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Objective To explore the association between the sortilin-related receptor,L (DLR class) A repeats containing (SORL1) gene single nucleotide polymorphisms (SNPs) and sporadic Alzheimer's disease (SAD) in Han Chinese populations.Methods Five candicate SNPs,including rs985421,rs12364988,rs4598682,rs3781834,and rs3781836,within the SORL1 gene were genotyped by LDR-PCR methods,and the association of these SNPs with SAD risk were also analyzed in a case-control study with 179 SAD and 106 healthy controls.Results The results indicated that the A allele frequency of the SORL1 SNP rs985421 was significant difference between SAD and healthy controls (Trend test:P =0.0044,P adj =0.022; Allelic:P=0.0023,P adj =0.012).In subjects without APOE s4 allele,higher frequency of the A allele of rs985421 was observed in SAD patients compared with control subjects by the stratified analysis (OR=2.260,95％ CI =1.269-4.024,P=0.0048).In addition,logistic regression analysis further revealed that the A allele of SORL1 SNP rs985421 was significantly associated with SAD risk (OR=1.968,95％ CI =1.273-3.042,P=0.002).However,no positive signals in other four SNPs within the SORL1 gene were observed (all P＞ 0.05).Conclusions The A allele of SORL1 SNP rs985421 may be an APOE ε4-independent factor associated with SAD risk.
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ObjectiveTo explore the effects of fisetin on the learning and memory abilities impairments induced by Aβ in mice.MethodsAlzheimer's disease (AD) animal model was made by single intracerebroventricular infusion of Aβ (1-42) through guide cannula.Fisetin was orally administered 7 days before Aβ infusion once a day,and continued throughout the experimental period.Water maze test began on day 3 after Aβ infusion.All mice were sacrificed and hippocampi were dissected immediately after behavioral test.The protein expression of hippocampal nuclear Nrf2 and the mRNA level of HO-1,GCLC and GCLM were examined by western blotting and RT-RCR techniques respectively.Results ( 1 ) Aβ (1-42) significantly increased escape latency in hidden platform test ( (25.4 ± 3.33 ) s ),and decreased the number of crossings in probe test ( 1.70 ± 0.25 ) compared with control ((9.05 ± 1.37 )s) for hidden plat form ;4.50 ± 0.41 for probe test) and Aβ (42-1)-treated group ( ( 10.80 ± 1.38)s) for hidden platform test; 4.10 ±0.39 for probe test; P＜0.01 ).The prolonged treatment with fisetin dose-dependently reversed the changes (10 mg/kg:17.54 ± 3.56s for hidden platform test;2.50 ± 0.40 for probe test,P＜0.05,20 mg/kg:( 13.04 ± 2.36) s for hidden platform test;3.60 ±0.36 for probe test,P＜0.01 ).(2) Aβ (1-42) significantly decreased the nuclear Nrf2 protein level (0.07 ±0.02),and mRNA level (0.45 ±0.04) of HO-1,GCLC (0.41 ± 0.04) and GCLM (0.26 ± 0.03 ) in the hippocampus of mice compared with control (0.18 ± 0.02 for Nrf2 ;0.83 ± 0.09 for HO-1 ; 1.01 ± 0.10 for GCLC; 0.65 ± 0.07 for GCLM) and Aβ (42-1 ) -treated group (0.21 ± 0.02 for Nrf2 ; 0.90 ± 0.08 for HO-1 ; 1.11 ± 0.11 for GCLC ; 0.72 ± 0.07 for GCLM) ( P ＜ 0.05 or P ＜ 0.01 ).However,fisetin administration significantly counteracted these changes ( 10 mg/kg:0.11± 0.01 for Nrf2 ; 0.56 ± 0.06 for HO-1 ; 0.61 ± 0.04 for GCLC ; 0.35 ± 0.04 for GCLM ; 20 mg/kg:0.16 ± 0.02for Nrf2;0.79±0.10 for HO-1;0.86±0.09 for GCLC;0.51±0.04 for GCLM;P＜0.05).ConclusionFisetin attenuates learning and memory impairments induced by Aβ (1-42) through activation of Nrf2 antioxidant signaling pathway.
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Objective To observe colorectal tumor's growth in hyperglycemia mice and its vascular endothelial growth factor (VEGF)'s expression, insulin-like growth factor-1 (IGF-1)'s variation of blood through the experiment, then to ascertain whether type 2 diabetes mellitus (T2DM) danger factors to promote colorectal cancer happen and progress or not. Methods The mouse model of colorectal cancer combined T2DM was established. The volume of tumor was observed. After 5 weeks, all mice were executed and IGF-1 in the blood and the expression of VEGF in the tumor tissue was examined. Results The average tumor volume of colorectal tumor-diabetes group [(1628.5±882) mm3] were larger than that of colorectal tumor group [(1950.2±726) mm3] (P <0.05), and its expression IGF-1 of blood [(105.33±32.32) ng/ml] were higher than that of the control group [(69.83±25.57) ng/ml] and colorectal tumor group [(70.17±25.27) ng/ml] (P <0.05). The expression of VEGF [(70.0±11.5)%] in colorectal tumor-diabetes group were significantly higher than that of colorectal tumor group [(42.9±7.5)%] (P <0.05), too. Conclusion The model of T2DM and transplanted colorectal tumor can be duplicated successfully in ICR mice. Diabetes mellitus may be one reason of promoting colorectal cancer progress. Besides high blood glucose, its mechanism is the high level of IGF-1 which can inhibit apoptosis, promote cell differentiation and hyperplasia, and through inducing VEGF duplicating, heighten its expression, promote the tumor vessel growth, lead to tumor happen and metastasis.