OBJECTIVES: To investigate the regulatory role of nucleotide-bound oligomerized domain-like receptor containing pyrin-domain protein 6 (NLRP6) in liver lipid metabolism and non-alcoholic fatty liver disease (NAFLD). METHODS: Mouse models with high-fat diet (HFD) feeding for 16 weeks (n=6) or with methionine choline-deficient diet (MCD) feeding for 8 weeks (n=6) were examined for the development of NAFLD using HE and oil red O staining, and hepatic expressions of NLRP6 were detected with RT-qPCR, Western blotting, and immunohistochemical staining. Cultured human hepatocytes (LO2 cells) with adenovirus-mediated NLRP6 overexpression or knock-down were treated with palmitic acid (PA) in the presence or absence of compound C (an AMPK inhibitor), and the changes in cellular lipid metabolism were examined by measuring triglyceride, ATP and β-hydroxybutyrate levels and using oil red staining, RT-qPCR, and Western blotting. RESULTS: HFD and MCD feeding both resulted in the development of NAFLD in mice, which showed significantly decreased NLRP6 expression in the liver. In PA-treated LO2 cells, NLRP6 overexpression significantly decreased cellular TG content and lipid deposition, while NLRP6 knockdown caused the opposite effects. NLRP6 overexpression in PA-treated LO2 cells also increased mRNA and protein expressions of PGC1A and CPT1A, levels of ATP and β-hydroxybutyrate, and the phosphorylation level of AMPK pathway; the oxidative decomposition of lipids induced by Ad-NLRP6 was inhibited by the use of AMPK inhibitors. CONCLUSIONS NLRP6 overexpression promotes lipid oxidation and decomposition through AMPK/CPT1A/PGC1A to alleviate lipid deposition in hepatocytes.
Non-alcoholic Fatty Liver Disease/metabolism* ; Animals ; Hepatocytes/metabolism* ; Lipid Metabolism ; Mice ; Humans ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; AMP-Activated Protein Kinases/metabolism* ; Carnitine O-Palmitoyltransferase/metabolism* ; Diet, High-Fat ; Male ; Mice, Inbred C57BL ; Signal Transduction

In this study, the distribution of five Alzheimer's disease (AD)-related single nucleotide polymorphisms (SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs, clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College (CAMS/PUMC) Human Brain Bank. APOE ε4 (OR = 4.482, P = 0.004), the RS2305421 GG genotype (adjusted OR = 4.397, P = 0.015), and the RS10498633 GT genotype (adjusted OR = 2.375, P = 0.028) were associated with a higher score on the ABC (Aβ plaque score, Braak NFT stage, and CERAD neuritic plaque score) dementia scale. These results advance our understanding of the pathogenesis of AD, the relationship between pathological diagnosis and clinical diagnosis, and the SNPs in the Han population for future research.
ADAM10 Protein ; genetics ; Adult ; Aged ; Aged, 80 and over ; Alzheimer Disease ; genetics ; pathology ; Amyloid Precursor Protein Secretases ; genetics ; Antiporters ; genetics ; Apolipoprotein E4 ; genetics ; Asian Continental Ancestry Group ; genetics ; Brain ; pathology ; Cognitive Dysfunction ; genetics ; pathology ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide

Autopsy ; Brain ; metabolism ; pathology ; Gene Expression ; physiology ; Humans ; Transcriptional Activation ; physiology

Objective To discuss the technical method,safety and clinical efficacy of CT-guided 125I radioactive seed implantation for the treatment of mediastinal lymph node metastases.Methods CT-guided 125I radioactive seed implantation was carried out in 11 patients with mediastinal lymph node metastases.Before 125I seed implantation,the interstitial brachytherapy treatment planning system (TPS) was employed to formulate a treatment plan.The particles with radioactivity of (1.11-2.96) × 107Bq (0.3-0.8 mCi) were used for the implantation.Postoperative complications were recorded.The local lesion control rate and the effective rate of pain relief were evaluated at one,3,6 and 12 months after 125I seed implantation.Results After 125I seed implantation,pneumothorax occurred in 3 patients,tracheal fistula in one patient,and pulmonary infection in one patient.The local lesion control rates at one,3,6 and 12 months were 81.8％,90.9％,72.7％ and 72.7％ respectively;the effective rate of pain relief at one week,one,3,6 and 12 months were 100％,90.9％,90.9％,81.8％ and 72.7％ respectively.Conclusion For the treatment of mediastinal lymph node metastases,CT-guided radioactive 125I seed implantation is less-invasive with less complications,and it carries reliable local lesion control rate.Therefore,this technique is a safe therapeutic means.

To optimize the extraction technology of the total saponins in Dipsaci Radix, the extraction efficiency of total saponins was investigated with respecting to three variables including time, ethanol concentration and liquid-to-solid ratio. On the basis of a series of one-factor-at-a-time experiments, a polynomial regression model equation was fitted by the combined use of central composite experimental design and regression analysis. By analyzing the regression model using response surface analysis, the optimum extraction conditions of total saponins from Dipsaci Radix were identified as follows: 7 times of 55% alcohol, refluxing 3 times, 2.8 hours every time, and the extraction efficiency of total saponins was up to 0.201 1 g·g-1 and the asperosaponin Ⅵ was up to 0.015 4 g·g-1 under the optimized conditions. Confirmatory experiment indicated the good prediction ability of the established model and provided the basis for further development and utilization of Dipsaci Radix.