RESUMEN
This study aimed to examine changes in levels of cytokine and T cell surface molecules in chronic hepatitis B (CHB) patients receiving sequential interferon therapy following 1-year nucleos(t)ide analogs (NAs) treatment. Cytokine levels were measured in 30 patients, and T cell surface molecule expression was measured in 48 patients receiving sequential interferon therapy and 24 patients only receiving NA mono-therapy. An HBsAg titer of <0.05 IU/ml was defined as a "functional cure." In the cured group (HBsAg < 0.05 IU/ml), a decreasing probability was observed in IFN-γ (after Week 0), and IL-22 and IP-10 (after Week 12). In the non-cured group (HBsAg ≥ 0.05 IU/ml), a probability of slightly decreasing was observed for IFN-γ (after Week 12), and a probability of increasing IP-10 concentration (after Week 0) was observed. Generalized estimating equation (GEE) analyses showed significant differences in the levels of IL-10, IL-23, CCL-3, IL-1ß, IL-2, and IL-12P70 between the two groups. In GEE analysis, there were significant differences in expressions of CD45RO+ between the cured group and the non-cured group. The frequencies of T cells expressing Tim-3, CD62L, and CD152 were significantly lower in the sequential interferon therapy group than in the NA mono-therapy group. Changes in cytokine levels (IFN-γ, IP-10, IL-10, IL-23, CCL-3, IL-1ß, IL-2, and IL-12P70) and T cell surface molecules (CD45RO+ ) may predict HBsAg seroconversion in CHB patients receiving sequential interferon therapy. The period from Weeks 12 to 24 during sequential interferon therapy may be a critical time of immune status change.
Asunto(s)
Citocinas/sangre , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Linfocitos T/metabolismo , Adulto , Antivirales/uso terapéutico , Antígeno CTLA-4/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/inmunología , Humanos , Interferones/uso terapéutico , Selectina L/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Persona de Mediana Edad , Nucleósidos/uso terapéutico , Nucleótidos/uso terapéutico , Seroconversión/efectos de los fármacos , Resultado del TratamientoRESUMEN
Two-pore-domain (KCNK, K2P) K+ channels are transmembrane protein complexes that control the flow of ions across biofilms, which underlie many essential cellular functions. Because KCNK family members are known to contribute to tumorigenesis in various types of cancer, we hypothesized that they might be differentially expressed in hepatocellular carcinoma (HCC) cells as compared to healthy tissue and serve as diagnostic or prognostic biomarkers. We tested this hypothesis through bioinformatic analyses of publicly available data for the expression of various KCNK subunits in HCC. We observed reduced expression of KCNK2, KCNK15, and KCNK17 in liver cancer, as well as overexpression of KCNK9, all of which correlated with a better prognosis for HCC patients per survival analyses. Moreover, ROC curves indicated that KCNK2, KCNK9, KCNK15, and KCNK17 levels could be used as a diagnostic biomarker for HCC. Finally, our western blot and qRT-PCR results were consistent with those obtained from bioinformatic analyses. Taken together, these results suggest that KCNK2, KCNK9, KCNK15, and KCNK17 could serve as potential diagnostic and prognostic biomarkers of HCC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Canales de Potasio de Dominio Poro en Tándem/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
The association between serum hepatitis C virus (HCV) load and hepatic injury in HCV-infected patients has been extensively investigated. The present study aimed to investigate the association between HCV load in hepatic parenchyma cells and hepatic injury in HCV-infected patients. A total of 56 HCV-infected patients were included in the present retrospective study. The serum HCV mRNA was determined using quantitative polymerase chain reaction, while the hepatic parenchyma cell volume and HCV mRNA in hepatic parenchyma cells were also determined. Hepatic injury was evaluated on the basis of the severity of inflammation and fibrosis. The results demonstrated that there were evident differences in the mean serum HCV RNA levels and the HCV load/parenchyma cell volume among the various grades of hepatic inflammation (G1-G4) when groups with the least and most inflammation were compared (G1 vs. G4; P<0.05). Significant differences in the HCV load existed between groups divided according to the fibrosis grade; in addition, differences existed between fibrosis grades S1 and S2, and S2 and S4 when comparing serum HCV RNA levels (P<0.05). Similarly, differences existed between every two fibrosis stages (S0 vs. S4, S2 vs. S3, and S2 vs. S4; P<0.05) when viral loads and parenchyma cell volumes were compared (F=2.860, P<0.05). Furthermore, the fibrosis staging was correlated with the viral load/parenchyma cell volume (F=2.670, P<0.05). In conclusion, hepatic fibrosis grade was found to be associated with HCV load in parenchyma cells. The results of the present study demonstrated that the viral load in parenchyma cells is a more appropriate index compared with the serum viral load for evaluating HCV replication in hepatocytes, and may function as an important factor in HCV-infected hepatic injury evaluation.
