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Background Bromadiolone is the second-generation anticoagulant rodenticide widely used all over the world. Exposure to bromadiolone in early life stage can lead to neurodevelopmental toxicity, but its toxic mechanism of neurodevelopment is not clear so far. Objective To investigate the developmental neurotoxicity and mechanism of bromadiolone to zebrafish embryos. Methods Zebrafish embryos were randomly divided into four groups: a solvent control group (dimethylsulphoxide) and three bromadiolone exposure groups (0.39, 0.78, and 1.18 mg·L−1). The exposure period was from 4 h to 120 h post-fertilization. The number of spontaneous movement per minute was recorded at 24 h post-treatment. The locomotor ability of zebrafish larvae and the activity of acetylcholinesterase (AChE) were tested at 120 h post-treatment. The relative expression levels of neurodevelopment-related genes (elavl3, gap43, mbp, and syn2a) were measured by fluorescence quantitative PCR. Results Compared with the control group, the number of spontaneous movement per minute at 24 h decreased significantly in the 1.18 mg·L−1 bromadiolone exposure group (P<0.05). Compared with the control group, the total distance travelled of the zebrafish larvae in the 0.78 and 1.18 mg·L−1 bromadiolone exposure groups decreased by 60% and 69% respectively (P<0.05, P<0.01), and the total movement time decreased by 34% and 65% respectively (P<0.05, P<0.01). The AChE activity in the 1.18 mg·L−1 bromadiolone exposure group increased by 36% when compared with the control group (P<0.05). The fluorescence quantitative PCR results showed that compared with the control group, the expression levels of neurodevelopment-related genes elavl3, syn2a, and mbp were significantly down-regulated by 66%, 69%, and 65% in the 1.18 mg·L−1 bromadiolone exposure group respectively (P<0.01), the expression level of gap43 was up-regulated by 56% in the 0.78 mg·L−1 bromadiolone exposure group (P<0.01) and down-regulated by 34% in the 1.18 mg·L−1 bromadiolone exposure group (P<0.05). Conclusion Bromadiolone exposure could inhibit spontaneous movement and locomotive behavior, down-regulate the expression levels of neurodevelopment-related genes, hinder the release of neurotransmitters, and result in neurodevelopmental toxicity in the early-staged zebrafish.
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Aim To look for cold-protective drugs treating cryogenic freezing that may bring great damage to animal physiological system.Methods The protective effect of curcumin on frozen damage and the changes of thyroid function in mice were studied in this study.Quantitative analysis of the changes in survival time and metabolic indexes in mice disposed at(-20±1)℃ was conducted.Mouse serum free triiodothyronine(FT3) and free thyroxine(FT4) contents were detected by ELISA kit.HE staining was used to observe thyroid tissue morphological items.The expression of genes related to thyroid function was assessed via real-time quantitative PCR.Results The intraperitoneal injection of curcumin(12.5~50 mg·kg-1) could remarkably prolong the survival time of mice when exposed to cryogenic freezing.HE staining results displayed a recovered thyroid injury in morphology in the curcumin group, further with a notably improved metabolic indexes and evidently increase in serum FT3 and FT4 levels.The real-time quantitative PCR results indicated that the expressions of sodium iodide symporter(Nis), thyroglobulin(Tg) and thyroid peroxidase(Tpo) were up-regulated, and the expression of thyroid-stimulating hormone receptor(Tshr) was down-regulated.Sodium levothyroxine collabrated with the promoting thyroid effects of curcumin, while propylthiouracil inhibited the effects.Conclusion Curcumin can prolong the survival time of the cryogenic freezing mice, which is closely related to its ability to promote thyroid function.
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Objective:To explore the judging value of brain natriuretic peptide (BNP) on patient's condition of male patients with senile degenerated heart valvular disease (SDHVD) complicated heart failure (HF) .Methods :A total of 67 SDHVD + HF male patients were regarded as SHDVD group ,another 43 male HF patients ,who accepted treatment during the same period with corresponding age and without valvular heart disease ,were enrolled as pure HF group .Cardiac function indexes and plasma BNP level were measured and compared between two groups ,the correlation between BNP and left ventricular end -diastolic dimension (LVEDd) was analyzed ,and the cutoff point of BNP level for judging severity of SDHVD + HF was also calculated .Results:Compared with pure HF group , there were significant rise in LVEDd [ (49.79 ± 4.31) mm vs .(53.04 ± 7.10) mm] and plasma BNP level [ (214.43 ± 237.71) pg/ml vs . (682.06 ± 981.15 ) pg/ml ] , and significant reduction in left ventricular ejection fraction [LVEF ,(64.84 ± 5.83)% vs .(58.24 ± 7.99)% ] , P<0.05 or <0.01;percentage of moderate -severe heart dys‐function (NYHA class Ⅲ + Ⅳ) in SDHVD group was significantly higher than that of pure HF group (56.72% vs . 37.21% ) ,χ2 =3.988 , P=0.046. Spearman correlation analysis indicated that BNP level was positively correlated with LVEDd (r=0.588 ,P= 0.001) .The area under ROC (AUC) of BNP was 0.975 ,and the critical point of BNP level judging severity of male SDHVD complicated HF was 312 pg/ml ,and its sensitivity and specificity was 86.8% and 96.6% respectively .Conclusion:The SDHVD patient's condition is more severe compared with patients without valvular heart disease ,and BNP level is help to judging patient's condition .
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Objective: To investigate the effect and mechanism of rapamycin inhibiting mammalian target of RAPA (mTOR) on heart valve cell calciifcation in experimental rats. Methods: The rat’s valvular interstitial cells were isolated and the cells were cultured in 4 groups:①Normal control group,②Calciifcation group,③Rapamycin group and ④Calciifcation + rapamycin group. The apoptosis rates of valvular interstitial cells were detected by flow cytometry, calcium deposition was observed by Alizarin S staining, the calcified nodules were counted and the protein expressions of bmp-2, osteocalcin, osteopontin, smad-1 and caspase-3 were examined by Western blot analysis. Results: The rat's valvular interstitial cells were suceessfully isolated; the cell apoptosis rates were similar among different groups,P>0.05. The calciifed nodule in Calciifcation group (0.471 ± 0.091) was more than Normal control group (0.104 ± 0.023), while the nodule in Calciifcation + rapamycin group (0.237 ± 0.039) was less than Calciifcation group, allP0.05. Conclusion: Rapamycin may down-regulate the targeting protein expressions of bmp-2, osteopontin and smad-1 via inhibiting mTOR, therefore, reducing the valvular interstitial cell calcification which might be related to mTOR pathway suppression in experimental rats.