ABSTRACT
BACKGROUND: The heme oxygenase/carbon monoxide (HO/CO) system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin (COHb) level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis (HBC) complicated by hepatic encephalopathy (HE), and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC. METHODS: According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group (group N) consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome (HRS), upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis (SBP) in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades (I, II, III, and IV), PaO2, SaO2 and hypoxemia were analyzed. RESULTS: The COHb level in group P-H ((1.672 ± 0.761)%) was significantly higher than that in group N ((0.983 ± 0.231)%) (P < 0.01), and the level in group H ((2.102 ± 1.021)%) was significantly higher than groups P-H and N (P < 0.01). A positive correlation was observed between the COHb concentration and the grade of HE (r(s) = 0.357, P = 0.004). There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices ((2.302 ± 1.072)% vs. (1.802 ± 1.041)%, P > 0.05) or the occurrence of SBP ((2.960 ± 0.561)% vs. (2.030 ± 1.021)%, P > 0.05). Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS ((2.502 ± 1.073)% vs. (1.981 ± 1.020)%, P = 0.029). The COHb level had a negative correlation with PaO2 (r = -0.335, P = 0.007) while no statistically significant relationship was found with SaO2 (r = -0.071, P > 0.05). However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased ((2.621 ± 0.880)% vs. (1.910 ± 0.931)%, P = 0.011). CONCLUSIONS: COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.
Subject(s)
Carboxyhemoglobin/metabolism , Fibrosis/complications , Fibrosis/virology , Hepatic Encephalopathy/metabolism , Hepatitis B virus/pathogenicity , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
The Akt signaling pathway has been implicated in a wide range of cellular functions involving cell survival and proliferation, angiogenesis, metabolism and cell migration. Accumulating evidence suggests that Akt perturbations play an important role in human malignancy. Here, we investigated Akt perturbation in nickel-transformed cells. Chronic treatment of human bronchial epithelial BEAS-2B cells with low doses of nickel chloride resulted in cell transformation demonstrated by anchorage-independent (AI) growth, increased cell growth and alterations of cell growth pattern. Western blot assays show that phosphorylation of Akt at Ser473, but not that of p38, JNK and ERK, was increased in nickel-transformed cells compared with controls. Inhibition of Akt or PI3K by pharmacological or biochemical interference suppressed nickel AI growth and cell growth of transformed cells. Activation of Akt led to inhibition of GSK3ß by phosphorylation at Ser9 in nickel-transformed cells. In addition, two major anti-apoptotic proteins of the Bcl family, Bcl-2 and Bcl-XL, were increased in nickel-transformed cells. By employing the small interfering RNA technique (siRNA), our results showed that siRNA Akt attenuated the expression of Bcl-2 and Bcl-XL in nickel-transformed cells, indicating that induction of Bcl-2 and Bcl-XL was likely mediated through Akt. ROS generation was decreased in nickel-transformed cells compared with controls. Moreover, down-regulation of retinoblastoma protein (Rb) was observed in nickel-transformed cells. Taken together, these findings demonstrate that activation of Akt, followed by GSK3ß inhibition and Bcl-2, Bcl-XL up-regulation and decrease of ROS generation, along with a synergistic effect of Rb down-regulation may cause apoptosis resistance, contributing to the overall mechanism of nickel carcinogenesis.
Subject(s)
Carcinogens/pharmacology , Epithelial Cells/drug effects , Glycogen Synthase Kinase 3/metabolism , Nickel/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction , Cell Line, Transformed , Cell Transformation, Neoplastic/drug effects , Down-Regulation/drug effects , Enzyme Activation/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Glycogen Synthase Kinase 3 beta , Humans , Mitogen-Activated Protein Kinases/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Reactive Oxygen Species/metabolism , Retinoblastoma Protein/metabolism , Signal Transduction/drug effects , Tumor Suppressor Protein p53/metabolism , Up-Regulation/drug effectsABSTRACT
With the cloning of nuclear male fertility genes, learning of nuclear male fertility not only limited in genetic analysis and cell biology, but also advanced in molecular basis of male nuclear sterility and postulated in possible mechanisms of nuclear male sterility. The objectives of this paper are to review the related progress of plant nuclear male sterility.
