MicroRNAs are small non-coding RNA molecules that play essential roles in biological processes ranging from cell cycle to cell migration and invasion. Accumulating evidence suggests that miR-34a, as a key mediator of p53 tumor suppression, is aberrantly expressed in human cancers. In the present study, we aimed to explore the precise biological role of miR-34a and the global protein changes in HCC cell line HepG2 cells transiently transfected with miR-34a. Transfection of miR-34a into HepG2 cells caused suppression of cell proliferation, inhibition of cell migration and invasion. It also induced an accumulation of HepG2 cells in G1 phase. Among 116 protein spots with differential expression separated by 2-DE method, 34 proteins were successfully identified by MALDI-TOF/TOF analysis. Of these, 15 downregulated proteins may be downstream targets of miR-34a. Bioinformatics analysis produced a protein-protein interaction network, which revealed that the p53 signaling pathway and cell cycle pathway were two major hubs containing most of the proteins regulated by miR-34a. Cytoskeletal proteins such as LMNA, GFAP, MACF1, ALDH2, and LOC100129335 are potential targets of miR-34a. In conclusion, abrogation of miR-34a function could cause downstream molecules to switch on or off, leading to HCC development.

Aim. The primary aim of this study is to compare the short- and long-term outcomes between ABO-incompatible (ABOi) adult living donor liver transplantation (ALDLT) with rituximab prophylaxis and ABO-compatible (ABOc) ALDLT. Background. The strategy of ABOi liver transplantation (LT) was originated initially to increase the donor pool and to enable liver transplantation in emergency conditions. However, ABOi ALDLT remains a controversial approach in comparison to ABOc ALDLT. Methods. PubMed, Embase, and the Cochrane Library study search were accomplished to recognize studies comparing ABOi and ABOc ALDLT. Meta-analyses were conducted based on the evaluation of heterogeneity using a fixed-effect model and a random-effect model to assess the short- and long-term outcomes following ABOi ALDLT with rituximab prophylaxis. Results. Nine studies comprising a total of 3,922 patients (ABOi=671 and ABOc=3,251) were identified. There was no significant difference between ABOi and ABOc groups for 1-year, 3-year, and 5-year OS and graft survival, respectively. Moreover, 1-year and 3-year OS and DFS were similar between both groups for HCC patients. However, ABOi ALDLT had higher incidences of CMV infection, AMR, overall biliary complications, and biliary stricture than ABOc ALDLT and had other comparable postoperative complications. Conclusion. Our meta-analysis included studies comparing ABOi and ABOc ALDLT after the introduction of rituximab in a desensitization protocol for ABOi ALDLT. The results of ABOi ALDLT were comparable with those of ABOc ALDLT. However, biliary complications, CMV infection, and AMR remain a concern in the era of rituximab.

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T help cell 17 (Th17), recently identified as a new subset of CD4 + T cells, has been implicated in autoimmune diseases, tumor immunity, and transplant rejection. To investigate the role of Th17 in acute hepatic rejection, a rat model of allogeneic liver transplantation (Dark Agouti (DA) to Brown Norway (BN)) was established and isogeneic liver transplantation (BN to BN) was used as controls in the study. The expression of Th17-related cytokines in the liver and peripheral blood was determined by immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), or real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Strong expression of interleukin-17A (IL-17A), IL-6, transforming growth factor-β (TGF-β), IL-8, and myeloperoxidase (MPO) was observed in liver allografts. The ratios of Th17 to CD4 + lymphocytes in the liver and peripheral blood were dramatically increased in the allograft group compared with the control (P<0.01). Secreted IL-17 and IL-6 in liver homogenate and serum were significantly elevated in the allograft group, while secreted TGF-β was increased in liver homogenate and decreased in serum compared with the control (P<0.01). The messenger RNA (mRNA) levels of IL-17, IL-21, and IL-23 were enhanced in the allografts compared with the control (P<0.01). Correlation analysis showed significant correlations between IL-17 and IL-6 and TGF-β and between IL-17 and IL-21 and IL-23. The present study demonstrates that Th17 plays a role in promoting rat liver allograft rejection.

Background: Early allograft dysfunction (EAD) is associated with decreased graft and patient survival rates. This study aimed to identify the severity of EAD and develop a predictive model for EAD after donation after circulatory death (DCD) liver transplantation (LT). Furthermore, the influence of operative time on EAD incidence was also evaluated. Methods: In this retrospective, multicentre cohort study, nomograms were established based on a singlecentre training cohort (n=321) and validated in a 3-center validation cohort (n=501). Results: The incidence rate of EAD was 46.4% (149/321) in the training cohort and 40.5% (203/501) in the validation cohort. Of the 149 EAD patients in the training cohort, 77 patients with either elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were classified as having EAD type A, and the rest of the EAD patients were classified as having EAD type B. Recipients with EAD type B had lower graft and patient survival rates than recipients with EAD type A (P=0.043 and 0.044, respectively). We further developed a nomogram to predict EAD (graft weight, cold ischemia time, donor age, model for endstage liver disease (MELD) score) and another nomogram to predict EAD type B (graft weight, cold ischemia time, MELD score). The nomograms for the prediction of EAD and EAD type B had good discrimination [concordance index (C-index) =0.712 (0.666-0.758), 0.707 (0.641-0.773)] and calibration [Hosmer-Lemeshow (HL) P=0.384, P=0.425] in the validation cohort. An increased operative time (>6 h) was associated with increased EAD and EAD type B incidence in the high-risk group (P=0.005, P=0.020, respectively).Conclusions: EAD type B was associated with decreased graft and patient survival rates. The novel nomograms effectively predicted the incidence of EAD and EAD type B in DCD LT patients.