Regulation of RNA Binding Protein Mbnl1 on Development of Mouse Embryonic Hematopoietic Stem Cells / 中国实验血液学杂志

OBJECTIVE@#To analyze the dynamic molecular expression characteristics of single cell RNA binding proteins (RBPs) in the development of mouse embryonic hematopoitic stem cells (HSCs), and obtain the functional research target RNA splicing factor--Mbnl1, to clarify the function of Mbnl1 involved in regulating mouse embryonic HSC development.@*METHODS@#Bioinformatics was used to analyze the single-cell transcriptome data of mouse embryos during HSC development, and the single-cell RBP dynamic molecular expression maps in HSC development was obtained. Mbnl1 was obtained by combining differential analysis and literature research screening. The Mbnl1-knockout mouse model was constructed by the CRISPER/Cas9 technology. Aorta-gonad-mesonephros (AGM) and yolk sac (YS) tissue in two genotype embryos of Mbnl1@*RESULTS@#The in vitro CFU-C experiment of hematopoietic cells preliminarily indicated that there was no significant difference in the number of cell colonies in AGM region and YS transformed by the two genotypes of Mbnl1@*CONCLUSION@#Through functional experiments in vivo and in vitro, it has been confirmed that knockout of the RNA splicing factor--Mbnl1 does not affect the development of HSPC in AGM region of mouse embryo.

Influence of CYP3A and MDR1 genetic polymorphisms on the pharmacokinetics of ciclosporin A / 国际药学研究杂志

Ciclosporin A (CsA). an immunosuppressive macrolide antibiotics, is widely applied to prevent rejections after organ transplants. CsA is mainly transported by P-glycoprotein (P-gp) and metabolized by cytochrome P450 (CYP450) 3A.Genetic polymorphisms of CYP3A and MDRl probably influence the expressions and bioactivity of CYP3A and P-gp.and may affect the pharmacokinetics of CsA.This issue summarizes the correlation between genetic polymorphisms of CYP3A and MDRl and the pharmacokinetics of CsA to guide the rational and individualized medication.

Association of nasopharyngeal carcinoma risk with cytochrome P450 CYP1A1 gene polymorphisms / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study.</p><p><b>METHODS</b>A total of 457 Cantonese nuclear families,consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943), were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma.</p><p><b>RESULTS</b>FBAT analysis showed that the minor allele frequencies (MAF) of the two SNP were 0.442 (C) and 0.339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification: chi2 = 2.399, P = 0.301; with stratification: low-titer group (VCA-IgA <1:80), MAF = 0.457 (C), chi2 = 1.221, P = 0.543; high-titer group (VCA-IgA > or = 1:80), MAF = 0.427 (C), chi2 =2.832, P = 0.243) . For m2 polymorphism, when VCA-IgA <1:80, the G allele showed decreased transmission under additive and dominant model (MAF = 0.347 (G); Zadditive = -2.120, Padditive = 0.034; Zdominant = - 2.303, Pdominant = 0.021) and a boundary P value was got with global statistic (chi2 = 5.394, P = 0.067) . Haplotype TG (0.057), constructed by m1 and m2, might decrease nasopharyngeal carcinoma risk (Z= -2.002, P=0.045). A boundary P value was also got with global statistic (chi2 =7.067, P=0.070).</p><p><b>CONCLUSION</b>There was no statistical significance between m1 polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.</p>