RESUMEN
Previous studies have determined that activated hepatic stellate cells (aHSCs) promote the progression of hepatocellular carcinoma (HCC) by increasing angiogenesis in cancerous tissues. In addition, angiopoietin 1 (Ang1) has been reported to be involved in tumor growth and metastasis via the promotion of angiogenesis. It remains unclear whether aHSCs and Ang1 are involved in the angiogenesis in HCC. A total of 25 HCC and tumoradjacent tissues, and 21 normal liver tissues were used in the present study. Immunohistochemistry (IHC) was used to detect the expression of Ang1 and α smooth muscle actin (αSMA). The expression of CD34 was also analyzed using IHC to evaluate the microvessel density (MVD). The protein expression levels of Ang1 were evaluated using western blot analysis. The association between aHSC, Ang1 and angiogenesis was determined using Spearman's rank correlation coefficient. The present study determined that the expression of αSMA, Ang1 and MVD (CD34) was significantly higher in the HCC tissues when compared with tumoradjacent tissues and normal liver tissues. Spearman's rank analysis identified a positive correlation between the expression of αSMA, Ang1 and CD34. This suggests that αSMApositive aHSCs promoted angiogenesis by expressing Ang1, resulting in the proliferation and metastasis of HCC.
Asunto(s)
Angiopoyetina 1/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Transformación Celular Neoplásica/metabolismo , Células Estrelladas Hepáticas/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Actinas/metabolismo , Adulto , Anciano , Angiopoyetina 1/genética , Antígenos CD34/metabolismo , Biomarcadores de Tumor , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismoRESUMEN
AIM: To study the inhibitory effect of mononuclear bone marrow cell (BMC) transplantation on carbon tetrachloride (CCl(4)) -induced liver fibrosis in rats. METHODS: Rat liver fibrosis models were induced by CCl(4) and alcohol administration. After 8 wk, twenty rats were randomly allocated into treatment group (n = 10) and control group (n = 10). BMC were infused into the rats in treatment group via the portal vein, while heparinized saline was infused in control group. CCl(4) was hypodermically injected into the rats twice a week for 4 wk. At the end of wk 12, all rats were humanely sacrificed. Liver samples were taken and stained with HE or Masson trichrome. The general conditions, liver fibrosis (hydroxyproline and collagen fibre) and liver pathological grades in rats were evaluated. RESULTS: The general conditions of the rats in treatment group improved markedly, but not in control group. Hydroxyproline was 504.6 +/- 128.8 microg/g in treatment group, and 596.0 +/- 341.8 microg/g in control group. The percentage of collagen fibre was 3.75% +/- 0.98% in treatment group and 5.02% +/- 0.44% in control group. There was a significant difference between the two groups (P < 0.05). Liver pathological grade decreased from grade IV to grade III partially in treatment group (P < 0.05) with no obvious improvement in control group (P > 0.05). There was a significant difference between treatment group and control group (P < 0.05). CONCLUSION: Transplantation of BMC can improve liver fibrosis due to chronic liver injury in rats.