SUMMARY BackgroundA virological response to pegylated-interferon and ribavirin is typically associated with a prompt fall in serum transaminases. For some patients, transaminases rise during treatment.

The use of amphotericin B, liposomal or non-liposomal preparations at low doses, for prophylaxis of IFI in high-risk LT patients, is associated with a low incidence of serious fungal infection. In this randomised study, low-dose amBisome prophylaxis was associated with an increased likelihood of successful discharge from the ICU.

Preeclampsia (PE) is a pathological condition that manifests during pregnancy as the occurrence of an abnormal urine protein level and increased blood pressure due to inadequate cytotrophoblast invasion. To elucidate the mechanism underlying PE, the present study primarily focused on the regulatory effects and mechanism of the G protein γ 7 (GNG7) on placental cytotrophoblasts in a rat PE model. Initially, the PE model was established with 45 specific pathogen-free Sprague-Dawley rats (30 females and 15 males). The expression patterns of GNG7, 4E-binding protein 1 (4E-BP1), phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) and mammalian target of rapamycin (mTOR) were examined in the PE rats. Placental cytotrophoblasts isolated from normal and PE rats were treated with a small interfering RNA against GNG7, mTOR signaling pathway activator (HIV-1 Tat) or inhibitor (rapamycin). Following treatment, cell proliferation, differentiation and apoptosis were evaluated, and mTOR signaling pathway-related factors (4E-BP1, p70S6K and mTOR), cell proliferation-related factors (vascular endothelial growth factor and transforming growth factor-β1), differentiation-related factors [activator protein-2 (AP-2)α and AP-2γ], and apoptosis-related factors [B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein] were determined. Finally, soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) levels were measured via enzyme-linked immunosorbent assay. Initially, the mTOR signaling pathway was inactivated in the placental tissues and cytotrophoblasts in the PE rats. Silencing GNG7 reduced the levels of sFlt-1 and sEng and activated the mTOR signaling pathway. Silencing of GNG7 or activation of the mTOR signaling pathway enhanced cell proliferation and differentiation, but inhibited the apoptosis of placental cytotrophoblasts in the PE rats. Taken together, the results showed that GNG7 silencing repressed apoptosis and enhanced the proliferation and differentiation of placental cytotrophoblasts in PE rats through activation of the mTOR signaling pathway.

c-Fos/activator protein-1; human myometrial smooth muscle cells; onset of labor PREMATURE AND POSTTERM BIRTHS are major causes of neonatal morbidity and mortality. However, the onset of labor in humans is a complicated process that has not been fully clarified. Understanding the complex physiological process and the mechanism of the onset of labor may provide novel therapeutic strategies to prevent and treat premature delivery or postterm pregnancy.Corticotropin-releasing hormone (CRH), a 41-amino acid peptide, has been demonstrated to play an important role in uterine contraction and onset of labor (9, 12). In the nonpregnant state, CRH is mainly released by the hypothalamus and remains at a low level. During pregnancy, the placenta also synthesizes CRH and gradually becomes the major source of CRH in the human body (5). CRH concentration in peripheral blood is very low in the first trimester of pregnancy. Because of the large amount of CRH synthesized by the placenta beginning in the second trimester of pregnancy, plasma CRH increases exponentially with time (weeks) of gestation. Then it increases significantly and reaches its peak (585 pmol/l) at the onset of labor. CRH falls to its normal level (0.2-2 pmol/l) 24 h after delivery (19). Therefore, CRH is generally considered a promoter of labor (9, 12), but the labor-promoting mechanism of CRH remains unclear.The increased expression of connexin 43 (Cx43) in uterine muscle is an important factor in uterine contraction and onset of labor (10, 15). In the nonpregnant state and the first trimester of pregnancy, Cx43 expression in the myometrium is minimal. However, Cx43 mRNA and protein levels increase dramatically before labor (18). The nuclear transcription factor activator protein (AP)-1 can combine with many genes and, subsequently, regulate transcription of these target genes. There are AP-1 sites in the Cx43 gene promoter region. AP-1 facilitation of the transcription and expression of Cx43 in myometrial cells has been documented by Wu et al. (28) and Mitchell and Lye (14). Mitchell and Lye proved that c-Fos, the AP-1 subunit, plays an important regulatory function in Cx43 expression. Becquet et al. (3) and Autelitano and Cohen (2) found that CRH could facilitate AP-1 and upregulate expression of its subunit c-Fos in AtT-20 cells. However, no information about the association between the level of CRH and the change in c-Fos/AP-1 in myometrial tissues is available in the literature. Moreover, the mutual regulation among CRH, Cx43, and the AP-1 subunit c-Fos in the mechanism of labor onset remains unclear.We hypothesize that CRH may influence Cx43 expression in human myometrial smooth muscle cells (SMCs) through AP-1 and, thus, initiate labor. To investigate the regulatory effects of CRH on Cx43 expression in human myometrial cells and its potential activation of the c-Fos/AP-1 pathway, we employed primary cultured myometrial SMCs and a specific block of AP-1 sites.