RESUMO
BACKGROUND: In China, hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is the most common liver failure characterized by serious clinical syndromes of liver decompensation with a very high mortality. Bacterial and/or fungal infections are the most common complications that are associated with high short-term mortality. Bacterial translocation from the intestine, impaired hepatic clearance, and immune paralysis of circulating immune cells are thought to contribute to infectious complications in liver failure. The control of bacterial and fungal infections is the key to improving HBV-ACLF outcomes. Active prevention, early diagnosis, and timely treatment of bacterial and fungal infections are essential for treating HBV-ACLF. AIM: To investigate the frequency and role of bacterial and fungal infections in patients with HBV-ACLF. METHODS: Patients with HBV-ACLF hospitalized at Taihe Hospital, Hubei University of Medicine from January 2014 to December 2017 were retrospectively enrolled. Patient-related information was retrieved from the hospital case database, including general information, blood biochemistry, complications, etc. According to the occurrence of secondary infection or not, the patients were divided into an infection group and a non-infection group. The sites, types, and incidences of bacterial and fungal infections and the influence of infections on the prognosis of HBV-ACLF were statistically analyzed. The risk factors for infections were assessed by unconditional logistic regression. RESULTS: There were 174 cases of HBV-ACLF that met the enrollment criteria, of which 114 (65.52%) were diagnosed with infectious complications. Infections occurred in the abdominal cavity (87 cases), respiratory tract (51 cases), urinary tract (18 cases), and biliary tract (10 cases). Patients with infectious complications had a significantly higher 28-d mortality (70.18%, 80/114) than those without (40.00%, 24/60) (70.18% vs 40.00%, P < 0.05). And patients with infectious complications had a much higher incidence of non-infectious complications (54.39%, 62/114) (54.39% vs 15.00%, P < 0.05), leading to an extremely high 28-d mortality of 88.71% (55/62) (P < 0.05). The grade of liver failure, period of hospital stay ≥ 30 d, age ≥ 45 years, and percentage of neutrophils > 70% were identified as risk factors for infectious complications. CONCLUSION: The high incidence of infectious complications in patients with HBV-ACLF is associated with severity and deterioration of the disease and may contribute to the extremely high mortality of these patients.
RESUMO
OBJECTIVE: To investigate the impact of Bmi-1-mediated NF-κB pathway on the biological characteristics of CD133+ liver cancer stem cells (LCSCs). METHODS: Flow cytometry was used to isolate CD133+ LCSC cells from Huh7, Hep3B, SK-hep1, and PLC/PRF-5 cells. CD133+ Huh7 cells were divided into Control, Blank, Bmi-1 siRNA, JSH-23 (NF-κB pathway inhibitor), and Bmi-1 + JSH-23 groups. The properties of CD133+ Huh7 cells were detected by the colony-formation and sphere-forming assays. Besides, Transwell assay was applied for the measurement of cell invasion and migration, immunofluorescence staining for the detection of NF-κB p65 nuclear translocation, and qRT-PCR and Western blotting for the determination of SOX2, NANOG, OCT4, Bmi-1, and NF-κB p65 expression. RESULTS: CD133+ Huh-7 cells were chosen as the experiment subjects after flow cytometry. Compared with CD133- Huh-7 cells, the expression of CD133, OCT4, SOX2, NANOG, Bmi-1, and NF-κB p65, the nuclear translocation of NF-κB p65, the number of cell colonies and Sphere formation, as well as the abilities of invasion and migration were observed to be increased in CD133+ Huh-7 cells, which was inhibited after treated with Bmi-1 siRNA or JSH-23, meanwhile, the cell cycle was arrested at the G0/G1 and S phases with apparently enhanced cell apoptosis. Importantly, no significant differences in the biological characteristics of CD133 + Huh-7 cells were found between the Blank group and Bmi-1 + JSH-23 group. CONCLUSION: Down-regulating Bmi-1 may inhibit the biological properties of CD133+ LCSC by blocking NF-κB signaling pathway, which lays a scientific foundation for the clinical treatment of liver cancer.
Assuntos
Antígeno AC133/metabolismo , Neoplasias Hepáticas/metabolismo , NF-kappa B/metabolismo , Células-Tronco Neoplásicas/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Transdução de Sinais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Imunofluorescência , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , NF-kappa B/genética , Complexo Repressor Polycomb 1/genéticaRESUMO
PURPOSE: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. MATERIALS AND METHODS: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. RESULTS: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory (TNF-α, IL-1ß, IL-6) and profibrogenic cytokines (TGF-ß1, COL1A1, α-SMA) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. CONCLUSION: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.