The Role of TGF-β_1 in Mice Hepatic Fibrosis by Schistosomiasis Japonica

lthasalreadybeenestab1ishedthatthehepaticfibrosisischaracterizedbyhyperplasiaandabnormaldepositofextrahepatocellularmatrix,especiallycolla-gen.Transforminggrowthfactor--5,(TGF--5,)isre-gardedasanimportantmodulationfactorinprocessofhepaticfibrosisformation.Tofurthere1ucidatetheroleofTGF--P,inhepaticfibrosisformationcausedbySchistosomiasisiaponl/a,weusedELISAandVGstainingtostudythechangeofthelevelofserumTGF--0,andlivercollagenfiberandreticularfiberinmlce.1MATERIALSANDMETHODS1.1Expe…     

The potential role of PDGF, IGF-1, TGF-β expression in idiopathic pulmonary fibrosis

Ｉｄｉｏｐａｔｈｉｃｐｕｌｍｏｎａｒｙｆｉｂｒｏｓｉｓ (ＩＰＦ) ,ａｌｓｏｒｅｆｅｒｒｅｄａｓｃｒｙｐｔｏｇｅｎｉｃｆｉｂｒｏｓｉｎｇａｌｖｅｏｌｉｔｉｓ ,ｉｓａｐｒｏｇｒｅｓｓｉｖｅｉｎｔｅｒｓｔｉｔｉａｌｌｕｎｇｄｉｓｅａｓｅｏｆｕｎｋｎｏｗｎｅｔｉｏｌｏｇｙ Ｃｏｎｖｅｎｔｉｏｎａｌｔｒｅａｔｍｅｎｔｗｉｔｈｃｏｒｔｉｃｏｓｔｅｒｏｉｄｓａｎｄｉｍｍｕｎｏｓｕｐｐｒｅｓｓｉｖｅｔｈｅｒａｐｙｈａｓｂｅｅｎｄｉｓａｐｐｏｉｎｔｉｎｇ 1　Ｉｎｆｉｌｔｒａｔｉｏｎｂｙｉｎｆｌａｍｍａｔｏｒｙｃｅｌ…     

The role of proteomics in hepatic metastasis in colorectal cancer

1Introduction Colorectalcancer(CRC)isoneofthemostcom monmalignanciesworldwide.Mostcolorectalcancer patientsdevelopmetastasistotheliverduringthe courseofthedisease.Oncelivermetastaseshavede veloped,thenaturalcourseofthediseaseisassociated withpoorprognosis,resultinginthedeathof36-81%ofpatients.Surgeryistheprimarytreatment optionforisolatedmetastases,butonly20%to25%ofpatientsdisplayinghepaticmetastasesaresuitable forresection,andpostoperationrecurrenceisfre quent.Thesuccessofmetastatichepaticc…     

Expression of conneetive tissue growth factor in sinusoidal endothelial cell of schistosomal hepatic fibrosis mice

Objective To explore the possible correlations of connective tissue growth factor （CTGF）, liver sinusoidal endothelial cell and the formation of basal membrane under hepatic sinusoidal endothelial cells by observing the expression of CTGF in sinusoidal endothelial cells of schistosomal hepatic fibrosis mice. Methods The liver fibrosis model was established by abdominal infection with schistosomal cercaria. Both model group and control group had 40 mice each.     

Colchicine reduces hepatic fibrosis in mice infected with Schistosoma japonicum.

OBJECTIVE Colchicine has been used clinically to treat hepatic cirrhosis caused by multiple etiologies.

METHODS The effect of colchicine on the liver fibrosis of mice infected with Schistosoma japonicum were studied. The morphological observation and morphometric analysis of the infected and untreated, and infected and treated groups were proceeded under the light microscopy, and morphological observation was made under electron microscopy.

RESULTS The results of morphometriic analysis in histological sections showed that the collagen fibers area per schistosome's egg was decreased in the infected and treated groups 10 to 13 weeks after infection. The decrease in the group of 13 weeks was significant statistically. The egg numerical density on area increased continuously from 10 to 13 weeks in both untreated and treated groups in similar degree. The ultrastructural study showed the accumulation of collagen fibrils around the hepatocytes and in the space of Disse decrease and ultrastructural lesion of hepatocytes get recovery in the treated group.

CONCLUSIONS These findings suggest that colchicine has therapeutic effect on schistosomal liver fibrosis, through not only killing off the schistosome but interfering the metabolism of collagen.

