Pregnancy and fetal outcomes of chronic hepatitis C mothers with viremia in China.

BACKGROUND: Data that assess maternal and infant outcomes in hepatitis C virus (HCV)-infected mothers are limited. AIM: To investigate the frequency of complications and the associated risk factors. METHODS: We performed a cohort study to compare pregnancy and fetal outcomes of HCV-viremic mothers with those of healthy mothers. Risk factors were analyzed with logistic regression. RESULTS: Among 112 consecutive HCV antibody-positive mothers screened, we enrolled 79 viremic mothers. We randomly selected 115 healthy mothers from the birth registry as the control. Compared to healthy mothers, HCV mothers had a significantly higher frequency of anemia [2.6% (3/115) vs 19.0% (15/79), P < 0.001] during pregnancy, medical conditions that required caesarian section [27.8% (32/115) vs 48.1% (38/79), P = 0.004], and nuchal cords [9.6% (11/115) vs 34.2% (27/79), P < 0.001]. In addition, the mean neonatal weight in the HCV group was significantly lower (3278.3 ± 462.0 vs 3105.1 ± 459.4 gms; P = 0.006), and the mean head circumference was smaller (33.3 ± 0.6 vs 33.1 ± 0.7 cm; P = 0.03). In a multivariate model, HCV-infected mothers were more likely to suffer anemia [adjusted odds ratio (OR): 18.1, 95% confidence interval (CI): 4.3-76.6], require caesarian sections (adjusted OR: 2.6, 95%CI: 1.4-4.9), and have nuchal cords (adjusted OR: 5.6, 95%CI: 2.4-13.0). Their neonates were also more likely to have smaller head circumferences (adjusted OR: 2.1, 95%CI: 1.1-4.3) and lower birth weights than the average (≤ 3250 gms) with an adjusted OR of 2.2 (95%CI: 1.2-4.0). The vertical transmission rate was 1% in HCV-infected mothers. CONCLUSION: Maternal HCV infections may associate with pregnancy and obstetric complications. We demonstrated a previously unreported association between maternal HCV viremia and a smaller neonatal head circumference, suggesting fetal growth restriction.

Upregulation of microRNA-351 exerts protective effects during sepsis by ameliorating skeletal muscle wasting through the Tead-4-mediated blockade of the Hippo signaling pathway.

Sepsis-induced skeletal muscle wasting may lead to various severe clinical consequences. Understanding molecular mechanisms of the regulation of the loss of skeletal muscle mass in septic patients remains a significant clinical challenge. The current study was conducted to establish septic mice models to explore the relationship between microRNA (miR)-351 and the transcription element apical (TEA) domain transcription factor (Tead)-4 gene and to investigate its effects on the skeletal muscle through mediating the Hippo signaling pathway in mice with acute sepsis. A total of 60 mice were collected to establish mouse models of acute sepsis. The positive expression rate of Tead-4 and the apoptotic index (AI) were measured. A dual-luciferase reporter gene assay was conducted to verify the targeting relationship between miR-351 and Tead-4. Furthermore, the muscle fiber diameter (MFD) and area (MFA) and the content of 3-methylhistidine (3-MH) and tyrosine (Tyr) were assessed. The expression levels of miR-351, p38-MAPK, Yes-associated protein, Tead-4, B-cell lymphoma X protein (Bax), and Caspase-3 were determined with quantitative RT-PCR and Western blot analysis. Finally, cell viability, apoptosis, and levels of inflammatory factors, including IL-1ß, IL-6, IGF-1, TNF-α, and monocyte chemoattractant protein-1 were detected by 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and ELISA. Initially, Tead-4 protein expression was higher in skeletal muscle tissues of mice with acute sepsis. Tead-4 was identified to negatively regulate miR-351. Upregulation of miR-351 increased MFA and MFD, muscle weight water content, Bcl-2 expression levels, and cell viability. Up-regulation of miR-351 reduced AI; 3-MH and Tyr content; positive expression of Tead-4 protein; the expression levels of p38-MAPK, Yap, Tead-4, Bax, and Caspase-3; apoptosis; and inflammatory responses. The current study demonstrated that up-regulation of miR-351 inhibits the degradation of skeletal muscle protein and the atrophy of skeletal muscle in mice with acute sepsis by targeting Tead-4 through suppression of the Hippo signaling pathway. Thus, miR-351 overexpression may be a future therapeutic strategy for acute sepsis.-Zhang, L.-N., Tian, H., Zhou, X.-L., Tian, S.-C., Zhang, X.-H., Wu, T.-J. Upregulation of microRNA-351 exerts protective effects during sepsis by ameliorating skeletal muscle wasting through the Tead-4-mediated blockade of the Hippo signaling pathway.

Expression of discoidin domain receptors (DDR2) in alcoholic liver fibrosis in rats.

