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1.
Se Pu ; 41(3): 207-223, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-36861204

RESUMO

Ciwujia injection is commonly used to treat cerebrovascular and central nervous system diseases in clinical practice. It can significantly improve blood lipid levels and endothelial cell function in patients with acute cerebral infarction and promote the proliferation of neural stem cells in cerebral ischemic brain tissues. The injection has also been reported to have good curative effects on cerebrovascular diseases, such as hypertension and cerebral infarction. At present, the material basis of Ciwujia injection remains incompletely understood, and only two studies have reported dozens of components, which were determined using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS). Unfortunately, the lack of research on this injection restricts the in-depth study of its therapeutic mechanism.In the present study, a qualitative method based on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS) was developed to analyze the chemical components of Ciwujia injection. Separation was performed on a BEH Shield RP18 column (100 mm×2.1 mm, 1.7 µm) using 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phases, and gradient elution was performed as follows: 0-2 min, 0%B; 2-4 min, 0%B-5%B; 4-15 min, 5%B-20%B; 15-15.1 min, 20%B-90%B; 15.1-17 min, 90%B. The flow rate and column temperature were set to 0.4 mL/min and 30 ℃ respectively. MS1 and MS2 data were acquired in both positive- and negative-ion modes using a mass spectrometer equipped with an HESI source. For data post-processing, a self-built library including component names, molecular formulas, and chemical structures was established by collecting information on the isolated chemical compounds of Acanthopanax senticosus. The chemical components of the injection were identified by comparison with standard compounds or MS2 data in commercial databases or literature based on precise relative molecular mass and fragment ion information. The fragmentation patterns were also considered. For example, the MS2 data of 3-caffeoylquinic acid (chlorogenic acid), 4-caffeoylquinic acid (cryptochlorogenic acid), and 5-caffeoylquinic acid (neochlorogenic acid) were first analyzed. The results indicated that these compounds possessed similar fragmentation behaviors, yielding product ions at m/z 173 and m/z 179 simultaneously. However, the abundance of the product ion at m/z 173 was much higher in 4-caffeoylquinic acid than in 5-caffeoylquinic acid or 3-caffeoylquinic acid, and the fragment signal at m/z 179 was much stronger for 5-caffeoylquinic acid than for 3-caffeoylquinic acid. Four caffeoylquinic acids were identified using a combination of abundance information and retention times. MS2 data in commercial database and literature were also used to identify unknown constituents. For example, compound 88 was successfully identified as possessing a relative molecular mass and neutral losses similar to those of sinapaldehyde using the database, and compound 80 was identified as salvadoraside because its molecular and fragmentation behaviors were consistent with those reported in the literature. A total of 102 constituents, including 62 phenylpropanoids, 23 organic acids, 7 nucleosides, 1 iridoid, and 9 other compounds, were identified. The phenylpropanoids can be further classified as phenylpropionic acids, phenylpropanols, benzenepropanals, coumarins, and lignans. Among the detected compounds, 16 compounds were confirmed using reference compounds and 65 compounds were identified in Ciwujia injection for the first time. This study is the first to report the feasibility of using the UHPLC-Q/Orbitrap HRMS method to quickly and comprehensively analyze the chemical components of Ciwujia injection. The 27 newly discovered phenylpropanoids provide further material basis for the clinical treatment of neurological diseases and new research targets for the in-depth elucidation of the pharmacodynamic mechanism of Ciwujia injection and its related preparations.


Assuntos
Eleutherococcus , Humanos , Cromatografia Líquida de Alta Pressão , Ácido Clorogênico , Eletricidade Estática
2.
BMC Bioinformatics ; 23(1): 193, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610583

RESUMO

BACKGROUND: X chromosome inactivation (XCI) is an epigenetic phenomenon that one of two X chromosomes in females is transcriptionally silenced during early embryonic development. Skewed XCI has been reported to be associated with some X-linked diseases. There have been several methods measuring the degree of the skewness of XCI. However, these methods may still have several limitations. RESULTS: We propose a Bayesian method to obtain the point estimate and the credible interval of the degree of XCI skewing by incorporating its prior information of being between 0 and 2. We consider a normal prior and a uniform prior for it (respectively denoted by BN and BU). We also propose a penalized point estimate based on the penalized Fieller's method and derive the corresponding confidence interval. Simulation results demonstrate that the BN and BU methods can solve the problems of extreme point estimates, noninformative intervals, empty sets and discontinuous intervals. The BN method generally outperforms other methods with the lowest mean squared error in the point estimation, and well controls the coverage probability with the smallest median and the least variation of the interval width in the interval estimation. We apply all the methods to the Graves' disease data and the Minnesota Center for Twin and Family Research data, and find that SNP rs3827440 in the Graves' disease data may undergo skewed XCI towards the allele C. CONCLUSIONS: We recommend the BN method for measuring the degree of the skewness of XCI in practice. The R package BEXCIS is publicly available at https://github.com/Wen-YiYu/BEXCIS .


