Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC. Exosomal miRNAs derived from HCC cells can enhance transformed cell growth in recipient cells by modulating the expression of transforming growth factor-β activated kinase-1(TAK1) and downstream signaling molecules. Furthermore, vacuolar protein sortin 4 homolog A(VPS4A) and insulin-like growth factor(IGF)-1 regulate exosome-mediated miRNAs transfer. Immune cells- derived EVs containing integrin αMβ2 or CD147 may facilitate HCC metastasis. In addition, EVs-mediated shuttle of long non-coding RNAs (lncRNAs), specifically linc- VLDLR and linc-ROR promote chemoresistance of malignant cells. Heat shock proteins (HSPs)-harboring exosomes derived from HCC tumor cells increase the antitumor effect of natural killer (NK) cells, thus enhancing HCC immunotherapy. Indeed, inhibition of HCC tumor growth has been associated with tumor cell-derived exosomes (TEX)-pulsed dentritic cells (DCs). Exosomes are also essential in liver metastasis during colorectal carcinoma (CRC) and pancreatic ductal adenocarcinomas (PDAC). Therefore, as nucleic acid and drug delivery vehicles, EVs show a tremendous potential for effective treatment against HCC.

Kinesin family member 20A (KIF20A) is an essential regulator of cytokinesis. In this study, by performing a retrospective study based on data from the Cancer Genome Atlas (TCGA)-Liver and Hepatocellular Carcinoma (LIHC) cohort, we tried to assess the independent prognostic value of KIF20A in terms of overall survival (OS) and recurrence-free survival (RFS). Results showed that normal liver tissues had very low KIF20A expression compared with normal tissues in other cohorts in TCGA. However, the primary HCC tissues (N = 371) had significantly elevated KIF20A expression than normal liver tissues (N = 50). Immunohistochemistry (IHC) data showed that normal hepatocytes had weak KIF20A staining. In comparison, some HCC tissues had medium and strong KIF20A expression, with nuclear-enhanced staining. By grouping patients with primary HCC (N = 365) into high and low KIF20A expression groups, we found that the high expression group had a substantially higher proportion of high-grade tumors (G3/G4) (34/65, 52.3% vs. 96/295, 32.5%, P = 0.0027), advanced tumors (stage III/IV) (28/61, 45.9% vs. 59/280, 21.1%, P < 0.0001) and death (44/67, 65.7% vs. 86/298, 28.9%, P < 0.0001) compared with the low expression group. Kaplan-Meier curves of OS and RFS indicated that high KIF20A expression was associated with worse survival outcomes. Subgroup analysis confirmed the associations in G1/G2, G3/G4 tumors and in early and advanced stages. Following univariate and multivariate analysis revealed that KIF20A expression was an independent prognostic indicator for poor OS (HR: 1.304, 95%CI: 1.157-1.469, P < 0.001) and RFS (HR: 1.144, 95%CI: 1.028-1.272, P < 0.001). Based on these findings, we infer that KIF20A was aberrantly expressed in HCC tissues and its expression might independently predict poor OS and RFS. © 2018 IUBMB Life, 70(4):328-335, 2018.

Aim To explore the therapeutic effects and mechanisms of interleukin 10 gene-modified bone marrow-derived dendritic cells (DC-IL10) on liver fibrosis. Methods In vitro, BMDCs were transfected with lentiviral-interleukin 10-GFP (LV-IL10-GFP) at the MOI of 1 : 40. Then, the phenotype (MHCII, CD80, and CD86) and allo-stimulatory ability of DC-IL10 were identified by flow cytometry, and the levels of IL-10 and IL-12 (p70) secreted into the culture supernatants were quantified by ELISA. In vivo, DC-IL10 was injected into mice with CCl4-induced liver fibrosis through the tail vein. Lymphocytes were isolated to investigate the differentiation of T cells, and serum and liver tissue were collected for biochemical, cytokine, histopathologic, immune-histochemical, and Western blot analyzes. Results In vitro, the expressions of MHCII, CD80, and CD86 in DC-IL10 were significantly suppressed, allogeneic CD4+T cells incubated with DC-IL10 showed a lower proliferative response, and the levels of IL-10 and IL-12 (p70) secreted into the DC-IL10 culture supernatants were significantly increased and decreased, respectively. In vivo, regulatory T cells (Tregs) were significantly increased, while ALT, AST, and inflammatory cytokines were significantly reduced in the DC-IL10 treatment group, and the degree of hepatic fibrosis was obviously reversed. The TGF-β/smad pathway was inhibited following DC-IL10 treatment compared to the liver fibrosis group. Conclusion IL-10 genetic modification of BMDCs may maintain DC in the state of tolerance and allow DC to induce T cell hyporesponsiveness or tolerance. DC-IL10 suppressed liver fibrosis by inducing Treg production and inhibiting the TGF-β/smad signaling pathway.

Aims. Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are similar in many respects during their acute exacerbation; however, ACLF generally has a poorer prognosis. We aimed to investigate the role and dynamic changes of regulatory T cell (Treg) and T helper 17 (Th17) cell proportions during ACLF progress. Methods. All rats were classified into two groups randomly: ACLF group and ALF group (control group). The rat model of ACLF was preestablished by intraperitoneal injection of carbon tetrachloride for 2 months. Then acute liver injury was induced by combined D-galactosamine and lipopolysaccharide. Six time points were examined before or after acute induction. Liver samples were performed with hematoxylin-eosin and Masson staining; circulatory Treg and Th17 cell frequencies were determined using flow cytometry assays; serum levels of alanine aminotransferase, aspartate aminotransferase, interleukin-10 (IL-10), and interferon-γ (IFN-γ) were examined. Results. In group ACLF, both Th17 cell proportion and IFN-γ level presented upgrade firstly and then descend latter tendency; the trends of Treg cell proportion and IL-10 level were observed to gradually decrease and became stable. Conclusion. The Treg cells played an important role in the immunologic mechanism during the process of ACLF. And the function of Treg cells in ACLF was defective.

A simulation model based on parallel systems is established, aiming to explore the relation between the number of submissions and the overall quality of academic journals within a similar discipline under peer review. The model can effectively simulate the submission, review and acceptance behaviors of academic journals, in a distributed manner. According to the simulation experiments, it could possibly happen that the overall standard of academic journals may deteriorate due to excessive submissions.

Bigger and better: The new thin-film organic material octabenzcircumbiphenyl (OBCB; see scheme) forms an active layer in a field effect transistor, which can be switched simultaneously with two different inputs, that is, electrical bias and protonation.

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The research in the present paper focuses on decoupling the six-degrees-of-freedom motions of a magnetically levitated stage with moving coils and controlling the levitation motion. The decoupling is based on commutation of coil array, which is obtained reversely from the electromagnetic force/torque model of the stage. The control of levitation motion is carried out by a phase lead-lag controller designed on the criterion of minimum integral of time-weighted absolute error after gravity compensation modeling of the plant dynamics. Comprehensive simulations of the control system in MATLAB/Simulink and real levitation experiments on a digital signal processor-centered test platform are made to verify the six-degrees-of-freedom decoupling effect and the closed-loop control performances of the levitation degree of freedom. The results indicate that the six-degrees-of-freedom motions of the stage can be decoupled through coil array commutation and the levitation motion can be controlled by the phase lead-lag controller based on the gravity compensation model and designed on the criterion of minimum integral of time-weighted absolute error.