Overexpression of miR-4669 Enhances Tumor Aggressiveness and Generates an Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma: Its Clinical Value as a Predictive Biomarker.

Accumulating evidence suggests the involvement of tumor-derived exosomes in the development and recurrence of hepatocellular carcinoma (HCC). We previously identified miR-4669 as a highly expressed microRNA in circulating exosomes obtained from patients with post-transplant HCC recurrence. This study aimed to explore how overexpression of miR-4669 affects HCC development and recurrence.

Circulating exosomal miR-92b: Its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence.

A recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) is one of the major concerns reflecting the higher mortality of HCC. This study aimed to explore the impact of circulating exosomes on HCC development and recurrence. One-shot transfusion of hepatoma serum to naïve rats induced liver cancer development with gradual elevation of alpha-fetoprotein (AFP), but exosome-free hepatoma serum failed to induce AFP elevation.

A novel moonlight function of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for immunomodulation.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an energy metabolism-related enzyme, which generates NADH in glycolysis. Our previous study revealed a novel role of exogenous GAPDH in the amelioration of lipopolysaccharide (LPS)-induced sepsis-related, severe acute lung injury (ALI) in mice. Here, we show the effect of extracellular GAPDH on the physiological functions of macrophages, which play an important role in the onset of sepsis and ALI.

Hepatic miR-301a as a Liver Transplant Rejection Biomarker? And Its Role for Interleukin-6 Production in Hepatocytes.

Acute rejection (AR) of liver transplantation remains a formidable challenge for diagnostic medicine and biomarker discovery. We characterized AR-related microRNAs (miRNAs) and the underlying AR mechanisms in liver transplantation. Using a rat model of orthotopic liver transplantation (OLT) as well as microarrays, we compared the miRNA expression profiles between naive and AR livers on day 7 after OLT with short- (<14 days, donor Dark Agouti [DA] liver into Lewis [LEW] recipient) and long-term (>60 days, donor DA liver into Piebald Virol Glaxo [PVG] recipient) survival fates.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) prevents lipopolysaccharide (LPS)-induced, sepsis-related severe acute lung injury in mice.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an energy metabolism-related enzyme in the glycolytic pathway. Recently, it has been reported that GAPDH has other physiological functions, such as apoptosis, DNA repair and autophagy. Some in vitro studies have indicated immunological aspects of GAPDH function, although there is no definite study discussing the advantage of GAPDH as a therapeutic target.

Induction of antinuclear antibodies by de novo autoimmune hepatitis regulates alloimmune responses in rat liver transplantation.

Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance.

Biological interactions of CYP2C19 genotypes with CYP3A4*18, CYP3A5*3, and MDR1-3435 in living donor liver transplantation recipients.

Background: Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. The CYP3A4*18, CYP3A5*3, and MDR1-3435 variant alleles are very important, particularly in tacrolimus metabolism in organ transplant rejection.

Aim: The aim of this study is o explore possible interactions among different CYP2C19 genotypes, namely, between homozygous extensive metabolizers (HomEM), heterozygous extensive metabolizers (HetEM), and poor metabolizers (PM), and the CYP3A4*18, CYP3A5*3, and MDR1-3435 variants in living donors and patients who received a living donor liver transplant (LDLT).

Western blotting analysis for quantitative detection of CYP2C19 expression in liver tissues in the setting of living donor liver transplantation.

Background: The cytochrome P450 (CYP) drug-metabolizing enzymes play an important role in cellular metabolism. Therapeutic failure or drug toxicity in the period after liver transplantation (LT) is influenced by the drug metabolizing capacity of the graft. The expression levels of CYP2C19 enzyme are often used as an indicator of the functioning of the CYP system.

Homogenous phenomenon of graft liver CYP2C19 genotypes after living donor liver transplantation.

Background: The donor liver grafts with different allelic patterns do not affect CYP2C19 genotypes in the peripheral blood of living donor liver transplantation (LDLT) recipients.

Aim: This study investigated the influence of graft liver CYP2C19 genotypes on recipients who received the same or different CYP2C19 genotypes from donors after LDLT.

Methods: There were 30 donors and 30 recipients with the same CYP2C19 genotypes and 47 donors and 47 recipients with different CYP2C19 genotypes.

Influence of CYP2C19 genotypes on graft pathological findings and postoperative liver function in recipients after living-donor liver transplantation.

Background: New graft cytochrome P450 2C19 (CYP2C19) should have different characteristics after living-donor liver transplantation (LDLT). We prospectively investigated the influence of genotypes of CYP2C19 in liver graft pathological finding (GPF) and postoperative liver function (POLF) of recipients after LDLT.

Material/methods: Among 60 consecutive patients who underwent LDLT, 36 recipients developed sudden-onset abnormal liver function and required liver biopsy, while the remaining 24 recipients did not require biopsy.

Donor graft does not affect the P450 2C19 genotype expressed in peripheral blood in recipients of living donor liver transplantation.

The function of cytochrome P450 2C19 (CYP2C19) is altered in patients with end-stage liver disease (ESLD) that require liver transplantation (LT). The status of CYP2C19 is of considerable interest because the transplanted healthy donor livers are perfused with the blood of the recipient with ESLD. This study aims to clarify the changes in CYP2C19 in the peripheral blood before and after LT.

Prolongation of heart allograft survival of rats treated by a Th2 inhibitor.

In terms of Th1/Th2 balance in response to signals given during donor antigen presentation, induction of tolerance is more often correlated with Th2-type than with Th1-type reactions. However, in our study, heart allograft survival was prolonged by treatment of rats with a Th2 inhibitor. Suplatast tosilate (IPD; Taiho; Tokyo, Japan) is a novel immunoregulator that suppresses IgE production and eosinophil infiltration through selective inhibition of interleukin (IL)-4 and IL-5 synthesis by Th2-like cells but not IFN-gamma production in Th1 cells.