RESUMO
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a severe state of non-alcoholic fatty liver disease (NAFLD), which is pathologically characterised by steatosis, hepatocyte ballooning, and lobular inflammation. Host-microbial interaction has gained attention as one of the risk factors for NASH. Recently, cnm-gene positive Streptococcus mutans expressing cell surface collagen-binding protein, Cnm (cnm-positive S. mutans), was shown to aggravate NASH in model mice. Here, we assessed the detection rate of cnm-positive S. mutans in oral samples from patients with NASH among NAFLD. METHODS: This single hospital cohort study included 41 patients with NAFLD. NASH was diagnosed histologically or by clinical score. The prevalence of cnm-positive S. mutans, oral hygiene and blood tests, including liver enzymes, adipocytokines and inflammatory and fibrosis markers, were assessed in biopsy-proven or clinically suspected NASH among NAFLD. RESULTS: Prevalence of cnm-positive S. mutans was significantly higher in patients with NASH than patients without NASH (OR 3.8; 95% CI 1.02 to 15.5). The cnm-positive S. mutans was related to decreased numbers of naturally remaining teeth and increased type IV collagen 7S level (median (IQR) 10.0 (5.0-17.5) vs 20.0 (5.0-25.0), p=0.06; 5.1 (4.0-7.9) vs 4.4 (3.7-5.3), p=0.13, respectively). CONCLUSIONS: Prevalence of cnm-positive S. mutans in the oral cavity could be related to fibrosis of NASH among NAFLD.
RESUMO
The present study aimed to establish a novel efficient nonviral strategy for suicide gene transfer in hepatocellular carcinoma (HCC) in vivo. We employed branched polyethylenimine (PEI) and combined it with Epstein-Barr virus (EBV)-based plasmid vectors. The HCC cells transfected with an EBV-based plasmid carrying the herpes simplex virus-1 thymidine kinase (HSV-1 Tk) gene (pSES.Tk) showed up to 30-fold higher susceptibilities to ganciclovir (GCV) than those transfected with a conventional plasmid vector carrying the HSV-1 Tk gene (pS.Tk). The therapeutic effect in vivo was tested by intratumoral injection of the plasmids into HuH-7 hepatomas transplanted into C.B-17 scid/scid mutant (SCID) mice and subsequent GCV administrations. Treatment with pSES.Tk, but not pS.Tk, markedly suppressed growth of hepatomas in vivo, resulting in a significantly prolonged survival period of the mice. These findings suggest that PEI-mediated gene transfer system can confer efficient expression of the suicide gene in HCC cells in vivo by using EBV-based plasmid vectors.