     

Effect of kangxianling on hepatic fibrosis in murine schistosomiasis

ＥｆｆｅｃｔｏｆｋａｎｇｘｉａｎｌｉｎｇｏｎｈｅｐａｔｉｃｆｉｂｒｏｓｉｓｉｎｍｕｒｉｎｅｓｃｈｉｓｔｏｓｏｍｉａｓｉｓＹａｎｇＹｕｎｇａｏ（杨运高）；ＧｕｏＺｈｅｎｇｑｉｕ（郭振球）；ＹｕａｎＺｈａｏｋａｉ（袁肇凯）；ＧｕｏＳｈｏｕｈｅｎｇ（郭绶衡...     

The role of Kupffer cells in the development of hepatic dysfunction during sepsis.

The effect of Kupffer cell blockade on hepatic function during sepsis was evaluated in this study. Methyl palmitate suspension 100 mg/100 g administered intravenously suppressed the phagocytic activity as the phagocytic index K decreased from 0.0493 +/- 0.0089 to 0.0150 +/- 0.0035 in rats. Sepsis was produced by the method of cecal ligation and needling perforation (CLP). At the end of 15 hours after CLP the hepatic adenosine triphosphate (ATP) level and ketone body ratio decreased significantly. But in rats pretreated with methyl palmitate 24 hours prior to CLP, the ATP level returned to the normal control level (1.6906 +/- 0.06-2.2323 +/- 0.13 mumol/g) and ketone body ratio remained at significantly higher values (0.26 to 0.68). After CLP, the liver lipoperoxide (LPO) concentration increased and glutathione (GSH) contents decreased significantly. When the septic rats were pretreated with methyl palmitate, both the LPO and GSH returned to the normal control level (62.69 +/- 1.7 to 44.62 +/- 2.12 and 159.85 +/- 9.7 to 222.27 +/- 11.34). It is concluded that the hepatic dysfunction is modulated at least to a greater extent by many of the toxic mediators released by the activated Kupffer cells during sepsis.

     

The Dynamic Change of TGF-β1 in the Myocardial Remodeling of Rat after Myocardial Infarction

Chronic heart failure is the leading cause of mortality and morbidity in most countries. Ventricular remodeling was the important pathophysiological process of heart failure. Mechanical overload, neurohormones and system nerve adrenal gland system can evoke remodeling. There are plentiful evidence indicating that inflammation plays an important role in the ischemic cardiac disease[1—3]. In this study we used the MI rat to observe the morpho- logical change of the ventricle, expression of the…     

The role and significance of enteral nutrition to the expression of TGF-β1 in the mucosa of the small intestine of rats with obstructive jaundice

目的 探讨肠内营养(EN)对梗阻性黄疸(OJ)大鼠肠黏膜上皮细胞凋亡及TGF-β1表达的影响及意义.方法 40只Wistar大鼠随机分为正常对照组、假手术组、OJ组、OJ+能全素组.OJ+能全素组给予肠内营养10 d,总能量提供为630 kJ/(kg·d),含氮量1.0 g/(kg·d).TUNEL法检测肠黏膜上皮细胞凋亡率,免疫组织化学法检测肠黏膜TGF-β1的表达.结果 OJ+能全素组肠黏膜细胞凋亡指数低于OJ组(P﹤0.05),OJ组大鼠肠黏膜TGF-β1阳性细胞表达显著减少(P＜0.01).OJ+能全素组大鼠肠黏膜TGF-β1阳性细胞表达与OJ组比较明显增加,差异显著(P＜0.01).结论 肠内营养可抑制肠黏膜上皮细胞凋亡,促进肠黏膜上皮细胞TGF-β1分泌,维持肠黏膜屏障的完整性,从而防止OJ时细菌和内毒素的移位.     

Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice

Background Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycininduced pulmonary fibrosis in mice. Methods Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days. We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis. Results Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen （Ⅰ and Ⅲ） mRNA expression induced by bleomycin. Moreover, simvastatin down-regulated the increased expression of transforming growth factor-β1 （TGF-β1） and connective tissue growth factor （CTGF） induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-a （TNF-α） in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore, the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration. Conclusions Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-β1 and CTGR These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.     

