Shun-Lan Ni

The role of extracellular vesicles in mediating progression, metastasis and potential treatment of hepatocellular carcinoma

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.

Isoniazid-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Presenting as Acute Eosinophilic Myocarditis

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 patients 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.

Splenic CD11c(low)CD45RB(high) dendritic cells derived from endotoxin-tolerant mice attenuate experimental acute liver failure.

Endotoxin tolerance (ET) is suggested to attenuate the severity of acute liver failure (ALF) in mice, possibly through both innate and adaptive immunity. However, the involvement of regulatory dendritic cells (DCregs) in ET has not been fully elucidated. In this study, their effect on ALF in mice was investigated. Splenic DCregs from ET-exposed mice (ET-DCregs) showed lower expression levels of CD40, CD80, and MHC-II markers and stronger inhibition of allogenic T cells and regulation of IL-10 and IL-12 secretion than splenic DCregs from normal mice (nDCregs). Moreover, the mRNA and protein levels of TNF-α and P65 in splenic ET-DCregs were significantly lower than those in the splenic nDCregs. The survival rate was significantly increased and liver injury was mitigated in mice with ALF treated with splenic ET-DCregs. In addition, A20 expression was decreased in the liver of ALF mice, but elevated after infusion of splenic nDCregs and ET-DCregs, and a much higher elevation was observed after infusing the latter cells. The functionality of splenic DCregs was altered after ET exposure, contributing to protection of the livers against D-GalN/LPS-induced ALF.

Dendritic cells with increased expression of suppressor of cytokine signaling 1(SOCS1) gene ameliorate lipopolysaccharide/d-galactosamine-induced acute liver failure

HighlightsDendritic cells with overexpression of SOCS1 are constructed with lentivirus encoding SOCS1.SOCS1 could block maturation process of Dendritic cells through inhibition of JAK/STAT pathway signaling.Dendritic cells with increased expression of SOCS1 could ameliorate LPS/D‐GalN induced acute liver failure. &NA; Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/d‐galactosamine induced acute liver failure via inhibition of TLR4 pathway.