Randomized double-blind clinical trial of Moluodan () for the treatment of chronic atrophic gastritis with dysplasia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of Moluodan () in treating dysplasia in chronic atrophic gastritis (CAG) patients.</p><p><b>METHODS</b>This was a multi-centered, double-blind, randomized controlled trial. The total of 196 subjects were assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked randomization. Mucosa marking targeting biopsy (MTB) was used to insure the accuracy and consistency between baseline and after 6-month treatment. Primary outcomes were histological score, response rate of pathological lesions and dysplasia disappearance rate. Secondary endpoints included gastroscopic findings, clinical symptom and patient reported outcome (PRO) instrument.</p><p><b>RESULTS</b>Dysplasia score decreased in Moluodan group (P =0.002), significance was found between groups (P =0.045). Dysplasia disappearance rates were 24.6% and 15.2% in Moluodan and folic acid groups respectively, no significant differences were found (P =0.127). The response rate of atrophy and intestinal metaplasia were 34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan could improve erythema (P =0.044), and bile reflux (P =0.059), no significance between groups. Moluodan was better than folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite (P <0.05), with symptom disappearance rates of 37% to 83%.</p><p><b>CONCLUSIONS</b>Moluodan improved dysplasia score in histopathology, and erythema and bile reflux score in endoscopy, and superior to folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite. [ChiCTR-TRC-00000169].</p>

Effect of BRMS1 expression on proliferation, migration and adhesion of mouse forestomach carcinoma

OBJECTIVE@#To discuss the effect of BRMS1 on the proliferation, migration and adhesion of mouse forestomach carcinoma.@*METHODS@#The constructed pCMV-myc-BRMS1 recombinant plasmid and blank plasmid were transfected into mouse forestomach carcinoma. MTT method was employed to measure the activity of gastric cancer cell; the scratch assay and Transwell assay to measure the migration and invasion of gastric cancer cell; the adhesion assay to measure the adhesion of gastric cancer cell; while the Western blot assay to measure the expression of The NF-κB signal pathway, downstream matrix metalloproteinase (MMP)-2, MMP-9 and osteopontin and E-cadherin in the gastric cancer cell. Besides, the transplanted animal model of gastric cancer in mice was constructed to measure the size of tumor xenograft.@*RESULTS@#Results of MTT assay showed that, compared with the empty vector control group, the activity of gastric cancer cell was not affected in the BRMS1 transfection group. The improved expression of BRMS1 could inhibit the adhesion, migration and invasion of gastric cancer cell (P < 0.01). Besides, compared with the empty vector control group, the phosphorylation of NF-κB p65 and IκBα was reduced in the BRMS1 transfection group, with the decreased expression of MMP-2, MMP-9 and osteopontin and the increased expression of E-cadherin (P < 0.01). Results of animal experiment also showed that the expression of BRMS1 did not affect the transplanted tumor.@*CONCLUSIONS@#The expression of BRMS1 can significantly inhibit the adhesion, migration, invasion and metastasis of mouse forestomach carcinoma gastric cancer cell, which is related to The NF-κB signal pathway.

Effect of BRMS1 expression on proliferation, migration and adhesion of mouse forestomach carcinoma

Objective: To discuss the effect of BRMS1 on the proliferation, migration and adhesion of mouse forestomach carcinoma. Methods: The constructed pCMV-myc- BRMS1 recombinant plasmid and blank plasmid were transfected into mouse forestomach carcinoma. MTT method was employed to measure the activity of gastric cancer cell; the scratch assay and Transwell assay to measure the migration and invasion of gastric cancer cell; the adhesion assay to measure the adhesion of gastric cancer cell; while the Western blot assay to measure the expression of The NF-κB signal pathway, downstream matrix metalloproteinase (MMP)-2, MMP-9 and osteopontin and E-cadherin in the gastric cancer cell. Besides, the transplanted animal model of gastric cancer in mice was constructed to measure the size of tumor xenograft. Results: Results of MTT assay showed that, compared with the empty vector control group, the activity of gastric cancer cell was not affected in the BRMS1 transfection group. The improved expression of BRMS1 could inhibit the adhesion, migration and invasion of gastric cancer cell (P < 0.01). Besides, compared with the empty vector control group, the phosphorylation of NF-κB p65 and IκBα was reduced in the BRMS1 transfection group, with the decreased expression of MMP-2, MMP-9 and osteopontin and the increased expression of E-cadherin (P < 0.01). Results of animal experiment also showed that the expression of BRMS1 did not affect the transplanted tumor. Conclusions: The expression of BRMS1 can significantly inhibit the adhesion, migration, invasion and metastasis of mouse forestomach carcinoma gastric cancer cell, which is related to The NF-κB signal pathway.

