Genome-wide association studies (GWAS) have identified one single-nucleotide polymorphism (SNP) rs9271192 within HLA-DRB1 as a risk factor for Alzheimer's disease (AD) in Caucasians. The effect of rs9271192 on AD needed to be verified in other ethnic cohorts. In order to evaluate the association between HLA-DRB1 rs9271192 polymorphism and late-onset AD (LOAD) in the Northern Han Chinese population, we recruited 982 LOAD patients and 1344 sex- and age-matched healthy controls. The results showed that HLA-DRB1 rs9271192 was associated with LOAD (genotype P = 0.015, allele P = 0.04). The results of logistic regression revealed the C allele homozygosity strongly increased the risk of LOAD under a recessive model in the total sample (P = 0.004, OR =2.069, 95% CI = 1.262–3.434). When these data were stratified by apolipoprotein E (APOE) ε4 status, the observed association was confined to APOE ε4 non-carriers (additive model: P=0.048, OR =1.191, 95% CI =1.001–1.417; recessive model: P < 0.001, OR = 2.601, 95% CI =1.519–4.566). Furthermore, meta-analysis after sensitive analysis confirmed that rs9271192 within HLA-DRB1 increased the risk of LOAD (OR = 1.12, 95% CI = 1.08–1.15). To summarize, the C allele in HLA-DRB1 rs9271192 may be an independent risk factor for LOAD.
Context Alpinetin, the major active constitutes of Alpinia katsumata Hayata (Zingiberaceae), has been demonstrated to possess the activity of anti-breast cancer. Cytochrome P450 enzymes (CYP450s) plays vital roles in the biotransformation of various drugs. Objective To assess the effect of alpinetin on the activity of CYP450s and estimate the inhibition characteristics. Materials and methods The activity of CYP450s was evaluated in pooled human liver microsomes with corresponding substrates and marker reactions. The effect of alpinetin was compared with blank control (negative control) and corresponding inhibitors (positive control). The dose-dependent and time-dependent experiments were conducted in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM alpinetin and incubated for 0, 5, 10, 15, and 30 min. Results Alpinetin suppressed CYP3A4, 2C9, and 2E1 activity. All the inhibitions were significantly influenced by alpinetin contration with the IC 50 values of 8.23 μM (CYP3A4), 12.64 μM (CYP2C9), and 10.97 μM (CYP2E1), respectively. The inhibition of CYP3A4 was fitted with the non-competitive model with a Ki value of 4.09 μM and was time-dependent with KI and Kinact values of 4.67 min and 0.041 μM −1 , respectively. While CYP2C9 and 2E1 were inhibited by alpinetin competitively with Ki values of 6.42 (CYP2C9) and 5.40 μM (CYP2E1), respectively, in a time-independent manner. Discussion and conclusion The in vitro inhibitory effect of alpineticn on CYP3A, 2C9, and 2E1 implied the potential interaction of alpinetin or its origin herbs with the drugs metabolised by those CYP450s, which needs further in vivo validation.
Aplastic anemia, an uncommon and life-threatening blood disorder, is featured by pancytopenia and trilineage bone marrow (BM) aplasia. 1 Aplastic anemia is considered as a special autoimmune disease that targeting the BM. Aberrant immunity, mainly autoreactive T lymphocytes attacking on hemopoietic progenitor cells, has been considered to play indispensably crucial roles in the pathogenesis of aplastic anemia. [1][2][3][4] Abnormally polarized Th1 cells, elevated Th17 cells, and activated CD8 + cytotoxic T cells were proven to be involved in the immune-mediated damage of hematopoiesis by the following two ways: indirect induction of hematopoietic cells apoptosis by excessively releasing hematopoietic negative regulators, such as interferon (IFN)γ and tumor necrosis factor (TNF)α; and direct damage to autologous hematopoietic stem cells. [4][5][6][7] Further analysis confirmed that regulatory T cells (Tregs) and other cytokines, for
Background: Cancer metabolism and specifically lipid metabolism play an important role in breast cancer (BC) progression and metastasis. However, the role of lipid metabolism-associated genes (LMGs) in the diagnosis of breast cancer remains unknown. Methods: The expression profiles and clinical follow-up information of BC were downloaded from The Cancer Genome Atlas (TCGA), and metabolic genes were downloaded from the Gene Set Enrichment Analysis (GSEA) dataset. Univariate cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed on the differentially expressed metabolism-related genes. Then, the formula of the metabolism-related risk model was composed, and the risk score of each patient was calculated. The breast cancer patients were divided into high-risk and low-risk groups with a cutoff of the median expression value of the risk score, and the prognostic analysis was also used to analyze the survival time between these two groups. Finally, we analyzed the expression, interaction and correlation among the lipid metabolism-associated genes risk model.Results: The results from the prognostic analysis indicated that the survival was significantly poorer in the high-risk group than in the low-risk group in TCGA, single-sample gene set enrichment analysis (ssGSEA) shows it is plausible that lipid metabolism is highly correlated with tumor immunity.Conclusion: Lipid metabolism-associated genes may become a new prognostic indicator predicting the survival of BC patients. The prognostic genes (n=16) may help provide new strategies for tumor therapy.
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