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.

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.

It has been reported that hypereosinophilic syndrome may be induced by antituberculosis drugs. We herein report the case of a 43-year-old man who had been on antituberculosis drugs for two months to treat tuberculous meningitis. During therapy, he suffered from drug rash with eosinophilia and systemic symptoms (DRESS) presenting as acute eosinophilic myocarditis, as confirmed on a histopathologic examination. According to the patient's medication history, clinical features and accessory examination findings, the eosinophilic myocarditis was thought to be possibly induced by isoniazid. Although further investigations are needed to confirm causality, isoniazid may be added to the list of drugs with the potential to cause DRESS syndrome.

Abstract. Activation of hepatic stellate cells (HSCs) is a pivotal event during hepatic fibrogenesis. Activated HSCs are the main source of collagen and other extracellular matrix (ECM) components, and emerging antifibrotic therapies are aimed at preventing ECM synthesis and deposition. MicroRNAs (miRNAs) have been demonstrated to exert regulatory effects on HSC activation and ECM synthesis. In the present study, the HSC-T6 rat hepatic stellate cell line was transiently transfected with a miRNA (miR)-203 mimic, which is an artificial miRNA that enhances the function of miR-203, with a miR-203 inhibitor or with a scramble miRNA negative control. mRNA and protein expression levels of collagen (COL) 1A1, COL3A1, α-smooth muscle actin (α-SMA) and mothers against decapentaplegic homolog 3 (SMAD3) were assessed using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The interaction between miR-203 and the 3'-untranslated region (UTR) of SMAD3 mRNA was examined using a dual-luciferase reporter assay. The proliferative capabilities of activated HSCs were measured using an MTT assay. The present results demonstrated that the mRNA and protein expression levels of COL1A1, COL3A1, α-SMA and SMAD3 were significantly upregulated following transfection of HSC-T6 cells with the miR-203 inhibitor. Conversely, COL1A1, COL3A1, α-SMA, and SMAD3 mRNA and protein expression appeared to be downregulated in rat HSCs transfected with miR-203 mimics. Notably, the inhibition of miR-203 expression was revealed to promote HSC proliferation, whereas increased miR-203 expression suppressed the proliferative capabilities of HSC-T6 cells. Furthermore, SMAD3 was revealed to be a direct target of miR-203. The present study suggested that miR-203 may function to prevent the synthesis and deposition of ECM components, including COL1A1, COL3A1 and α-SMA, and to inhibit the proliferation of HSCs through a SMAD3-dependent mechanism. Therefore, it may be hypothesized that miR-203 has potential as a novel target for the development of alternative therapeutic strategies for the treatment of patients with hepatic fibrosis in clinical practice.

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