Interaction of major genes predisposing to hepatocellular carcinoma with genes encoding signal transduction pathways influences tumor phenotype and prognosis

Studies on rodents and humans demonstrate an inherited predisposition to hepatocellular carcinoma （HCC）. Analysis of the molecular alterations involved in the acquisition of a phenotype resistant or susceptible to hepatocarcinogenesis showed a deregulation of G1 and S phases in HCC of genetically susceptible F344 rats and a G1-S block in lesions of resistant Brown norway （BN） rats. Unrestrained extracellular signal-regulated kinase （ERK） activity linked to proteasomal degradation of dual-specificity phosphatase 1 （DUSP1）, a specific ERK inhibitor, by the CKS1-SKP2 ubiquitin ligase complex occurs in more aggressive HCC of F344 rats and humans. This mechanism is less active in HCC of BN rats and human HCC with better prognosis. Upregulation of iNos cross-talk with IKK/NF-KB and RAS/ERK pathways occurs in rodent liver lesions at higher levels in the most aggressive models represented by HCC of F344 rats and c-Myc-TGF-α transgenic mice. iNOS, IKK/NF-κB, and RAS/ERK upregulation is highest in human HCC with a poorer prognosis and positively correlates with tumor proliferation, genomic instability and microvascularization, and negatively with apoptosis. Thus, cell cycle regulation and the activity of signal transduction pathways seem to be modulated by HCC modifier genes, and differences in their efficiency influence the susceptibility to hepatocarcinogenesis and probably the prognosis of human HCC.

Impact of global change on transmission of human infectious diseases

Global change,which refers to large-scale changes in the earth system and human society,has been changing the outbreak and transmission mode of many infectious diseases.Climate change affects infectious diseases directly and indirectly.Meteorological factors including temperature,precipitation,humidity and radiation influence infectious disease by modulating pathogen,host and transmission pathways.Meteorological disasters such as droughts and floods directly impact the outbreak and transmission of infectious diseases.Climate change indirectly impacts infectious diseases by altering the ecological system,including its underlying surface and vegetation distribution.In addition,anthropogenic activities are a driving force for climate change and an indirect forcing of infectious disease transmission.International travel and rural-urban migration are a root cause of infectious disease transmission.Rapid urbanization along with poor infrastructure and high disease risk in the rural-urban fringe has been changing the pattern of disease outbreaks and mortality.Land use changes,such as agricultural expansion and deforestation,have already changed the transmission of infectious disease.Accelerated air,road and rail transportation development may not only increase the transmission speed of outbreaks,but also enlarge the scope of transmission area.In addition,more frequent trade and other economic activities will also increase the potential risks of disease outbreaks and facilitate the spread of infectious diseases.