Non-invasive diagnostic screening of hepatic fibrosis in patients with chronic hepatitis B

Liver cirrhosis is usually associated with complications which can be effectively prevented. In the case of compensated cirrhosis, earlydiagnosis is essential. Liver biopsies are used as the primary method for the diagnosis of compensated cirrhosis. In clinical practice, the use of liver biopsies has several limitations including complications, which lead to a death rate of 0. 015%, discomfort, and longer hospitalization. These limitations prevent the use of liver biopsies as a general screening     

Upregulation of TNF-α mRNA in hepatic fibrosis rats induced by dimethylnitrosamine

Objective：To observe the expression level of TNF-α mRNA in rats with hepatic fibrosis induced by dimethylnitrosamine （DMN） and to explore its relationship with collagen metabolism and its diagnostic value for hepatic fibrosis.Methods： Twenty-five male Wistar rats were randomly divided into normal control group （n=10） and model group （n=15）. Model rats were induced by DMN for 4 weeks and at final stage were executed. TNF-α mRNA were detected by RT-PCR and the inflammatory necrosis and collagen deposition in hepatic tissue were observed by HE stain and Sirius red stain. The liver functions were determined by automatic biochemical analytic device. The serum marks of liver fibrosis, such as HA, LN and Ⅳ-C were measured with ELISA and RIA. Results： In this study, the rat model of liver fibrosis induced by DMN was successfully constructed. RT-PCR reveals that TNF-α mRNA expression in control group is lower than that of model group. The liver functions of model group were impaired compared with those of the control group （P〈0.01）. Semi-quantitive analysis revealed that TNF-α/β-actin of normal rats was 0.39±0.12, while 0.93±0.05 of model rats. The concentration of HA （434.44±98.81 vs 252.9±26.59 ng/ml, P〈0.01）, LN （70.67±6.32 vs 37.90±5.97 ng/ml, P〈0.01） and Ⅳ-C （79.39±10.52 vs 21.40±4.17 ng/ml, P〈0.01） were significantly increased in the model group as well. Changes of the indexes were similar to the pathological damage of the liver. Conclusion： The results suggested that activation of TNF-α in liver tissues may be the common pathogenic mechanism of liver fibrosis. TNF-α may be a useful index for the diagnosis of hepatic fibrosis which worthies further investigation.     

Implication of EMT Induced by TGF-β1 in Pancreatic Cancer

This study examined the implication of EMT induced by TGF-β1 in pancreatic cancer invasion. TGF-β1 expression was determined in 29 cases of human pancreatic carcinoma （PC） by immunohistochemistry and the results were compared with those of pathological examination. Moreover, the effects of TGF-β1 on the phenotype and invasion of pancreatic cancer cell line Panc-1 were also investigated. TGF-β1 was detected in 12 cases （41.4 %） of PC. Significant correlation was found between the expression of TGF-β1 and lymph node involvement （P=0.047） and the depth of invasion （P=0.035）. TGF-β1 obviously promoted EMT of Panc-1 cell lines and their invasion ability was substantially enhanced. TGF-β1 may promote the malignancy of pancreatic cancer by triggering EMT.     

Characteristics of mRNA levels of hepatic key enzymes in cholesterol metabolism of genetically gallstone-susceptible mice

Our previous study indicated that biliary cholesterol hypersecretion was the key pathophysiological defect of gallstone formation. Lith genes determine biliary cholesterol hypersecretion and susceptibility to cholesterol gallstone formation in C57L mice. In order to explore the molecular mechanism of biliary cholesterol hypersecretion, the present study measured and analysed mRNA levels of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase ( HMG-CoA R ), acyl-CoA, cholesterol acyltransferase ( ACAT ), cholesterol 7α-hydroxylase (C7H) and low-density lipoprotein receptor (LDLR) in genetically gallstone-susceptible C57L and gallstoneresistant AKR mice.     

The role of Fas-FasL in insulitis in nonobese diabetic mouse

Type 1diabetesresultsfromautoimmunedamagetoβcellsandinsulitistypicallycharacterizesitspathologicalpresentation Apoptosiscouldbeamainmechanism ThereareseveralpathwaysofapoptosisincludingFas FasL 1　Fasisatype 1transmembraneglycoproteininthesuperfamilyofTNF/NGFreceptorsandFasL (thespecificligandforFasinvivo)isatype 2transmembraneglycoproteininthesuperfamilyofTNF 2 Theirinteractionforinducingapoptosisisimportantinmanyprocesses 3　Theirmalfunctioncanleadtotheover proliferationoftheautoreac…