Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer in the world. To comprehensively investigate the utility of microRNAs (miRNAs) and protein-encoding transcripts (messenger RNAs [mRNAs]) in HCC as potential biomarkers for early detection and diagnosis, we exhaustively mined genomic data from three available omics datasets (GEO, Oncomine, and TCGA), analyzed the overlaps among gene expression studies from 920 hepatocellular carcinoma samples and 508 healthy (or adjacent normal) liver tissue samples available from six laboratories, and identified 178 differentially expressed genes (DEGs) associated with HCC. Paired with miRNA and lncRNA data, we identified 23 core genes that were targeted by nine differentially expressed miRNAs and 21 HCC-specific lncRNAs. We further demonstrated that alterations in these 23 genes were quite frequent, with five genes altered in over 5% of the population. Patients with high levels of YWHAZ, ENAH, and HMGN4 tended to have high-grade tumors and shorter overall survival, suggesting that these genes could be promising candidate biomarkers for disease and poor prognosis in patients with HCC. Our comprehensive mRNA, miRNA, and lncRNA omics analyses from multiple independent datasets identified robust molecules that may be used as biomarkers for early HCC detection and diagnosis.

Rationale: Ascorbate is an essential micronutrient known for redox functions at normal physiologic concentrations. In recent decades, pharmacological ascorbate has been found to selectively kill tumour cells. However, the dosing frequency of pharmacologic ascorbate in humans has not yet been defined.Methods: We determined that among five hepatic cell lines, Huh-7 cells were the most sensitive to ascorbate. The effects of high-dose ascorbate on hepatoma were therefore assessed using Huh-7 cells and xenograft tumour mouse model.Results: In Huh-7 cells, ascorbate induced a significant increase in the percentage of cells in the G0/G1 phase, apoptosis and intracellular levels of ROS. High doses of ascorbate (4.0 pmol cell-1), but not low doses of ascorbate (1.0 pmol cell-1), also served as a pro-drug that killed hepatoma cells by altering mitochondrial respiration. Furthermore, in a Huh-7 cell xenograft tumour mouse model, intraperitoneal injection of ascorbate (4.0 g/kg/3 days) but not a lower dose of ascorbate (2.0 g/kg/3 days) significantly inhibited tumour growth. Gene array analysis of HCC tumour tissue from xenograft mice given IP ascorbate (4.0 g/kg/3 days) identified changes in the transcript levels of 192 genes/ncRNAs involved in insulin receptor signalling, metabolism and mitochondrial respiration. Consistent with the array data, gene expression levels of AGER, DGKK, ASB2, TCP10L2, Lnc-ALCAM-3, and Lnc-TGFBR2-1 were increased 2.05-11.35 fold in HCC tumour tissue samples from mice treated with high-dose ascorbate, and IHC staining analysis also verified that AGER/RAGE and DGKK proteins were up-regulated, which implied that AGER/RAGE and DGKK activation might be related to oxidative stress, leading to hepatoma cell death.Conclusions: Our studies identified multiple mechanisms are responsible for the anti-tumour activity of ascorbate and suggest high doses of ascorbate with less frequency will act as a novel therapeutic agent for liver cancer in vivo.

The plant Coleus forskohlii is distributed primarily in India, Thailand, China, Egypt and Brazil and has a history of use in the treatment of multiple diseases. Isoforskolin (ISOF) is the principle active component of C. forskohlii native to China and has previously been studied for its biological effects. The aim of the present study was to evaluate the effect of ISOF on the proinflammatory responses induced by recombinant Borrelia burgdorferi basic membrane protein A (rBmpA). In in vitro experiments, the proinflammatory effects of rBmpA and the anti-inflammatory function of ISOF were evaluated in murine macrophages, human macrophages and dendritic cells by detecting the transcription and expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6. In in vivo experiments, mean arthritis index and X-ray and histopathological examinations were used to verify the role of ISOF in experimental Lyme arthritis in mice. The results indicated that rBmpA, which induced the transcription and expression of TNF-α and IL-6, activated proinflammatory responses in murine macrophages, human macrophages and dendritic cells. In turn, ISOF downregulated the transcription and expression of TNF-α and IL-6 induced by rBmpA. Additionally, the in vivo experiments demonstrated that ISOF could also inhibit the symptoms of experimental Lyme arthritis. These results suggest that ISOF may have a potential application as an anti-inflammatory agent for the treatment of Lyme arthritis.

This study was to investigate the relationship between IL-18-137G/C polymorphism and TB risk by meta-analysis. The literatures about the IL-18-137G/C polymorphism and risk of tuberculosis were selected from four English databases and four Chinese databases. Data were extracted from the studies by two independent reviewers. Statistical analysis was executed using Revman 5.3 and Stata 11.0 software. A total of 5 studies with 558 TB patient and 720 controls were included in this meta-analysis, The results showed that-137G/C polymorphisms in the IL-18 gene were associated with TB risk in china when taking comparisons of the G allele vs. C allele (OR=1.49, 95% CI=1.21-1.84, P=0.0002), GG vs. GC+X.06, P=0.0003). It was also significant in the subgroup analysis of Chinese adults (G allele vs. C allele: OR=1.32, 95%=CI 1.03-1.70, P=0.003; GG vs. GC+CC: OR=1.39, 95% CI=1.01-1.91, P=0.04) and Chinese children (G allele vs. C allele: OR=1.91, 95% CI=1.31-2.78, P=0.0008; GG vs. GC+CC: OR=2.02, 95% CI=1.33-3.07, P=0.0010). This study provides the evidence that the allele G of IL-18-137G/C polymorphism was closely associated with TB risk in China.