Protective effect and mechanism of hepcidin in rats with alcoholic liver damage / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the mechanism of how iron-regulatory protein (hepcidin) affect iron overload in alcoholic liver disease (ALD).</p><p><b>METHODS</b>Thirty male wistar rats were randomly divided into 3 groups: Lieber-Decarli liquid without alcohol group (control group), Lieber-Decarli liquid with alcohol (alcohol group) and hepcidin intraperitoneally injected group (hepcidin group), each rat was fed for 6 weeks. The Serum concentration of Alanine Aminotransferase (ALT), Aspartate Amino Transferase (AST), Iron, Total Iron Binding capacity (TIBC), Ferritin, Malonyl Dialdehyde (MDA) and Hepcidin were determined. Hepatic tissue was examined by hematoxylin and eosin staining, prussian blue iron staining and immunohistochemistry staining.</p><p><b>RESULTS</b>(1) Serum concentration of ALT in control group, alcohol group and hepcidin group were (25.2 ± 4.6) U/L, (37.9 ± 14.3) U/L and (40.9 ± 14.1) U/L (F = 4.907, P < 0.05), respectively. Serum AST among three groups were (32.3 ± 13.4) U/L, (55.0 ± 18.6) U/L and (48.3 ± 26.0) U/L (F = 3.742, P < 0.05), respectively. The secretions of ferritin were (224.72 ± 85.49) ng/ml, (345.59 ± 124.75) ng/ml and (339.47 ± 138.47) ng/ml (F = 3.539, P < 0.05). The serum concentrations of TIBC were (147.30 ± 31.98) μmol/L, (148.04 ± 58.74) μmol/L and (143.28 ± 37.38) μmol/L (F = 1.209, P > 0.05), respectively. The serum concentrations of iron were (55.64 ± 13.32) μmol/L, (60.37 ± 25.89) μmol/L and (49.77 ± 17.64) μmol/L (F = 0.651, P > 0.05), respectively. The serum concentration of MDA were (5.84 ± 2.17) nmol/ml, (6.51 ± 2.23) nmol/ml and (4.27 ± 2.68) nmol/ml (F = 2.782, P > 0.05), respectively. The serum concentration of Hepcidin were (155.96 ± 44.91)ng/ml, (124.11 ± 31.98) ng/ml and (114.96 ± 25.81) ng/ml (F = 3.839, P < 0.05), respectively. (2) Significant fat change observed in the liver of alcohol group. The positive granulations of iron staining were (0.8 ± 1.0), (1.2 ± 1.6) and (1.1 ± 1.1) (F = 0.254, P > 0.05), respectively. No differences found of liver iron express among the three groups. Intraperitoneal injection of hepcidin increased hepcidin expression in liver which was inhibited by alcohol (F = 4.139, P < 0.05).</p><p><b>CONCLUSIONS</b>ALD rats with lower hepcidin expression in liver can result in iron metabolism disorder. Ectogenic hepcidin can protect liver against alcohol damage by inhibiting lipid peroxidation.</p>

Stimulation of human hepatic stellate cells by cytochrome P4502E1-mediated oxidative stress / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the stimulation of human hepatic stellate cells by Cytochrome P4502E1-mediated oxidative stress.</p><p><b>METHODS</b>HepG2-line was transfected with human CYP2E1 plasmid (HepG2/CYP2E1) and empty plasmid (HepG2/PCI) respectively. The CYP2E1 expression was evaluated with RT-PCR and Western blot. MDA was measured in culture medium of HepG2 cell lines. LX2 was co-incubated with HepG2/CYP2E1, HepG2/PCI and HepG2 respectively. The level of hydroxyproline in culture medium was examined in 48 hours and the cells were lysated and total RNA and protein were extracted. COL-1 and MMP2 mRNA levels were detected by RT-PCR and analyzed semi-quantitatively. PICP proteins were measured by ELISA. Zymography was performed to investigate MMP2 enzymatic activities.</p><p><b>RESULTS</b>(1) MDA from the HepG2 which (HepG2/CYP2E1)express human CYP2E1 (6.51+/-0.25) was significantly higher than that from the HepG2 which do not (HepG2/PCI) express human CYP2E1 (3.07+/-0.29) and HepG2 alone (2.57+/-0.29). (F=22.66, all P<0.01). (2) After co-incubated for 48 hours,the level of hydroxyproline in culture medium (35.24+/-3.52) excreted from CYP2E1/LX2 could significantly increase (F=58.89, P is less than 0.01). PICP protein (540.01+/-11.38) excreted from CYP2E1/LX2 was significantly increased (F=124.97, P<0.01). Zymography showed MMP2 gene expression and enzymatic activities of MMP2 had no difference among the groups (F=0.29, P>0.05) (F=0.33, P>0.05).</p><p><b>CONCLUSIONS</b>CYP2E1 derived oxidative stress mediated stimulation of collagen I synthesis by hepatic stellate cells. Hydroxyproline excreted by LX2 was increased by CYP2E1. COL-1mRNA had no difference among the groups (F=0.73, P>0.05).</p>