BACKGROUND AND AIMS: We undertook this study to evaluate the expression of discoidin domain receptor 2 (DDR2) and its relationship with alcoholic liver fibrosis. METHODS: Liver fibrosis was induced by intragastric administration of alcohol in 30 rats. Pathological changes and ultrastructure of the liver were studied. The expression of DDR2 mRNA and protein was detected by RT-PCR and Western blot, respectively, at weeks 12, 16 and 20 during the alcohol administration. RESULTS: In the control group (con) (n = 10), DDR2 mRNA expression and DDR2 protein were 1.02 ± 0.13 (con ratio x10⁻³) and 0.32 ± 0.03, respectively. In the study groups there was a progressive increase in DDR2 mRNA expression from weeks 12, 16 and 20 (3.64 ± 1.69, 8.34 ± 2.39, 15.73 ± 4.57 con ratio x10⁻³, p <0.05). There was also a progressive increase in DDR2 protein from weeks 12-20 (0.48 ± 0.05, 0.74 ± 0.06 and 0.99 ± 0.05, p <0.05). The mean DDR2 mRNA and protein in the three study groups was higher than in the control group (p <0.01). The expressions of DDR2 mRNA and protein were positively correlated with collagen type I, III and IV in liver tissues as well as with the serum biomarkers of liver fibrosis, collagen type III, hyaluronic acid, collagen type IV and laminin (p <0.01). CONCLUSIONS: The expression of DDR2 in this alcohol-induced liver fibrosis rat model is enhanced. The expression of DDR2 is closely associated with collagens in the fibrotic liver tissues.

[An experimental study on the relationship between proteasome LMP7 subunit and alcoholic liver disease].

OBJECTIVES: To investigate the relationships between proteasome active center LMP7 subunit and the occurrence and development of alcoholic liver disease. METHODS: Eighty male Wistar rats, 170 to 190 g, were randomly divided into two groups: a model group (60 rats) and a control group (20 rats). The model group was given alcoholic intragastric administration plus an olive oil diet. Gavage, twice a day, was used to administer ethanol (30%) in a dose of 4 g/kg/d to the model group rats in the first 4 weeks. In the next 4 weeks, 40% ethanol in a dose of 5 g/kg/d was used, and then in the last 4 weeks, 50% ethanol in a dose of 6 g/kg/d was used. After infusion for 12 weeks, 15 rats (fatty liver group) were sacrificed. Others were divided into two groups; one was the hepatitis group with continued alcohol intragastric administration, the other was the hepatitis control group, receiving equal amounts of normal saline. Both groups were sacrificed after 4 weeks. By HE staining, histological pathology of the rat livers was analyzed. The expression of proteasome LMP7 subunit mRNA was examined by reverse transcription and real-time PCR. The content of LMP7 subunit protein was determined by Western blot. RESULTS: The LMP7 mRNA level of the fatty liver group was 36% of the control group. The level of the hepatitis control group was 51% of the control group. The level of the hepatitis group was the lowest, which was only 26% of the control group. Western blot results showed that the level of the LMP7 protein content of the control group was 0.50+/-0.01; the level was 0.39+/-0.02 of the fatty liver group; 0.30+/-0.04 of the hepatitis group, and 0.38+/-0.02 of the hepatitis control group. The differences of the LMP7 protein content and mRNA expression correlated with the severity of the pathological alterations of the livers. CONCLUSIONS: The proteasome LMP7 mRNA expression and protein content decreased in the alcoholic liver group. It may be one of the factors responsible for the decreased activity of proteasome and may play an important role in the pathogenesis of alcoholic liver disease.

[Expression of discoidin domain receptor 2 in different phases of alcoholic liver fibrosis in a rat model].

OBJECTIVE: To observe the expressions of discoidin domain receptor 2 (DDR2) in different phases of alcoholic liver fibrosis (ALF) in a rat model and to study the possible association between DDR2 and collagen deposition in ALF. METHODS: After an ALF rat model was established by alcohol gastrogavage and an olive oil diet, the liver histopathology was observed in different phases of the development of fibrosis. The expressions of DDR2 mRNA and protein were also detected by RT-PCR and Western blot respectively to make a dependability analysis with the index of ALF. RESULTS: (1) The expressions of DDR2 mRNA and protein increased gradually along with ALF aggravation. In the normal control group, they were respectively 1.023+/-0.132 and 0.321+/-0.027; in the model 1 group (week 12) they were 3.644+/-1.686, 0.476+/-0.046; in the model 2 group (week 16) they were 8.337+/-2.387, 0.738+/-0.057; and in the model 3 group (week 20) they were 15.730+/-4.569, 0.997+/-0.049. The differences of DDR2 mRNA (F = 21.74, P less than 0.01) and protein (F = 10.38, P less than 0.01) among these four groups were significant. (2) The expressions of DDR2 had a positive correlation with collagen type I, III, IV contents and the serum index of ALF, especially with type III and IV collagen and serum hexadecenoic acid. CONCLUSION: The expression of DDR2 in this ALF model correlates closely with collagen deposition in the liver, suggesting that it may play an important role in ALF pathogenesis.