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AIM: To explore the protective effect of astragalus glycyrrhiza decoction (AGD) on arsenic trioxide (ATO)-induced QT interval prolongation and its mechanism based on metabonomics. METHODS: The model of ATO-induced QT interval prolongation in rats was established, and ECG, blood routine, and metabonomics were detected, and the key targets were collected combined with network pharmacology. The possible candidate genes and pathways for the protective effect of AGD were screened by GO and KEGG enrichment analysis and then verified by experiments in vitro. RESULTS: AGD could significantly alleviate the ATO-induced QT interval of SD rats. GO enrichment analysis was mainly related to inflammatory response, reactive oxygen species, oxidative stress, inner cell vesicles, folds, inner cell vesicles, SMAD binding, R-SMAD binding, and signal receptor activator activity. KEGG analysis showed that it was mainly concentrated in the PI3K-Akt signal pathway, lipid and arteriosclerosis, FOXO signal pathway, TNF signal pathway, HIF-1, and other signal pathways. Through the H9c2 cell model in vitro, it was verified that AGD could reverse the expression of SIRT1 and FOXO1 proteins. CONCLUSION: AGD may improve the ATO-induced QT interval prolongation and reduce the cardiotoxicity of ATO by regulating the SIRT1 / FOXO1 signal pathway.
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Objective:To investigate the regulatory effect of miR-26a in radiation-induced heart disease (RIHD) mice.Methods:C57/BL6 mice were used to establish RIHD models. The cardiac function, fibrosis, the expression levels of collagen 1 (COL1) and connective tissue growth factor (CTGF), and miR-26a were detected in RIHD mice. Whether CTGF was the target gene of miR-26a was verified by dual luciferase kit. Moreover, cardiac fibroblasts were transfected with miR-26a up and miR-26a down lentivirus vectors to construct the miR-26a overexpression and underexpression cell models. The expression of CTGF, proliferation, and apoptosis of cardiac fibroblasts were detected.Results:In the RIHD mice, heart function was decreased, myocardial fibrosis was remodeled, the expression levels of COL1 and CTGF were up-regulated, and the expression level of miR-26a was down-regulated. Dual luciferase reporter assay confirmed that CTGF was the target gene regulated by miR-26a. Overexpression of miR-26a could inhibit the expression of CTGF, suppress the proliferation of cardiac fibroblasts, promote cell apoptosis and secrete collagen. Underexpression of miR-26a yielded the opposite results.Conclusion:MiR-26a affects the function of cardiac fibroblasts by targeting CTGF and probably mediates the process of radiation-induced myocardial fibrosis, which may become a new regulatory target of RIHD.
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Objective:To investigate the regulatory role of microRNA in radiation-induced heart disease (RIHD) in mice and provide a new strategy for its treatment.Methods:Based on the Gene Expression Omnibus database (GSE147241), which includes normal heart tissue and irradiation heart tissue, we conducted bioinformatics research and analysis to determine the differentially-expressed genes. Then, thirty male C57/BL6 mice were randomly divided into the control group, irradiation group and miR-133a overexpression intervention group. The heart received single dose of X-ray 20 Gy in the irradiation group and miR-133a overexpression intervention group, but not in the control group, and then fed for 16 weeks. Cardiac function was assessed by echocardiography. Myocardial fibrosis was detected by Masson staining. The expression levels of miR-133a, CTGF, COL-1 and COL-3 mRNA were detected by qRT-PCR. The expression levels of CTGF, COL-1 and COL-3 proteins were detected by western blot.Results:miR-133a was the differentially-expressed gene between the irradiation and control groups. Overexpression of miR-133a could mitigate the decrease in cardiac function and increase in myocardial collagen content ( P<0.01). Meantime, overexpression of miR-133a could down-regulate the expression levels of CTGF, COL-1, COL-3 mRNA and protein ( P<0.01). Conclusions:Radiation increases the synthesis of collagen and leads to myocardial fibrosis remodeling. Overexpression of miR-133a can alleviate the radiation-induced myocardial fibrosis.
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Objective:To establish the C57BL/6 mouse models of radiation-induced cardiopulmonary dysfunction.Methods:Twenty-four male C57BL/6 mice were randomly divided into the control and irradiation groups. Mice in the irradiation group were irradiated with 20 Gy electron beam and bred for 6 months after irradiation. Cardiac function was assessed using ultrasonography. The partial pressure of oxygen was detected by blood gas analysis. Cell apoptosis was observed by Tunel assay. Myocardial and pulmonary fibrosis was assessed by Masson staining.Results:The LVEF in the irradiation group was (68.60±10.92)%, significantly less compared with (81.75±8.79)% in the control group ( P< 0.01). The apoptotic index of heart in the irraiation group was (23.90±6.60)%, considerably higher than (3.25±3.38)% in the control group ( P< 0.01). The CVF of heart in the irradiation group was (15.42±5.72)%, significantly higher than (1.45±0.64)% in the control group ( P< 0.01). The PaO 2 level in the irradiation group was (86.10±7.60) mmHg, significantly lower compared with (107.16±9.01) mmHg in the control group ( P< 0.01). The apoptotic index of lung in the irradiation group was (27.90±8.94)%, significantly higher than (2.50±3.55)% in the control group ( P<0.01). The CVF of lung in the irradiation group was (17.76±5.77)%, remarkably higher than (2.50±3.55)% in the control group ( P< 0.01). Conclusion:Radiation can induce cardiopulmonary apotosis and fibrosis remodeling, which leads to cardiopulmonary dysfunction, suggesting the successful establishment of C57BL/6 mouse model of radiation-induced cardiopulmonary dysfunction.
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Objective:To evaluate the accuracy of parents ’ perception of whether their child is a picky eater and the specific food category the children avoideating according to the food frequency question-naire.Methods:This research selected 1 663 infants aged 4-36 months receiving non-diary complimen-tary food from maternal, infants, nutrition and growth study (MING Study) in 8 Chinese cities in which a combination of systematic cluster random sampling and purposive sampling was used .The general infor-mation, dietary status and picky eating status were collected through a self-designed questionnaire from the caregiver of the children .According to the parents ’ perception , the children were classified into picky/non-picky groups or avoid/non-avoid to a specific food category groups .Mann-Whitney U test was used to compare between the groups .Results: The reported percentage of picky eaters increased from 7.37%in 4-6 months old infants to 36.20%in 25-36 months old infants .Most picky infants in 4-6 months and 7-12 months old infants avoided eating dairy food ( 25% and 24%); while most picky toddlers aged 13-24 months and 25-36 months avoided eating vegetables (26.92% and 47.46%). The infants aged 4-6 months and 7-12 months who were perceived as picky by their parents took more kinds of food (8 and 19.5 kinds) than those who were not (6 and 18 kinds), while the picky toddlers aged 13-24 months and 25-36 months took fewer kinds of food (28.5 and 34 kinds for picky eaters, 31 and 37 kinds for non-picky eaters ) .The parents of infants aged 4-6 months judged correctly in every category of food without any statistical significance;the parents of 7-12 months old infants judged cor-rectly only in dairy food and eggs with statistical significance;those of 13-24 months old infants judged correctly in every food category except for vegetables with statistically significant difference in the category of eggs;those of 25-36 months old toddlers misjudged in dairy , beans and grains with no statistically significant difference in every category .Conclusion: Parents tend to misjudge their children ’ s picky eating behavior before the first 12 months of the child , and tend to make a more accurate perception after the 12th month.