Effects of bone morphogenetic protein-7 therapy on E3 ubiquitin ligase expression in mouse liver with experimentally induced fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>This study explored the dynamic expression of the E3 ubiquitin-protein ligase gene, Arkadia, in response to carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model and investigated the differential expression that occurs following treatment with the anti-fibrotic bone morphogenetic protein-7 (BMP-7).</p><p><b>METHODS</b>Thirty healthy male imprinting control region (ICR) mice were randomly assigned to three groups: normal (control; n = 6), CCl4-induced model group (model; n = 18), and CCl4-induced model with BMP-7 treatment group (treatment; n = 6). The model group was further divided into three subgroups (n = 6 each) for analysis at 4, 8 and 12 weeks after fibrosis induction. Liver fibrosis was induced by hypodermic injections of 60% CCl4 /peanut oil (5 mL/kg) to the hind legs of mice two-times per week in alternating legs for a period of 12 weeks. At week 9, the treatment group of CCl4-induced mice were given an intraperitoneal injection of BMP-7 (300 pg/g) simultaneously with that day's hypodermic injection of 60% CCl4 /peanut oil, and then every other day for a period of four weeks. The pathological changes in liver tissues were observed after staining with hematoxylin-eosin (HE) and Masson's trichrome. Messenger RNA (mRNA) and protein expression of Arkadia in liver were evaluated using reverse transcription-polymerase chain reaction and immunohistochemistry and Western blotting, respectively.</p><p><b>RESULTS</b>Mouse models of liver fibrosis were successfully established by CCl4 exposure. Arkadia, Smad7 and TGF-beta1 mRNA levels were up-regulated in the model group in a time-dependent manner (vs. control group), and BMP-7 treatment led to significant down-regulation of the CCl4-induced expression of the three genes (vs. control group: F = 812.80, 451.46, and 998.96, respectively; P less than 0.01). At week 12, the mRNA levels of Arkadia, Smad7, and TGF-b1 were significantly lower in the BMP-7 treatment group than in the model group (t = 12.108, 18.737, and 16.364, respectively; P less than 0.01). Arkadia, Smad7, and TGF-b1 protein staining was weak in the portal area of control liver tissue. In contrast, the model group showed significantly stronger staining for all three proteins in the portal area and in the cytoplasm of liver cells. The staining of Arkadia, Smad7, and TGF-b1 proteins was significantly lower in the treatment group (vs. control group: F = 8.399, 609.690, and 900.561, respectively; P < 0.01). At week 12, the protein levels of Arkadia, Smad7, and TGF-b1 were significantly lower in the treatment group than in the model group (t = 23.438, 11.667, and 42.889, respectively; P < 0.01).</p><p><b>CONCLUSION</b>Arkadia expression gradually increased along with the development of liver fibrosis but was suppressed by treatment with the anti-fibrotic factor, BMP-7.</p>

Dynamic expression of tropomyosin 1 in rat model of hepatic fibrosis and hepatic stellate cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic expression of TPM1 in rat model of hepatic fibrosis and hepatic stellate cells induced by TGFβ1.</p><p><b>METHOD</b>Thirty male SD rats were divided into control group (n = 6) and model group (n = 24). The rat model of hepatic fibrosis was established by intraperitoneal injection of dimethylnitrosamine(DMN). The sera were collected from portal vein and liver tissues were taken from animals 2, 4, 6, 8 weeks HSC-T6 cells were cultured and induced 48 hours by 5 ng/ml TGF-β1. The pathological changes of liver were observed by Hematoxylin-Eosin and Masson Staining. Reverse Transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and Western-blotting were used to determine the mRNA and protein expressions of TPM1, TGFβ1 and α-SMA in rat models and HSC-T6 cells and the localization of TPM1 in rat models.</p><p><b>RESULTS</b>Rat models of hepatic fibrosis were successfully established. TPM1 was lowly stained in the wall of blood vessels in portal areas in normal livers, in fibrotic livers TPM1 was mainly stained along the fibrotic septum. The mRNA and protein expressions of TPM1 and α-SMA in rat models of hepatic fibrosis increased at the week 2 and peaked at week 6, which was statistical significance compared to control group, P < 0.05; TGF-β1 increased at week 2 and it was higher than the levels in other groups at week 4, which was statistical significance compared to control group P < 0.05; Correlation analysis showed that TPM1 positively correlated with α-SMA and TGF-β1, rs = 0.688, rs = 0.692, P < 0.01. In HSC-T6, the mRNA expressions of TPM1 and α-SMA increased after being induced by TGF -beta1. compare with control group, the differences were significant, P less than 0.05.</p><p><b>CONCLUSION</b>TPM1 may be playing an important role in the occurrence and development of liver fibrosis. Maybe it could become a potential therapeutic target for hepatic fibrosis.</p>

Diagnosis of infective endocarditis by Duke criteria and a new national criteria in a cohort of 205 patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the value of the new national criteria (2 major or one major plus 3 minor criteria) with the Duke criteria for diagnosis of infective endocarditis (IE).</p><p><b>METHODS</b>A total of 205 patients with clinical diagnosis of IE admitted at West China Hospital of Sichuan University were included in this study. Among them, IE was pathologically confirmed in 97 patients. The sensitivities of both criteria for the diagnosis of IE were compared.</p><p><b>RESULTS</b>In 205 cases, the same microorganisms were detected twice in blood cultures in 13 cases (8.3%). Vegetations were detected by echocardiography in 183 patients (89.3%). In 97 cases with pathologically confirmed IE, the same microorganisms were detected twice in blood cultures in 6 cases (6.2%). Vegetations were detected by echocardiography in 89 patients (91.8%). IE diagnose was made in 44 (45.5%) and 86 (88.7%, P < 0.05 vs. Duke criteria) out of 97 pathologically confirmed IE patients by the Duke criteria and new national criteria, respectively. The specificities were 100% and 95.7% by Duke and new national criteria, respectively (P > 0.05).</p><p><b>CONCLUSION</b>With the addition of echocardiographic evidence of endocardial involvement and 2 minor criteria as definite diagnostic criteria, the sensitivity of the new national criteria is superior to that of the Duke criteria for diagnosing IE and the specificity for the diagnosis of IE between the two criteria is similar.</p>