ABSTRACT
Congenital Zika syndrome (CZS) is a cluster of malformation, and the mechanisms that lead it are still unclear. Using hypothesis-driven candidate genes and their function in viral infections, single-nucleotide polymorphisms (SNPs) were genotyped by quantitative polymerase chain reaction in a sample population from Sergipe State, Brazil. This study shows that rs3775291 SNP at Toll-like receptor 3, which triggers type I interferon antiviral responses in mothers infected by Zika virus during pregnancy, is associated with CZS occurrence (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.158-4.148). Moreover, rs1799964 SNP at tumor necrosis factor-α gene in CZS babies is associated with severe microcephaly (OR, 2.63; 95% CI, 1.13-6.21).
Subject(s)
Genotype , Microcephaly/genetics , Toll-Like Receptor 3/genetics , Tumor Necrosis Factor-alpha/genetics , Zika Virus Infection/complications , Zika Virus Infection/genetics , Adolescent , Adult , Brazil , Female , Genotyping Techniques , Humans , Infant, Newborn , Male , Middle Aged , Polymorphism, Single Nucleotide , Real-Time Polymerase Chain Reaction , Young AdultABSTRACT
We investigated the effect of oral administration of hydroalcoholic extract of Brazilian red propolis (HERP) on DMBA-induced oral squamous cell carcinomas (OSCC) in rodents. The chemical components of the HERP were assessed by high-performance liquid chromatography (HPLC). Carcinogenesis was topically induced in the lower lip of 25 rats using 9,10-dimethyl-1,2-benzanthracene (DMBA); the tumour was treated with saline (TUM1) and Tween 80 (TUM2) as well as HERP at 10, 50 and 100 mg/kg (HERP10, HERP50 and HERP100, respectively) for 20 weeks. Topical application of saline and oral administration of 100 mg/kg HERP was used in five rats as a control group (CTR). After 26 weeks, the histological malignancy grading and immunohistochemical expression of Ki-67 and p16(INK4A) were assessed in the tumours/tissue samples. The compounds identified were propyl gallate, daidzein, catechin, epicatechin, formononetin and biochanin A. Formononetin, daidzein and biochanin A showed concentration of 23.29, 0.38 and 0.67 mg/g of HERP, respectively. HERP at doses of 50 and 100 mg/kg inhibited 40% of OSCC growth and promoted a 3-week delay in development of clinically detectable tumours. Epithelial dysplasia was observed in all samples with no clinical tumour, except in CTR. No significant difference in the immunoexpression of Ki-67 and p16(INK4A) was observed between HERP-treated and saline/Tween 80-treated groups (p > 0.05). Our results suggest that HERP exerts chemopreventive activity on the progression of DMBA-induced epithelial dysplasia to OSCC in an experimental model of labial carcinogenesis; however, this effect is not associated with Ki-67 and p16(INK4A) immunoexpression.
