Fibronectin expression is critical for liver fibrogenesis in vivo and in vitro.

Increased fibronectin (FN) expression has an important role during liver fibrosis. The present study examined FN expression in rats subjected to carbon tetrachloride (CCl4)­induced liver fibrosis. In addition, the potential mechanisms underlying fibrogenesis were investigated by exposing hepatic stellate cells (HSCs) to transforming growth factor­ß (TGF­ß), which is a known inducer of myofibroblastic transformation of HSCs. Briefly, a rat model of liver fibrosis was created by administering intraperitoneal injections of CCl4. Furthermore, HSC­T6 cells were stimulated with increasing doses of recombinant TGF­ß over 24 h. Hepatic fibrosis gradually increased following CCl4 administration in vivo. Western blotting and immunohistochemistry demonstrated that fibronectin (FN), TGF­ß and α­smooth muscle actin (SMA) expression was increased following CCl4 injection, and the maximum expression levels were observed at 8 weeks. Once CCl4 treatment had been terminated, the expression levels of FN, TGF­ß and α­SMA progressively declined to near baseline levels. Western blotting and quantitative polymerase chain reaction demonstrated that FN expression was gradually increased in response to TGF­ß­stimulation of HSCs; maximum expression was achieved 12 h post­treatment (P<0.01 vs. the baseline). In conclusion, these findings indicated that FN expression is an early and progressive event that occurs during liver fibrogenesis in vivo and in vitro.

Isolation of antifungal compound from Paeonia suffruticosa and its antifungal mechanism.

OBJECTIVE: To isolate antifungal compound from Paeonia suffruticosa, and to find the antifungal mechanisms by observing the ultrastructural modifications of yeasts in growth phase produced by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG). METHODS: Peony (Paeonia suffruticosa) root bark (PRB) was separated by solvent extraction and purified by high performance liquid chromatography (HPLC) method using analytical and preparative reversed phase C18 column on the basis of bio-assay method. In order to investigate the antifungal mechanism of PGG, Yeasts were submitted to different concentrations [3 × minimum inhibition concentration (MIC), 0.3 × MIC] for 1 h under constant stirring at 30 °C, and transmission electron microscopy was performed. RESULTS: Based on the antifungal activity of PRB on Candida glabrata CBS138, the antifungal compound were isolated in ethyl acetate layer of PRB and identified as PGG by mass spectrometry, 1H nuclear magnetic resonance (NMR) analyses, with molecular weight of 940 and molecular formular as C41H32O26. Transmission electron microscopy showed that PGG degraded the cell wall envelope. CONCLUSION: The results suggest that PGG may be responsible for the antifungal activity of PRB by disrupting the structure of cell wall directly.

Telmisartan attenuates hepatic fibrosis in bile duct-ligated rats.

AIM: To evaluate the antifibrotic effect of telmisartan, an angiotensin II receptor blocker, in bile duct-ligated rats. METHODS: Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats, model rats underwent common bile duct ligation (BDL), and BDL rats treated with telmisartan (8 mg/kg, po, for 4 weeks). The animals were sacrificed on d 29, and liver histology was examined, the Knodell and Ishak scores were assigned, and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining. The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot, respectively. RESULTS: The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35, P=0.015). However, there was no significant difference in inflammation between the two groups, both of which showed moderate inflammation. Histologically, treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis. Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS, and decreased the mRNA levels of ACE, angiotensin II type 1 receptor (AT1-R), collagen type III, and transforming growth factor ß1 (TGF-ß1). Moreover, treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins, and inhibited the expression levels of ACE and AT1-R protein. CONCLUSION: Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.