The effect of highly active antiretroviral therapy on liver function in human immunodeficiency virus-infected pediatric patients with or without hepatitis virus co-infection.

BACKGROUND: Co-infection of hepatitis virus is common in human immunodeficiency virus (HIV) infected adults in China. But little is known about hepatitis virus co-infection in pediatric HIV-infected subjects. The study aimed to investigate the impact of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection and highly active antiretroviral therapy (HAART) on liver function of pediatric HIV-infected subjects. MATERIALS AND METHODS: A cohort study including 101 pediatric HIV-infected subjects with HBV/HCV co-infection and 44 pediatric comparators with HIV mono-infection was carried out in Henan Province of China from September 2011 to September 2012. All patients received HAART for 1-year. HBV and HCV infection was determined by antibody tests. HIV RNA load, CD4(+) T-cell counts and liver function were determined before and after HAART. The Student's t-test or a one-way ANOVA was used for normally distributed values and A Mann-Whitney U-test was performed for values without normal distribution using SPSS statistical package 18.0 (SPSS Inc.). RESULTS: After HAART for 1-year, the median levels of viral load were decreased to lower limit of detection in 90.34% pediatric HIV-infected subjects with/without HBV/HCV co-infection (P < 0.001), and CD4(+) T-cell counts increased significantly (P < 0.001). Compared with the pre-HAART, mean level of alanine aminotransferase (ALT) in each group had a significant increase after HAART (P < 0.01). The mean levels of ALT and aspartate aminotransferase (AST) in nevirapine (NVP) based HAART group increased significantly after HAART (P < 0.01). Mean change values of ALT and AST were significantly higher in the NVP based regimen group than in the efavirenz (EFV) based regimen group (P < 0.01). For HIV/HBV/HCV co-infected patients, mean change values of ALT and AST in NVP-based HAART group was significantly higher than that in EFV-based HAART group (P < 0.01). CONCLUSION: Highly active antiretroviral therapy can damage liver function in pediatric HIV-infected subjects, especially in those with HBV/HCV co-infection. NVP was more harmful to liver function of pediatric HIV-infected subjects than EFV.

Soluble CD14 Subtype in Peripheral Blood is a Biomarker for Early Diagnosis of Sepsis.

OBJECTIVE: To study the value of serum soluble CD14 subtype (sCD14-ST) in early diagnosis of sepsis. METHODS: Seventy-two patients were diagnosed with systemic inflammatory response syndrome, sepsis, or septic shock. Peripheral blood was collected at 0, 12, 24, and 48 hours after admission to the hospital. Levels of sCD14-ST, procalcitonin (PCT), hypersensitive C-reactive protein (CRP), and white blood cells (WBC) were determined. RESULTS: Levels of sCD14-ST in the patients with septic shock were higher than those in the other patients (P < .01) and peaked at 48 h. PCT and CRP levels were similar in the patients at admission but increased by 5 times to 10 times in the next 48 h, especially in the patients with septic shock. WBC levels remained high and did not change dramatically. Receiver operating characteristic analysis revealed that the area under the curve, sensitivity, and specificity values of sCD14-ST to diagnose sepsis were much higher than those of the other markers. CONCLUSION: Compared with PCT, CRP, and WBC, sCD14-ST is a better biomarker for the early diagnosis of sepsis.

Increased Levels of miR-155 are Related to Higher T-Cell Activation in the Peripheral Blood of Patients with Chronic Hepatitis B.

OBJECTIVES: MicroRNA-155 (miR-155) is an important regulator of immune responses in humans. However, its role in T-cell activation in hepatitis B virus (HBV) infection remains unclear. MATERIALS AND METHODS: Eighty-one patients with chronic hepatitis B (CHB), 77 HBV carriers, and 51 healthy controls were recruited. HBV DNA and serologic tests were carried out for each subject. Levels of miR-155 in peripheral blood were detected by quantitative reverse transcription/polymerase chain reaction. Immune activation of T-cells was determined by detection of surface molecules CD38 and HLA-DR using flow cytometry. RESULTS: We found higher miR-155 levels in CD4+ and CD8+ T-cells of CHB patients than HBV carriers or healthy controls (p < 0.01), moreover, miR-155 levels in the CD8+ T-cells of HBV carriers were higher than in healthy controls (p < 0.01). Furthermore, immune activation of CD4+ and CD8+ T-cells in CHB patients was much higher than in healthy controls (p < 0.01). CONCLUSION: Our findings suggest that miR-155 expression positively correlates with T-cell activation, especially in CHB patients, and is a potential biomarker for immune activation and disease progression in HBV infection.

[Clinical observation of the changes of serum helper T-lymphocytes (TH) cytokines in patients with HIV-infection and opportunistic infection].

OBJECTIVE: To observe the changes of serum helper T-Lymphocyte (Th) cytokines at each stage in patients with human immunodeficiency virus (HIV) infection and with opportunistic infection. METHODS: Seventeen normal subjects were studied as controls. Among the 85 patients with HIV-infection studied, 31 had opportunistic infection. The study was divided into stage A, B, and C according to the standards set forth by The US Centers for Disease Control and Prevention (CDC). 17, 29, and 39 subjects were respectively at stage A, B, and C. The levels of the CD4+ T cells and the CD8+ T cells were measured by flow cytometry (FCM), while the levels of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured using enzyme-linked immunosorbent assay (ELISA). All data were analyzed with statistic software SPSS11.0. RESULTS: The level of the CD4+ T cells was (361.85 +/- 230.61) 10(6)/L in the experimental group, lower than that of the control group (772.41 +/- 161.56) 10(6)/L (t = 6.992, P < 0. 01). The level of IL-2 was (61.82 +/- 63.59) pg/ml, lower than that of the control group (111.25 +/- 66.14) pg/ml (t = 2.907, P < 0.01). In the experimental group, the level of the CD8+ T cells was 713.36 +/- 317.59 10(6)/L, higher than that of the control group (583.24 +/- 96.28) 10(6)/L (t = 3.127, P < 0.01), the level of IL-10 was (1362.70 +/- 869.49) pg/ml, higher than that of the control group (818.54 +/- 276.22) pg/ml (t = 4.704, P < 0.01), and the level of IL-6 was (1883.14 +/- 1058.61) pg/m, higher than that of the control group [(1208.52 +/-745.36) pg/ml] (t = 2.502, P < 0.05). Along with the progression of the disease, the level of IL-2 in the experimental group was decreasing gradually, reaching (51.72 +/- 62.28) pg/ml at stage C and (69.02 +/- 62.77) pg/ml at stage B, both of which were lower than those of the control group. The levels of IL-6 and IL-10 rose gradually and were (2040.27 +/- 1078.95) pg/ml and (1472.10 +/-982.03 ) pg/ml respectively at stage C, higher than those of the control group. At stage B, the level of IL-10 was (1347.35 +/- 780.95) pg/ml, higher than that of the control group (818.54 +/- 276.22) pg/ml. The level of IL-6 was (2236.24 +/- 1052.42) pg/ml in patients with opportunistic infection, higher than that in those without opportunistic infection (1680.43 +/- 1017.05) pg/ml (t = 2. 395, P < 0. 05). CONCLUSION: Dynamical measure of the levels of the serum IL-2, IL-6 and IL-10 in patients with HIV infection is a must. Therefore, the progression of AIDS can be controlled by increasing the level of IL-2, decreasing the levels of IL-6 and IL-10, and adjusting the balance of TH1/TH2 cells.

Involvement of the Toll-Like Receptor/Nitric Oxide Signaling Pathway in the Pathogenesis of Cervical Cancer Caused by High-Risk Human Papillomavirus Infection.

Human papillomavirus (HPV) can activate Toll-like receptor (TLR)/nitric oxide (NO) signaling pathways; however, whether the TLR/NO pathway is involved in cervical cancer caused by high-risk HPV (HR-HPV) remains unclear. In this study, 43 HR-HPV-positive patients with cervical cancer (CC group), 39 HR-HPV-positive patients with a healthy cervix (HR-HPV group), and 33 HR-HPV-negative controls were recruited. NO concentration in cervical canal and expression of inducible NO synthase (iNOS) in cervical tissues were detected. Expressions of key TLR/NO pathway genes (TLR3/4/7/8, NF-κB p65, and iNOS) in cervical epithelial cells were detected by quantitative reverse transcription PCR. Expressions of TLR4, NF-κB p65, and iNOS in CaSki, HeLa, and C33a cells were determined by Western blot. NO concentration in cervical canal of CC group was significantly higher than in other groups (P < 0.05). Positive rates of iNOS in cervical tissues were 72.1%, 28.2%, and 3.1% in the CC group, HR-HPV group, and controls, respectively (P < 0.05). Levels of TLR3, TLR4, TLR7, TLR8, NF-κB p65, and iNOS in cervical epithelial cells were higher in CC group than in other groups (P < 0.05). Both mRNA and protein levels of TLR4, NF-κB p65, and iNOS were higher in HPV-positive HeLa and CaSki cells than in HPV-negative C33a cells (P < 0.05). Together, these results suggest that TLR/NO signaling pathway may be involved in pathogenesis of cervical cancer caused by HR-HPV.

XB130 enhances invasion and migration of human colorectal cancer cells by promoting epithelial­mesenchymal transition.

The expression of XB130 is associated with invasion and migration of many tumor cells, but its roles in human colorectal cancer (CRC) remains unknown. To investigate this, protein expression levels of XB130 in numerous human CRC cell lines were compared with a normal colorectal mucosa cell line by western blotting. Knockdown of XB130 using small interfering (si)RNA was performed to assess the effects on cell invasion and migration in a Transwell assay and a scratch test. Western blotting was also used to quantify the levels of proteins associated with epithelial­mesenchymal transition (EMT), including E­cadherin, vimentin, phosphorylated (p)­protein kinase B (AKT), p­forkhead homeobox type O 3a (FOXO3a) and zinc finger E­box­binding homeobox 1 (ZEB­1). The relative expression of XB130 protein was significantly higher in CRC cells compared with control cells (P<0.01). Knockdown of XB130 using siRNA significantly decreased the invasive and migratory responses of CRC cells (P<0.01). In addition, levels of E­cadherin were increased, while vimentin, p­AKT, p­FOXO3a and ZEB­1 were decreased (P<0.01). In conclusion, the present study demonstrated that the expression of XB130 is elevated in CRC cells. Loss of XB130 was associated with decreased invasion and migration of CRC cells, possibly as a result of EMT inhibition. Thus, upregulation of XB130 may underlie some of the tumorigenic events observed in human CRCs. XB130 may be a promising target for CRC therapy in humans; further mechanistic studies exploring the function of XB130 in CRC cells are warranted.

CD127 Expression in Naive and Memory T Cells in HIV Patients Who Have Undergone Long-Term HAART.

OBJECTIVE: To evaluate cluster of differentiation (CD)127 expression in T cells of patients with HIV-1 and the relationship of CD127 expression with disease progression. METHODS: We divided 139 patients infected with human immunodeficiency virus type 1 (HIV-1) who had undergone highly active antiretroviral therapy (HAART) into 3 groups: patients with poor recovery (CD4+T < 350/µ;L, patients with general recovery (CD4+T = 350 - ∼600/µL) and patients with good recovery (CD4+T > 600/µL). Counts and percentages of naïve (CD45RA+) and memory (CD45RO+) T cells and CD127 expression were determined using flow cytometry. RESULTS: CD4+CD45RO+, CD4+CD45RA+, CD4+ CD45RO+ CD127+, and CD4+CD45RA+CD127+T-cell counts in patients with good recovery were higher than in patients with poor recovery and those with general recovery patients (P <.05). Percentages of CD45RO+ were increased, and percentages of CD45RA+ and CD127 in T cells were decreased in patients with poor and general recovery (P <.05). CD127 values were positively correlated with CD4+T-cell counts and percentages of CD45RA+ subsets (P <.05). CONCLUSION: CD127 expression in T cells is decreased in patients with HIV-1 and is related to recovery of CD4+T-cell counts and to naïve subsets.