1.Effect of resveratrol on miRNA-106b in Alzheimer′s disease animal model
Danli KONG ; Zuguo ZHAO ; Yuqing HE ; Yuanlin DING ; Yanhong LUO ; Biyu LIANG ; Jin WANG ; Haibing YU
Chinese Journal of Neurology 2016;49(11):846-851
Objective To investigate the effect of resveratrol on miRNA-106b in Alzheimer′s disease ( AD ) animal model.Methods Fifty Kunming male mice were divided into five groups by completely randomized block sampling.The five groups included three dosage resveratrol groups , an AD model group and a control group.The AD models were established in one month prior to treatments. Subsequently, from the 31st day various doses of resveratrol were provided intragastricly for 60 days.Then the memory function was observed by the step-down test.Meanwhile, the varying expressions of APP , P62, ApoA1, miRNA-106b, ABCA1 were tested in each group to determine whether there is the binding site for miRNA-106b in APP 3′UTR sequence.Results Compared with the control group by step-down test, the memory function of the AD model group mice decreased in different degree , which in the drug treatment group was higher than that in the model group (P<0.05).Compared with the AD group, the expression of APP (1.131 ±0.035) in the drug treatment group was higher than that in the model group (0.652 ± 0.026), while the P62 (0.412 ±0.022) and ApoA1 (0.534 ±0.032) were lower than the model group ( all P<0.05 ).High and medium dose groups of resveratrol treatment reduced varying degrees of APP (0.733 ±0.018,0.929 ±0.019,F=177.733) levels, and increased P62(0.954 ±0.035,0.633 ±0.015, F=434.5 ) and ApoA1 ( 1.042 ±0.051, 0.824 ±0.034, F=286.582 ) levels ( all P<0.05 ).The expression of miRNA-106b (0.464 ±0.313) and ABCA1(0.293 ±0.042) in the model group was lower than that in the control group (miRNA-106b 1.064 ±0.032, F=238.159; ABCA1 0.781 ±0.027,F=341.61;both P<0.05).The miRNA-106b (0.843 ±0.034, 0.601 ±0.012) and ABCA1 (0.882 ± 0.025, 0.624 ±0.036) levels in the high, medium dose resveratrol treatment groups increased to different extent ( both P<0.05 ).After the drug treatment , luciferase reporter vector experiments showed that the APP 3′UTR sequence contains the binding site of miRNA-106b.Conclusions APP is one of the target genes of miRNA-106b.Resveratrol is capable of improving AD by enhancing the expression of miRNA-106b and down-regulating the target genes including APP , P62 and ApoA1.This provides a new theoretical basis for the clinical treatment of AD.
2.Association between antioxidant nutrients and pregnancy complications: a Mendelian randomization study
WANG Shuang ; TAN Xiwei ; LING Yao ; HUANG Ruixian ; MA Yong ; KONG Danli ; DING Yuanlin
Journal of Preventive Medicine 2024;36(4):345-349
Objective:
To investigate the causal relationship between antioxidant nutrients and pregnancy complications, so as to provide the reference for the prevention and treatment of pregnancy complications.
Methods:
Data of seven antioxidant nutrients including vitamin A, vitamin C, vitamin E, selenium, zinc, copper and iron were collected from genome-wide association study (GWAS) Catalog database, and data of four pregnancy complications including gestational diabetes mellitus, pre-eclampsia, spontaneous abortion and preterm birth were collected from the Finland database. Single nucleotide polymorphism (SNP) data were collected, and 27 SNPS strongly correlated with seven antioxidant nutrients were selected as instrumental variables. Mendelian randomization (MR) analyses were performed using the inverse-variance weighted (IVW) method with seven antioxidant nutrients as exposures factors and four pregnancy complications as outcome variables. The heterogeneity was assessed using the Cochran's Q test, the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression, and the robustness of the results was verified with the leave-one-out.
Results:
Cochran's Q test showed heterogeneity of MR results between vitamin C and gestational diabetes mellitus, preeclampsia and preterm birth, between vitamin E and iron and gestational diabetes (all P<0.05), and a random effect model was employed. There was no heterogeneity in other results (all P>0.05), and a fixed effect model was employed. MR analysis results showed that there was no causal association between seven antioxidant nutrients and the risk of four pregnancy complications (all P>0.05). MR-PRESSO test and the MR-Egger regression identified no horizontal pleiotropy of instrumental variables (both P>0.05).
Conclusion
This study did not find genetically predicted associations of antioxidant nutrients with pregnancy complications.