Assuntos
Doença de Graves , Inativação do Cromossomo X , Alelos , Teorema de Bayes , Cromossomos Humanos X/genética , Feminino , Genes Ligados ao Cromossomo X , Doença de Graves/genética , Humanos , Gravidez
3.
Front Genet ; 13: 831685, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559008

RESUMO

Behavioral disinhibition is one of the important characteristics of many mental diseases. It has been reported in literature that serious behavioral disinhibition will affect people's health and greatly reduce people's quality of life. Meanwhile, behavioral disinhibition can easily lead to illegal drug abuse and violent crimes, etc., which will bring great harm to the society. At present, large-scale genome-wide association analysis has identified many loci associated with behavioral disinhibition. However, these studies have not incorporated the parent-of-origin effects (POE) into analysis, which may ignore or underestimate the genetic effects of loci on behavioral disinhibition. Therefore, in this article, we analyzed the five phenotypes related to behavioral disinhibition in the Minnesota Center for Twin and Family Research data (nicotine, alcohol consumption, alcohol dependence, illicit drugs, and non-substance use related behavioral disinhibition), to further explore the POE of variants on behavioral disinhibition. We applied a linear mixed model to test for the POE at a genome-wide scale on five transformed phenotypes, and found nine SNPs with statistically significant POE at the significance level of 5 × 10-8. Among them, SNPs rs4141854, rs9394515, and rs4711553 have been reported to be associated with two neurological disorders (restless legs syndrome and Tourette's syndrome) which are related to behavioral disinhibition; SNPs rs12960235 and rs715351 have been found to be associated with head and neck squamous cell carcinoma, skin cancer and type I diabetes, while both SNPs have not been identified to be related to behavioral disinhibition in literature; SNPs rs704833, rs6837925, rs1863548, and rs11067062 are novel loci identified in this article, and their function annotations have not been reported in literature. Follow-up study in molecular genetics is needed to verify whether they are surely related to behavioral disinhibition.

4.
BMC Genom Data ; 22(1): 24, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215184

RESUMO

BACKGROUND: X chromosome inactivation (XCI) is that one of two chromosomes in mammalian females is silenced during early development of embryos. There has been a statistical measure for the degree of the skewness of XCI for qualitative traits. However, no method is available for such task at quantitative trait loci. RESULTS: In this article, we extend the existing statistical measure for the skewness of XCI for qualitative traits, and the likelihood ratio, Fieller's and delta methods for constructing the corresponding confidence intervals, and make them accommodate quantitative traits. The proposed measure is a ratio of two linear regression coefficients when association exists. Noting that XCI may cause variance heterogeneity of the traits across different genotypes in females, we obtain the point estimate and confidence intervals of the measure by incorporating such information. The hypothesis testing of the proposed methods is also investigated. We conduct extensive simulation studies to assess the performance of the proposed methods. Simulation results demonstrate that the median of the point estimates of the measure is very close to the pre-specified true value. The likelihood ratio and Fieller's methods control the size well, and have the similar test power and accurate coverage probability, which perform better than the delta method. So far, we are not aware of any association study for the X-chromosomal loci in the Minnesota Center for Twin and Family Research data. So, we apply our proposed methods to these data for their practical use and find that only the rs792959 locus, which is simultaneously associated with the illicit drug composite score and behavioral disinhibition composite score, may undergo XCI skewing. However, this needs to be confirmed by molecular genetics. CONCLUSIONS: We recommend the Fieller's method in practical use because it is a non-iterative procedure and has the similar performance to the likelihood ratio method.


Assuntos
Cromossomos Humanos X , Inativação do Cromossomo X , Animais , Feminino , Genótipo , Humanos , Fenótipo , Locos de Características Quantitativas , Inativação do Cromossomo X/genética
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