1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.
2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.
3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos. 相似文献
Summary We prospectively examined bone growth patterns in 894 children aged 6–17 years at the baseline visit, with a 6-year follow-up.
Results show bone “tracking” over a six-year interval and sexual dimorphism of bone attained levels and timing of peak bone
growth. Our findings underscore childhood and adolescence as critical periods for building bone and developing gender differences.
Introduction Bone growth patterns were prospectively examined in 894 Chinese children (496 males), aged 6–17 yrs, from a population-based
twin cohort. Whole-body bone area (BA), bone mineral content (BMC), and bone mineral density (BMD) were measured by DEXA at
baseline and a 6-yr follow-up.
Methods Graphic smoothing plots and generalized estimating equations were used to model bone attained levels, growth, and “tracking”.
Results Attained levels of BMC and BA increased curvilinearly with age. Male attained levels were higher than females after age ∼15 yr,
but BMD was lower between 13–17 yrs (Tanner stage I to IV). In both genders, peak BMC and BMD growth lagged ∼2 yrs behind
peak BA growth, which lagged 2 yrs behind peak height growth. Peak bone growth occurred 1–3 yrs later in males. Over the 6-yr
follow-up, all bone measurements “tracked”, but “shifting” across ranks also occurred, and baseline tertile ranking influenced
bone growth. Females with early menarche had higher attained levels than females with late menarche at age 12–13 yrs.
Conclusion Our findings confirm and expand previous studies on peak bone growth conducted in Caucasian cohorts, particularly sexually
dimorphic and maturational effects. The significant “tracking” of bone measurements in this 6-yr follow-up study underscores
the importance that osteoporosis prevention should begin in childhood and adolescence.
Fengxiu Ouyang and Binyan Wang contributed equally to this article.
Source(s) of support: This study is supported in part by grant R01 HD049059, R01 HL0864619 and R01 AR045651 from the National
Institute of Health and by the Food Allergy Project. 相似文献