Prescription of Sageretia hamosa Brongn Relieved Goiter through Promoted Apoptosis of Thyroid Cells via miR-511-3p and PTEN/PI3K/Akt Pathway.

Goiter is thyroid enlargement, in China, Sageretia hamosa Brongn (SHB) can be used to treat goiter, but it has not been reported. Therefore, data analytics of SHB prescription on thyroid were explored in this study to provide a theoretical support for SHB in the treatment of goiter. In this study, rat in goiter model was constructed by using propylthiouracil (PTU) and treated with SHB prescription. Thyroid function about the triiodothyronine (T3), free thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured by ELISA; thyroid coefficient was calculated after weighed thyroid; and HE staining was applied to assess the morphology of thyroid tissue. miRNA microarrays were employed to detect miRNA expression in thyroid tissue of rats. Expression of miR-511-3p was measured by RT-qPCR; expression of proteins (PTEN and apoptosis-related proteins) was tested by western blotting; relationship between miR-511-3p and PTEN was investigated by dual luciferase reporter gene assay; cell viability rate was determined by CCK-8; and cell cycle distribution and apoptosis rate were detected by flow cytometry. The results showed that SHB prescription ameliorated goiter and downregulated miR-511-3p. miR-511-3p targeted PTEN in thyroid cells and PTEN negatively regulated the activation of PI3K/Akt pathway. Furthermore, the inhibition of apoptosis in thyroid cells caused by the overexpression of miR-511-3p or the activation of PI3K/Akt pathway was reversed by treatment of SHB prescription, inhibition of miR-511-3p, or overexpression of PTEN. In conclusion, SHB prescription promoted apoptosis of thyroid through decreased miR-511-3p and regulated PTEN/PI3K/Akt pathway, it might suggest possible medical applications.

Mutation-sensitive molecular switch method to detect CES1A2 mutation in the Chinese Han and Yao populations.

Carboxylesterase 1 (CES1) is involved in the metabolic activation of a variety of prodrugs into active derivatives and plays an important role in pharmacokinetics and pharmacodynamics. A single-nucleotide polymorphism, A(-816)C, of the CES1A2 gene has been shown to enhance transcription efficiency and increase enzyme activity. The aim of this study was to develop an easy method to detect this polymorphism. For this we used the mutation-sensitive molecular switch method to investigate the polymorphism distribution in the Chinese Han and Yao populations. The method was well validated by direct sequencing. In 204 Han individuals, the percentages of the distribution of CES1A2 A(-816)C genotypes are AA 58.33% (n=119), AC 35.78% (n=73), and CC 5.88% (n=12). The genotype frequencies are AA 47.76% (n=96), AC 42.79% (n=86), and CC 9.45% (n=19) in 201 Yaos. The frequency of the mutant C allele in the Yao population is significantly higher than that in the Han population (30.85% vs. 23.77%, p=0.0239). The method can be easily used for the detection of the single-nucleotide polymorphism in CES1A2, and we found that there is a marked difference in mutant C allele between Chinese Han and Yao populations, suggesting individual and ethnic differences of CES1 drug metabolism between these two populations.