Design, Synthesis, And Evaluation Of Cyanopyridines As Anti-Colorectal Cancer Agents Via Inhibiting STAT3 Pathway.

BACKGROUND: Colorectal cancer is one of the common malignant tumors. Cyanopyridine and aminocyanopyridine having a carbon-nitrogen bond have been shown to have significant anticancer effects. STAT3 is a promising therapeutic target in multiple cancers. However, there are currently no effective STAT3 inhibitors in clinical practice for the treatment of colorectal cancer. MATERIALS AND METHODS: We screened 27 cyanopyridines for their anticancer activity by cell viability. The HCT-116, RKO, and DLD-1 cell lines were used to evaluate the anti-colorectal cancer effect of 3n. Scratch experiments and colony formation assays were used for the assessment of cell migration and proliferation capacity. Phosphorylated STAT3, STAT3, MCL-1, and Survivin levels were assessed by Western blot analysis. RESULTS: In this study, we synthesized 27 cyanopyridines and screened their anticancer activities in three human tumor cells, HCT-116, Hela229, and A375. We found that 2-amino-3-cyanopyridine 3n has better anticancer activity with IC50 values in the low micromolar range. Furthermore, 3n significantly inhibited the migration and colony formation of colorectal cancer cells. Mechanistically, 3n inhibited the expression of STAT3 phosphorylation in a dose- and time-dependent manner. CONCLUSION: 3n is worth of further investigations toward the discovery of STAT3 inhibitor as a drug candidate for cancer therapy.

Prevalence of hepatitis B virus, hepatitis C virus, human immunodeficiency virus and Treponema pallidum infections in hospitalized patients before transfusion in Xiangya hospital Central South University, China from 2011 to 2016.

BACKGROUND: Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and Treponema pallidum (TP) infections are considered classic transfusion-transmissible infections (TTIs). Few data are available about the prevalence of TTIs in patients before blood transfusion in China. This study aimed to investigate the seroprevalence of four TTIs among patients before blood transfusion in Xiangya Hospital Central South University, China. METHODS: From 2011 to 2016, 442,121 hospitalized patients before possible blood transfusion were tested for hepatitis B surface antigen (HBsAg), anti-HCV, syphilis antibody (anti-TP) and anti-HIV. RESULTS: Of the 442,121 patients, the overall positivity of the four TTI serum markers was 15.35%. The positive rates of HBsAg, anti-HCV, anti-HIV and anti-TP were 10.98, 1.43, 0.16 and 2.78%, respectively. TTI serum markers showed a significant difference by gender, with positive rates of 17.98% for males and 12.79% for females. The prevalence of TTI serum markers varied significantly by age. The overall co-infection rate was 0.63%, and the top three multiple infections were HBV-TP, HBV-HCV, and HCV-TP. The co-infection rates of HBV-TP and HBV-HCV showed a significant decrease from 2011 to 2016, while the rates of other co-infections remained stable. CONCLUSIONS: The prevalence of TTIs in patients before blood transfusion is much higher compared to that in blood donors in the region. The infection rates of HIV and TP increased, and the infection rate of HBsAg decreased in recent years.