Septic acute kidney injury (AKI) and myocardial dysfunction are leading causes of mortality with no accepted method of therapy. In this study we demonstrate the role of growth differentiating factor 15 (GDF15) in septic AKI and myocardial dysfunction using a murine lipopolysaccharide (LPS)-induced sepsis model and an in vitro cell culture system. Data show that GDF15 deficiency augments inflammatory response and exacerbates renal and cardiac injury induced by LPS, while over-expression of GDF15 protects the kidney and heart from LPS-induced organ dysfunction. Therefore, this study highlights the therapeutic potential of GDF15 in the treatment of endotoxin-induced sepsis.
Aim: Currently, there are almost 100 genes related to Alzheimer's disease (AD), and studies have indicated that apolipoprotein E (APO E) e4 allele is a genetic risk factor of AD. However, there have been no reports of the distributions of APO E genotypes and allele frequencies in Uighur and Han AD patients. Methods: We analyzed APO E gene polymorphism in 209 AD cases diagnosed based on National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association and 220 non-dementia controls. We used polymerase chain reactionrestriction fragment length polymorphism methods as the basis of this epidemiological survey. Results: In the AD and control groups, there are no statistically significant differences in APO E genotypes and allele frequency between the Uighur and Han ethnicities (P < 0.05). In the AD group, the e3/4 genotype (28.2%) and e4 allele frequency (14.8%) occurred at a higher rate than in the control (13.2% and 8.0%, respectively; P < 0.05). This distinction remained true within each ethnicity; the e3/4 genotype and e4 allele frequency are higher in the AD groups (Uighur, 30.6% and 15.8%, respectively; Han, 25.5% and 13.8%, respectively) than in the control groups (Uighur, 14.5% and 9.4%, respectively; Han, 11.7% and 6.3%, respectively; P < 0.05). Conclusions: The distribution of APO E genotype and allele frequency does not differ between the Uighur and Han ethnicities. The APO E e4 allele is a risk factor of AD for both populations.
The secretive Klotho protein is an anti-aging regulatory hormone that plays a physiological role in many target organs. The present study aims to investigate the correlation between Klotho gene and mild cognitive impairment (MCI) in Uygur and Han populations in Xinjiang. From July 2008 to April 2014, stratified random multistage cluster sampling was used in combination with the methods of on-site questionnaire and household survey to conduct a cross-sectional MCI investigation on selected Uygur and Han subjects aged over 60 years old in Xinjiang region. 323 Uygur and Han MCI patients were randomly selected and matched with 343 subjects in the normal control group. SNaPshot technique was used to detect the polymorphisms of Klotho gene. A case-control associated analysis was conducted to analyze the genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the MCI group and the normal control group. The polymorphisms of rs1207568 and rs9536314/rs9527025 loci in Klotho gene were different among MCI populations in Xinjiang, and after group assignments based on ethnic background, the polymorphisms of rs1207568 and rs9536314/rs9527025 loci were associated with the Uygur MCI population and were not relevant to the Han MIC population. The frequencies of mutational alleles of rs9536314/rs9527025 locus in the Uygur population were significantly higher than those in the Han population. The genotype and allele frequencies of rs1207568 locus in the Uygur and Han populations were similar. The polymorphisms of rs1207568 and rs9536314/rs9527025 loci in Klotho gene may be associated with the Uygur MCI population in Xinjiang.
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