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Hepatitis B infection is a major global health problem and a primary cause of hepatocellular carcinoma (HCC). While various antiviral treatments have been explored, there is not yet a reliable method for preventing the progression of chronic hepatitis B infection into HCC. Hepatitis B virus X protein (HBx) plays a major role in viral replication, chronic inflammation and the pathogenicity of chronic liver disease. Modulation of purinergic receptors using their specific agonists has become a popular new strategy for modifying disease processes. In the present study, we investigated the involvement of the P2Y 11 receptor using its specific antagonist NF157 in some key aspects of HBx-induced liver disease in human MIHA hepatocytes, including mitochondrial dysfunction due to compromised mitochondrial membrane potential (MMP), oxidative stress resulting from overproduction of reactive oxygen species (ROS) and decreased antioxidant glutathione (GSH), production of proinflammatory cytokines and chemokines such as interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and chemokine (C-X-C motif) ligand 2 (CXCL2), as well as activation of cellular signaling pathways including the p38/mitogen-activated protein kinase (p38/MAPK) and nuclear factor-κB (NF-κB) pathways. Our findings present a novel new strategy for the treatment and prevention of chronic liver infection and subsequent morbidities induced by HBx via specific antagonism of the P2Y 11 purinergic receptor., Competing Interests: None.

The major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism has been implicated in susceptibility to cancer. However, the results are inconsistent. The aim of this meta-analysis is to evaluate the association between the MICA-TM polymorphisms and cancer risk. All eligible case-control studies published up to August 20, 2014 were identified by searching PubMed, Web of Science, CNKI and Wanfang databases. The cancer risk associated with the MICA polymorphism was estimated for each study by odds ratios (OR) together with its 95% confidence interval (CI), respectively. 21 studies from 19 publications with 3620 cases and 4903 controls were included. Overall, no significant associations between the MICA-TM polymorphism and cancer risk were found (A4 allele: OR = 0.97, 95% CI: 0.88-1.07; A5 allele: OR = 0.91, 95% CI: 0.81-1.04; A5.1 allele: OR = 1.03, 95% CI: 0.89-1.18; A6 allele: OR = 1.05, 95% CI: 0.95-1.15; A9 allele: OR = 0.96, 95% CI: 0.80-1.14; A10 allele: OR = 0.88, 95% CI: 0.43-1.79; del: OR = 2.50, 95% CI: 0.73-8.58; A7 allele: OR = 0.93, 95% CI: 0.43-2.00). When stratified by ethnicity, similar results were observed among Asians; however, there were significant association in Caucasian population for A5 (OR = 0.77, 95% CI: 0.68-0.87) and A9 allele (OR = 0.75, 95% CI: 0.66-0.85). This meta-analysis suggests that the MICA-TM A5 and A9 alleles may be an important protective factor for cancer in Caucasian populations.