The anti-tumor effects were determined at different dosages,frequencies of taking drugs in vivo.RESULTS:Scanning electron microscopy showed that the 5-FU-NPs were globular particles with smooth surface in an average particle diameter of 191.9 nm with a normal distribution,and the drug-carrying capacity of 5-FU-NPs was 15.2%.5-FU-NPs had the same anti-cancer effect as unenveloped drug in vitro and showed typical dose-effect relationship.Compared to naked 5-FU,5-FU-NPs presented significant difference(P
ABSTRACT
Objective To investigate the correlations between histological grading of the mucosal biopsies, clinical appearances and endoscopies of patients with active ulcerative colitis ( AUC) , and their roles in the therapeutic outcomes. Methods To analyze the grading in pathological, endoscopic and clinical manifestations of 133 patients, and use the scores to estimate each clinical appearance. A prospective study and Spearman correlation coefficients analysis were taken in this study. Results Among 133 patients, the grading of histological, clinical and endoscopic results in grades Ⅰ ,Ⅱ , Ⅲ , andⅣwere 29,45 ,37 and 22; 85 , 39,9 and 0; 8,30,16 and 79 cases respectively. There were significant positive correlations between histological grading and the following parameters; melena ( r =0. 49, P= 0. 000) , bowel movement ( r =0. 30, P = 0.001) , ESR (r=0. 42, P =0.000) , AI(r=0.56, P=0.000) , clinical grade (r=0.52, P=0.000) endoscopic grade (r = 0. 35 , P =0. 000). And no significant negative correlation with Hb (r = -0. 13, P = 0. 125). In 68 mild and moderate cases after administered SASP for 6 weeks with clinical remission there were 16 and 19 cases with 0 grade in endoscopies and histology respectively, and in the former group 7 cases fall in histological grade I . Conclusion There was no agreement in the clinical, endoscopic and histological grades of the AUC patients. For the evaluation of therapy, the sequence of priority is histological grade, endoscopic grade, and then clinical grade.
ABSTRACT
AIM: To elucidate the pattern of 5-fluorocytosine(5-FC) induced apoptosis and its role in gene therapy for human pancreatic cancer. METHODS: The human pancreatic cancer SW1990 cells(CEA-producing) were infected with recombinant adenoviruses(Adex1CEA-prCD or Adex1CEA-prZ).Cytosine deaminase(CD) expression was examind by western blot. Apoptosis induced by 5-FC in human pancreatic cancer SW1990 cells genetically modified to express cytosine deaminase was investigated by applying electron microscopy, DNA electrophoresis and flow cytometry analysis techniques. RESULTS: The SW1990 cells infected with Adex1 CEA-prCD were treated with 5-FC at 100 ?mol?L -1 for 48 h, cell apoptosis occurred. Typical apoptosis morphological feature appeared and DNA ladder could be demonstrated on DNA electrophoresis. Apoptosis peak was also showed by flow cytometry. Apoptotic cells accounted for 34.6% of the cell population. Cells in G 1, S and G 2/M phase of cell cycle were 64%, 11% and 7%, respectively. CONCLUSION: The apoptosis induced by 5-FC may be a primary mechanism in CD gene therapy for pancreatic cancer.
ABSTRACT
AIM: To observe the effects of aspirin and prostaglandin E_2 (PGE_2) on the cell viability and cell cycle in SW1990 human pancreatic carcinoma cell lines, and to investigate the mechanisms of aspirin-induced growth inhibition and cell cycle arrest. METHODS: After incubated with aspirin or PGE_2 and their combination, the viability of SW1990 cells was measured by MTT assay. The levels of intracellular PGE_2 were determined by ELISA. The effects of aspirin or PGE_2 on cell cycle were investigated by flow cytometry (FCM). The expression of p21~ Wafl/cipl and p27~ Kipl/pic2 (the cyclin-dependent kinase inhibitors) were analyzed by Western blotting. RESULTS: Aspirin could inhibit the growth of cells and level of intracellular PGE_2 in a dose-dependent manner. Aspirin enhanced the expression of p21~ Wafl/cipl and p27~ Kipl/pic2 and induced cell cycle arrest at G_0/G_1 phase. PGE_2 increased the cell viability of SW1990 cells. However, it couldn't antagonize the changes of cell viability and cell cycle that induced by aspirin. CONCLUSIONS: The inhibitory effects of aspirin on growth and cell cycle of pancreatic carcinoma cells might not be mediated by a COX-dependent pathway completely. Cell cycle arrest induced by aspirin might be associated with up-regulation of p21~ Wafl/cipl and p27~ Kipl/pic2 .
ABSTRACT
AIM: To investigate the expression of MAT1 protein in pancreatic cancers and the relationship between MAT1 and clinicopathological features of pancreatic cancers. METHODS: 94 surgical specimens, including 70 pancreatic cancers, 10 pancreatic benign tumors, 14 chronic pancreatitis and 10 autopsy normal pancreas tissues, were analyzed immunohistochemically, and then MAT1 expression and clinicopathological features were compared. RESULTS: MAT1 was expressed mainly in the cancer cells,and also in the fibroblasts, where it was localized within the cytoplasm and nuclear envelope. MAT1 expression was found in 75.7% (53/70) of the cancers, but not detected or weakly expressed in control tissues. There was a significant difference in expression of MAT1 among the above four tissues (P