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Diabetes mellitus (DM) has been regarded as an important risk factor for Alzheimer's disease (AD), and diabetic patients and animals have shown cognitive dysfunction. More research has shown that the amyloid-β (Aβ), which is a hallmark of AD, was found deposited in the hippocampus of diabetic rats. This Aβ accumulation is regulated by the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein (LRP-1). However, the expression of RAGE and LRP-1 in diabetic rats is not very clear. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether the expression of RAGE and LRP-1 is related to Aβ deposition at the hippocampus, prefrontal lobe, and amygdala in DM. We found that diabetic rats had longer escape latency and less frequency of entrance into the target zone than that of the control group (P < 0.05) in the Morris water maze (MWM) test. The Aβ expression in the hippocampus and prefrontal lobe significantly increased in the DM group compared to the control group (P < 0.05). RAGE increased (P < 0.05), while LRP-1 decreased (P < 0.05) in the hippocampus tissue and prefrontal lobe tissue of DM rats. The Aβ deposition was correlated with RAGE positively (P < 0.05), but with LRP-1 negatively (P < 0.05). Further, the expression levels of Aβ, RAGE, and LRP-1 were not changed in the amygdala between the diabetic rats and the control group. These findings indicated that upregulating RAGE and/or downregulating LRP-1 at the hippocampus and the prefrontal lobe contributed to the Aβ accumulation and then further promoted the cognitive impairment of diabetic rats.

Vitamin D receptor (VDR) Cdx-2 polymorphism (rs11568820) has been indicated to be associated to cancer susceptibility. However, published studies reported mixed results. This meta-analysis was conducted to get a more accurate estimation of the association between Cdx-2 polymorphism and cancer risk.We identified 25 independent studies with a total of 34,018 subjects published prior to March 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to cancer. Separate analyses were conducted on features of the population such as ethnicity, source of controls, and cancer types.Meta-analysis results showed that Cdx-2 polymorphism significantly increased cancer risk in the homozygous model in overall analysis. According to the further stratified analysis, significant association was found between Cdx-2 variant and cancer risk in American-Africans in the homozygous, recessive, and dominant comparison models. However, no significant associations were found in Caucasians and Asians. When stratified by different cancer types, significant association was observed between Cdx-2 variant and an increased risk of colorectal cancer in the homozygous, recessive, and dominant models. In addition, ovarian cancer susceptibility increased based on the homozygous and dominant comparison models.Our study indicated that VDR Cdx-2 polymorphism was associated with an increased cancer risk, particularly in American-Africans, colorectal, and ovarian cancers. However, other factors may impact on the association. Further multicenter studies are needed to confirm the effects of Cdx-2 polymorphism on cancer susceptibility.

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Introduction: The relationship between obesity and cognitive impairment (CI) is highly heterogeneous in previous studies, which may be due to insufficient consideration of anthropometric indicators and sex. This study compared the cross-sectional relationships among body mass index (BMI), waist-to-hip ratio (WHR) and CI among people aged ≥40 years, and sex-specific relationships were also considered. Methods: This was a population-based cross-sectional study with a cluster sampling design. CI was defined as a Mini-Mental State Examination score lower than the cutoff value. Multivariate logistic regression was used. BMI and WHR were fitted as both restricted cubic splines and categorical data. Stratified analysis and interaction analysis were performed to explore the sex-specific relationship. Results: A total of 1792 subjects (40.5% male) were analyzed, and 230 were confirmed to have CI. The relationships among BMI, WHR and CI were significant (Poverall=0.023, Pnonlinear=0.097; Poverall=0.017, Pnonlinear=0.078, respectively) but exhibited an opposite trend in the total population in the analyses with BMI and WHR as restricted cubic splines. Further categorical analyses showed that subjects with a BMI <23 kg/m2 tended to have a higher risk of CI than those with BMI ≥23 kg/m2(16.2% vs. 11.8%, P=0.017; OR = 1.366 [0.969–1.926], P = 0.075), and subjects with a WHR >0.92 had a significantly higher risk of CI than those with a WHR ≤0.92 (11.7% vs. 16.2%, P=0.011; OR = 1.619 [1.161–2.258], P = 0.005). In addition, the relationship between a low BMI and CI was more significant in males (P = 0.034), while the relationship between a high WHR and CI was more significant in females (P = 0.002). Further studies is needed to confirm the sex differences because of the marginal significance result in the interaction analysis (P = 0.051 for interaction term BMI×sex; P = 0.056 for interaction term WHR×sex). Discussion/Conclusion: The relationships among BMI, WHR and CI exhibit an opposite trend. A low BMI or high WHR was positively associated with CI, which was more prominent in males for a low BMI, and in females for a high WHR.