| The first part:Hepatitis B virus(HBV) and hepatitis C virus(HCV) infections contributes to a substantial proportion of liver disease worldwide. The aim of this study was to assess the clinical and virological features of HBV-HCV co-infection.Demographic data were collected for 3238 high-risk people from an HCV-endemic region in China. Laboratory tests included HCV antibody and HBV serological markers, liver function tests, and routine blood analysis. Anti-HCV positive samples were analyzed for HCV RNA levels and subgenotypes. HBs Ag-positive samples were tested for HBV DNA. Results are as follows in the first part:A total of 1468 patients had chronic HCV and/or HBV infections. Among them, 1200 individuals were classified as HCV mono-infected, 161 were classified as HBV mono-infected, and 107 were classified as co-infected. The HBV-HCV co-infected patients not only had a lower HBV DNA positive rate compared to HBV mono-infected patients(84.1% versus 94.4%, respectively; P<0.001). The median HCV RNA levels in HBV-HCV co-infected patients were significantly lower than those in the HCV mono-infected patients(1.18[Interquartile range(IQR) 0-5.57] versus 5.87[IQR, 3.54-6.71] Log10 IU/m L, respectively; P<0.001). Furthermore, co-infected patients were less likely to have detectable HCV RNA levels than HCV mono-infected patients(23.4% versus 56.5%, respectively; P<0.001). Those HBV-HCV co-infected patients had significantly lower median HBV DNA levels than those mono-infected with HBV(1.97[IQR, 1.3-3.43] versus 3.06[IQR, 2-4.28] Log10 IU/m L, respectively; P<0.001). The HBV-HCV co-infection group had higher ALT, AST, ALP, GGT, APRI and FIB-4 levels, but lower ALB and total platelet compared to the HBV mono-infection group, and similar to that of the HCV mono-infected group.In conclusion, These results suggest that co-infection with HCV and HBV inhibits the replication of both viruses. The serologic results of HBV-HCV co-infection in patients suggests more liver injury compared to HBV mono-infected patients, but is similar to HCV mono-infection. The second part:Hepatocellular carcinoma(HCC) is the third leading cause of death due to cancer worldwide with over 500,000 people affected annually. Although chemotherapy has been widely used to treat patients with HCC, alternate modalities to specifically deliver therapeutic cargos to cancer cells have been sought in recent years due to the severe side effects of chemotherapy. In this respect, aptamer-based tumor targeted drug delivery has emerged as a promising approach to increase the efficacy of chemotherapy and reduce or eliminate drug toxicity.We developed a new Hep G2-specific aptamer(HCA#3) by a procedure known as systematic evolution of ligands by exponential enrichment(SELEX) and exploited its role as a targeting ligand to deliver doxorubicin(Dox) to Hep G2 cells in vitro. Results are as follows in the second part:The selected 76-base nucleotide aptamer preferentially bound to Hep G2 hepatocellular carcinoma cells but not to control cells. The aptamer HCA#3 was modified with paired CG repeats at the 5￠-end to carry and deliver a high payload of intercalated Dox molecules at the CG sites. Four Dox molecules(mol/mol) were fully intercalated in each conjugate aptamer-Dox(Ap DC) molecule. Biostability analysis showed that the Ap DC molecules are stable in serum. Functional analysis showed that Ap DC specifically targeted and released Dox within Hep G2 cells but not in control cells, and treatment with HCA#3 Ap DC induced Hep G2 cell apoptosis but had minimal effect on control cells.In conclusion, These results suggest that our study demonstrated that HCA#3 Ap DC is a promising aptamer-targeted therapeutic that can specifically deliver and release a high doxorubicin payload in HCC cells. |
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