Search

APOBEC3G (A3G) cytidine deaminase is an innate immune restriction factor that can edit and inhibit hepatitis B virus (HBV) replication. The preferred target of A3G is deamination of the third cytosine of 5′CCC to form a mutant marker 5′CC C → K. However, the distribution of A3G‐induced mutations on HBV DNA during infection is not well characterized. To provide clarity, we obtained the HBV DNA sequences from HBV infected individuals with and without hepatocellular carcinoma (HCC and non‐HCC, respectively), from the NCBI database, and calculated the r values of A3G‐induced 5′CC C → K mutation prevalence in HBV DNA. A3G‐induced mutations were weakly prevalent and mainly distributed in the plus strand of HBV DNA (r = 1.407). The mutations on the minus strand were weaker (r =.8189). There were A3G‐induced mutation regions in the 1200 to 2000 nt region of the plus strand and the 1600 to 1500 nt region of the minus strand. There was no significant difference in the r values of A3G‐induced mutations in HBV DNA between the HCC and non‐HCC groups. However, the rvalue of the plus strand 2400 to 2800 nt regions of HCC derived HBV DNA (r = 4.2) was significantly higher than that of the same regions of non‐HCC derived HBV DNA (r = 1.21). These findings clarify the weak prevalence and preferred plus‐strand distribution of A3G‐induced mutations on HBV DNA from HCC and non‐HCC. These findings may provide valuable clues regarding the interaction mechanism between A3G and HBV DNA and inform HCC screening. Highlights: A3G‐induced mutations were weakly prevalent and mainly distributed in the plus strand of HBV DNA. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) DNA is vulnerable to editing by human apolipoprotein B mRNA editing enzyme, catalytic polypeptide‐like (APOBEC) cytidine deaminases. However, the distribution of APOBEC‐induced mutations on HBV DNA is not well characterized. To this end, we obtained the HBV DNA sequence of HBV‐infected individuals with and without hepatocellular carcinoma (HCC and non‐HCC groups, respectively) from NCBI database and calculated the rapo values of APOBEC‐induced TpCpW→TpKpW mutation prevalence in HBV DNA. The results showed that the APOBEC‐induced mutations were mainly distributed in the minus strand of non‐HCC‐derived HBV DNA (rapo = 2.04), while the mutation on the plus‐strand was weaker (rapo = 0.99). There were high APOBEC‐induced mutation regions in the minus strand of HBV DNA 1 to 1000 nucleotides (nts) region and in the plus‐strand of HBV DNA 1000 to 1500 nts region; the mutations in the 1 to 1000 nts region were mainly TpCpW→TpTpW mutation types (total T/G: 111/18) and a number of these were missense mutations (missense/synonymous: 35/94 in P gene, 17/15 in S gene, and 5/10 in X gene). The difference between minus to plus‐strand rapo of HCC‐derived HBV DNA (1.96) was greater than that of the non‐HCC group (1.05). The minus‐strand rapo of HCC‐derived HBV DNA regions 1000 to1500nts and 1500 to 2000 nts (rapo = 4.2 and 4.2) was also higher than that of the same regions of non‐HCC‐derived HBV DNA (rapo = 1.2 and 1.1). Finally, the ratio of minus to plus‐strand rapo was used to distinguish HCC‐derived HBV DNA from non‐HCC‐derived HBV DNA. This study unraveled the distribution characteristics of APOBEC‐induced mutations on double strands of HBV DNA from HCC and non‐HCC samples. Our findings would help understand the mechanism of APOBECs on HBV DNA and may provide important insights for the screening of HCC. Highlight: There were high APOBEC‐induced TpCpW→TpKpW mutation regions in the minus strand of HBV DNA 1 to 1000 nucleotides (nts) region and in the plus‐strand of HBV DNA 1000 to 1500 nts region.The difference between minus to plus‐strand rapo of HCC‐derived HBV DNA was greater than that of the non‐HCC group. The results may help distinguish HCC‐derived HBV DNA from non‐HCC‐derived HBV DNA. [ABSTRACT FROM AUTHOR]

Objectives: This study is aimed to design and synthesize a prodrug of 5-aminosalicylic acid and evaluate its ameliorative effect on experimental ulcerative colitis (UC)., Materials and Methods: 5-Aminosalicylic acid-alanine (5-ASA-ALA) was synthesized and characterized. Its stability study was conducted in rat plasma and in the gastrointestinal tract environment, its transport characteristic was assessed using the Caco-2 cells. Its colon-targeting property was evaluated by the pharmacokinetic study, and incubation studies. A series of indicators were used to investigate its therapeutic effect on experimental colitis, including the survival rate and body weight of mice, the disease activity index (DAI), the colonic damage score and colon index, the myeloperoxidase (MPO) activity and the levels of malondialdehyde (MDA), total superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) in colonic tissues., Results: 5-ASA-ALA was barely absorbed in the Caco-2 monolayer or into the rat blood. It was remarkably stable when incubated in the upper gastrointestinal tract, while gradually hydrolyzed in the colon of rats. When orally administered to mice, 5-ASA-ALA had significantly greater therapeutic effect on colitis than the positive control., Conclusion: 5-ASA-ALA is demonstrated to be a promising oral colon-targeting prodrug of 5-ASA and has potential application in UC treatment.