The purpose of this study was to explore the role of epithelial-mesenchymal transition in the pathogenesis of hepatolithiasis. Thirty-one patients with primary hepatolithiasis were enrolled in this study. Expressions of E-cadherin, alpha-catenin, alpha-SMA, vimentin, S100A4, TGF-beta1 and P-smad2/3 in hepatolithiasis bile duct epithelial cells were examined by immunohistochemistry staining. The results showed that the expressions of the epithelial markers E-cadherin and alpha-catenin were frequently lost in hepatolithiasis (32.3% and 25.9% of cases, respectively), while the mesenchymal markers vimentin, alpha-SMA and S100A4 were found to be present in hepatolithiasis (35.5%, 29.0%, and 32.3% of cases, respectively). The increased mesenchymal marker expression was correlated with decreased epithelial marker expression. The expressions of TGF-beta1 and P-smad2/3 in hepatolithiasis were correlated with the expression of S100A4. These data indicate that TGF-beta1-mediated epithelial-mesenchymal transition might be involved in the formation of hepatolithiasis.
Adult ; *Bile Ducts/cytology/metabolism/pathology ; Biological Markers/*metabolism ; Cell Differentiation/*physiology ; Epithelial Cells/cytology/*physiology ; Epithelium/physiology ; Female ; *Gallstones/metabolism/pathology ; Humans ; Liver Diseases/metabolism/*pathology ; Male ; Mesoderm/cytology/*physiology ; Middle Aged

OBJECTIVETo observe dynamically the effect of drugs for clearing heat and removing dampness (CHRD) on biliary components in rabbits with pigment gallstones (PGS).

METHODSForty rabbits were established into PGS model and randomly divided into 3 groups, the bacterial infection group, the CHRD low-dose group and the CHRD high-dose group. Besides, a normal group was set up with healthy rabbits for control. Changes of total bilirubin (TB), unconjugated bilirubin (UCB), total bile acid (TBA), Ca2+, bacterial and endogenous beta-glucuronidase (beta-Gase) in bile were observed.

RESULTSCHRD drugs significantly decreased the contents of UCB, Ca2+, bacterial and endogenous beta-Gase (P < 0.05), and increased TBA in bile (P < 0.05).

CONCLUSIONCHRD drugs have good effect in reducing the lithogenesis of the pigment gallstones.

Animals ; Bile ; drug effects ; metabolism ; Bile Pigments ; metabolism ; Calcium ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Gallstones ; drug therapy ; metabolism ; pathology ; Glucuronidase ; metabolism ; Male ; Phytotherapy ; Rabbits ; Random Allocation ; Treatment Outcome

To observe the effect of various doses of oil of Piper longum unsaponifiable matter (OPUM) to cholesterol gallstones in experimental mice. C57BL/6 mice (n = 60) were randomly divided into 6 groups: control group, model group, OPUM (15, 30 and 60 mg x kg(-1)) group and ursodeoxycholic acid (UDCA, 60 mg x kg(-1)) group, administered for 10 weeks. The level of serum lipid and liver function enzymes were tested. The gallbladder was removed and bile was obtained by centrifugation. Next, the levels of the bile total cholesterol (TC), phospholipid (PL) and bile acid (TBA) were measured. The indicators of lipid peroxidation were determined and cholesterol saturation index (CSI) was calculated. The liver histological changes were observed by HE staining. The results showed that serum TC, TG (triglycerides) and AST (aspartate transaminase) contents, gallbladder cholesterol crystallization and CSI increased significantly (P < 0.05). In addition, the activity of SOD decreased significantly and MDA content increased significantly in liver (P < 0.05). HE staining results showed that the hepatic cord disorder and intracellular lipid droplets increased significantly. All results indicate that lithogenic diet lead to the formation of cholesterol gallstones. In OPUM (30 and 60 mg x kg(-1)) group, serum TC, TG and AST content, gallbladder cholesterol crystallization and CSI decreased significantly, the activity of SOD increased significantly and MDA content decreased significantly. HE staining results showed that OPUM can improve the morphology of liver cell, reduce the degree of hepatic cord disorders and restore the cell morphology close to normal. The cause of OPUM prevents cholesterol gallstone formation maybe due to protect the integrity of the liver cells, lower CSI, and reduce cholesterol crystal formation and hence prevent cholesterol gallstone formation.
Animals ; Aspartate Aminotransferases ; blood ; Bile ; chemistry ; Cholesterol ; blood ; Gallbladder ; Gallstones ; metabolism ; prevention & control ; Liver ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred C57BL ; Piper ; chemistry ; Plant Oils ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Random Allocation ; Superoxide Dismutase ; metabolism ; Triglycerides ; blood

OBJECTIVETo find out potential molecular targets for gallbladder carcinoma diagnosis and treatment by analyzing and comparing the proteins expressed in human gallbladder carcinoma tissue and benign gallbladder tissue.

METHODSProteomic analysis of 6 human gallbladder carcinoma tissues and 6 benign gallbladder tissues was carried out. Total proteins of the carcinoma tissue and benign gallbladder tissue were separated by two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were analyzed and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Immunohistochemistry was used to examine the expression of PEBP1 protein in an independent series of samples.

RESULTSProtein extracts of individual samples in each type of tissues were separated on two-dimensional gels. There were forty six differentially expressed proteins in the gallbladder carcinom tissues. Seventeen proteins were successfully identified by MS, in which nine proteins were overexpressed in tumors while the other eight proteins were underexpressed. The increased level of PEBP1 protein in gallbladder carcinoma was further confirmed by immunohistochemical analysis.

CONCLUSIONSeventeen differentially expressed proteins were successfully characterized by comparative proteomic analysis. Those results may provide scientific foundation for screening the molecular biomarkers which can be used in diagnosis and treatment of gallbladder carcinoma, as well as to improve its prognosis and provide a new clue for carcinogenesis research of gallbladder carcinoma.

Adenocarcinoma ; diagnosis ; metabolism ; pathology ; Adult ; Aged ; Biomarkers, Tumor ; analysis ; Electrophoresis, Gel, Two-Dimensional ; Gallbladder Neoplasms ; diagnosis ; metabolism ; pathology ; Gallstones ; diagnosis ; metabolism ; pathology ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Middle Aged ; Phosphatidylethanolamine Binding Protein ; metabolism ; Proteomics ; methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization