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Chemokine production by epithelial cells is important for neutrophil recruitment during viral infection, the appropriate regulation of which is critical for restraining inflammation and attenuating subsequent tissue damage. Epithelial cell expression of long noncoding RNAs (lncRNAs), RNA-binding proteins, and their functional interactions during viral infection and inflammation remain to be fully understood. Here, we identified an inducible lncRNA in the Cxcl2 gene locus, lnc-Cxcl2, which could selectively inhibit Cxcl2 expression in mouse lung epithelial cells but not in macrophages. lnc-Cxcl2-deficient mice exhibited increased Cxcl2 expression, enhanced neutrophils recruitment, and more severe inflammation in the lung after influenza virus infection. Mechanistically, nucleus-localized lnc-Cxcl2 bound to Cxcl2 promoter, recruited a ribonucleoprotein La, which inhibited the chromatin accessibility of chemokine promoters, and consequently inhibited Cxcl2 transcription in cis. However, unlike mouse lnc-Cxcl2, human lnc-CXCL2-4-1 inhibited multiple immune cytokine expressions including chemokines in human lung epithelial cells. Together, our results demonstrate a self-protecting mechanism within epithelial cells to restrain chemokine and neutrophil-mediated inflammation, providing clues for better understanding chemokine regulation and epithelial cell function in lung viral infection. [ABSTRACT FROM AUTHOR]

Adipose tissue-derived mesenchymal stem cells (ADSCs) have been considered to be attractive and readily available adult mesenchymal stem cells, and they are becoming increasingly popular for use in regenerative cell therapy, as they are readily accessible through minimally invasive techniques. The present study investigated whether autologous ADSC transplantation promoted liver regeneration following a repeat partial hepatectomy in rats. The rats were divided into three groups as follows: 70% partial hepatectomy (PH) group; repeat PH (R-PH) group and R-PH/ADSC group, subjected to R-PH and treated with autologous ADSCs via portal vein injection. In each group, the rats were sacrificed at different time points postoperatively in order to evaluate the changes in liver function and to estimate the liver regenerative response. The expression of proliferating cell nuclear antigen (PCNA) labeling index in the liver was measured using immunohistochemistry. The expression levels of hepatocyte growth factor (HGF) mRNA were measured using reverse transcription polymerase chain reaction. The results showed that regeneration of the remaining liver following R-PH was significantly promoted by ADSC transplantation, as shown by a significant increase in liver to body weight ratio and the PCNA labeling index at 24 h post-hepatectomy. Additionally, ADSC transplantation markedly inhibited the elevation of serum levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin, increased HGF content and also attenuated hepatic vacuolar degeneration 24 h postoperatively. Furthermore, the liver was found to almost fully recover from hepatocellular damage due to hepatectomy among the three groups at 168 h postoperatively. These results indicated that autologous ADSC transplantation enhanced the regenerative capacity of the remnant liver tissues in the early phase following R-PH. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC)-based cancer immunotherapy requires an immunogenic tumor-associated antigen and an effective therapeutic strategy. Glypican 3 (GPC3) is a valuable diagnostic marker and a potential therapeutic target in hepatocellular carcinoma (HCC). The present study investigated whether DCs transduced with the GPC3 gene (DCs-GPC3) and co-cultured with autologous cytokine-induced killer cells (CIKs) may induce a marked specific immune response against GPC3-expressing HCC cells in vitro and in vivo. Human DCs were transfected with a green fluorescent protein plasmid with GPC3 by nucleofection and then co-cultured with autologous CIKs. Flow cytometry was used to measure the phenotypes of DCs and CIKs. The co-cultured cells were harvested and incubated with HCC cells and the cytotoxicity of the CIKs was assessed by nonradioactive cytotoxicity assay. The anti-tumor activity of these effector cells was further evaluated using a nude mouse tumor model. The results demonstrated that DCs-GPC3 significantly promoted the autologous CIKs differentiation, as well as anti-tumor cytokine interferon-γ secretion. In addition, DCs-GPC3-CIKs significantly enhanced the cytotoxic activity against GPC3-expressing HepG2 cells, indicating a GPC3-specific marked immune response against HCC cells. The in vivo data indicated that DCs-GPC3-CIKs exhibited significant HepG2 cell-induced tumor growth inhibition in nude mice. The results of the present study provided a new insight into the design of personalizing adoptive immunotherapy for GPC3-expressing HCC cells. [ABSTRACT FROM AUTHOR]

The present case report describes the diagnosis and treatment of a patient with veno-occlusive disease (VOD) following liver transplantation. Combining the clinical data and relevant literature, the study aimed to consider the causes of VOD following liver transplantation, and the pathogenesis, clinical diagnosis and auxiliary examination features of VOD. A 42-year-old man who had a long history of taking traditional Chinese medicine (essential components unknown) underwent an orthotropic liver transplantation on January 14, 2011, due to small venous occlusion disease of the liver. The patient was treated with tacrolimus as an antirejection therapy following the surgery, and gradually developed right upper quadrant pain and fatigue. The examination results were consistent with the diagnostic standards for VOD. Following treatment with methylprednisolone, the patient was treated with alprostadil and Danhong injections. Forty days later, the patient's total bilirubin (TBIL) level was observed to have decreased significantly, the liver function had returned to normal and the ascites had decreased, but had not completely disappeared. The patient then underwent a transjugular intrahepatic porto-systemic shunt (TIPS) procedure, following which the ascites were shown to have completely disappeared. [ABSTRACT FROM AUTHOR]

Background: A precise predictive survival model of liver transplantation (LT) with antiviral prophylaxis for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and cirrhosis has not been established. The aim of our study was to identify predictors of outcome after LT in these patients based on tumor staging systems, antitumor therapy pre-LT, and antiviral prophylaxis in patients considered to be unfit by Milan or UCSF criteria. Methods: From 2002 to 2008, 917 LTs with antiviral prophylaxis were performed on patients with HBV-cirrhosis, and 313 had concurrent HCC. Results: Stratified univariate and multivariate analyses demonstrated that independent predictors for poor survival were tumor size >7.5 cm (P = 0.001), tumor number >1 (P = 0.005), vascular invasion (P = 0.001), pre-LT serum alpha-fetoprotein (AFP) level &⩽10878;1000 ng/ml (P = 0.009), and pre-LT aspartate aminotransferase (AST) level &⩽10878;120 IU/L (P = 0.044). Pre-LT therapy for HCC was an independent predictor of better survival (P = 0.028). Based on CLIP and TNM tumor staging systems, HCC patients with HBV-cirrhosis who met the following criteria: solitary tumor ⩽7.5 cm, or ⩽4 multifocal nodules, the largest lesion ⩽5 cm and total tumor diameter ⩽10 cm, or more nodules with the largest lesion ⩽3 cm, and pre-LT serum AFP level <1000 mg/L and AST level <120 IU/L without vascular invasion and lymph node metastasis who were unfit for UCSF, had survival rates of 89% at 5 years. There was a 47% 5-year survival rate for patients with HCC exceeding the revised criteria. Conclusions: The current criteria for LT based on tumor size, number and levels of AFP and AST may be modestly expanded while still preserving excellent survival after LT. The expanded criteria combined with antiviral prophylaxis and pre-LT adjuvant therapy for HCC may be a rational strategy to prolong survival after LT for HCC patients with HBV-associated cirrhosis. [ABSTRACT FROM AUTHOR]

Variations in the activities of Cytochrome P450s are one of the major factors responsible for inter-individual differences in drug clearance rates, which may cause serious toxicity or inefficacy of therapeutic drugs. Various mRNA level is one of the key factors for different activity of the major P450 genes. Although both genetic and environmental regulators of P450 gene expression have been widely investigated, few studies have evaluated the functional importance of cis- and trans-regulatory factors and environmental factors in the modulation of inter-individual expression variations of the P450 genes. In this study, we measured the mRNA levels of seven major P450 genes (CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5) in 96 liver biopsy samples from Chinese population. Both trans-acting (mRNA levels and non-synonymous SNPs of putative regulator genes) and cis-acting (gene copy number and functional SNPs) factors were investigated to identify the determinants of the expression variations of these seven P450 genes. We found that expression variations of most P450 genes, regulator genes and housekeeping genes were positively correlated at the mRNA level. After partial correlation analysis using ACTB and GAPDH expression to eliminate the effect of global regulators, a UPGMA (Unweighted Pair Group Method with Arithmetic Mean) tree was constructed to reveal the effects of specific regulation networks potentially masked by global regulators. Combined with the functional analysis of regulators, our results suggested that expression variation at the mRNA level was mediated by several factors in a gene-specific manner. Cis-acting genetic variants might play key roles in the expression variation of CYP2D6 and CYP3A5, environmental inducers might play key roles in CYP1A1 and CYP1A2 variation and global regulators might play key roles in CYP2C9 variation. In addition, the functions of regulators that play less important roles in controlling expression variation for each P450 gene were determined. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to quantitatively monitor the response of CD95 molecules expressed on CD3+ T cells (CD95+CD3+ cells) and CD38 molecules expressed on CD8+ T cells (CD38+CD8+ cells) to ganciclovir treatment after orthotopic liver transplant (OLT) in recipients with active human cytomegalovirus (HCMV) infection. Methods: Blood samples were collected from 20 liver transplanted recipients with active HCMV infection and 24 recipients without HCMV infection. CD95+CD3+ cells and CD38+CD8+ cells were quantitatively detected with QuantiBRITE bead methods by dual-color flow cytometry analysis during the post-transplantation period. Results: CD95+CD3+ cells and CD38+CD8+ cells were not significantly different among different ages of healthy adults ( P > 0.05). CD95+CD3+ cells and CD38+CD8+ cells were drastically increased in the active HCMV infection group compared with that in the stable group or in the healthy group ( P < 0.001), and then they were gradually decreased within the next several weeks after ganciclovir treatment when compared with active HCMV infection recipients ( P < 0.001). Conclusions: The present study showed that CD38+CD8+ T cells can be an appropriate immunological marker for early detection and antiviral therapeutic monitoring of HCMV infection. The evaluation of CD95 molecule levels may be used routinely in clinical practice to assess the level of immunosuppression. [ABSTRACT FROM AUTHOR]

A letter to the editor which discusses the effectiveness of the antiviral Tenofir disoproxil fumarate (TDF) which reduces the probability of Hepatitis B virus (HBV) recurrence is presented in the 2014 issue of the journal "Transplant International."