The role of GLP-1/GIP receptor agonists in Alzheimer's disease.

BACKGROUND: New glucagon-like peptide-1 (GLP-1) analogues developed in recent years have a long half-life and offer further prospects for clinical application. At present, the neuroprotection of GLP-1 analogues in Alzheimer's disease (AD) has just begun to be explored. OBJECTIVES: To investigate how glucagon-like peptide-1 (liraglutide) plays a protective role in AD by regulating tau activation and BACE1 expression. MATERIAL AND METHODS: Human neuroblastoma cell line SH-SY5Y cells were cultured in vitro and pretreated with different concentrations of liraglutide, and then treated with different concentrations of okadaic acid (OA) in order to observe the apoptosis of the SH-SY5Y cells. After liraglutide treatment, the apoptosis of neurons in AD rats was detected using flow cytometry, and tau activation and ß-site APP cleaving enzyme 1 (BACE1) expression were detected using western blot. RESULTS: Different concentrations of OA were able to induce apoptosis of SH-SY5Y cells in a dose-dependent manner. Different concentrations of liraglutide were used to pretreat SH-SY5Y cells, which were able to protect the SH-SY5Y cells from apoptosis induced by OA. Okadaic acid significantly increased tau activation and BACE1 expression in the SH-SY5Y cells, which was blocked with liraglutide pretreatment. The results of a water maze experiment showed that liraglutide had significant protective effects on memory and cognitive ability in AD rats induced with OA, inhibited apoptosis of neural cells in AD rats, and inhibited tau activation and BACE1 expression of neural cells in AD rats induced with OA. CONCLUSIONS: Liraglutide has a protective effect on AD in vivo and in vitro, which may be mediated by preventing neuronal apoptosis and inhibiting the activation of tau and the expression of BACE1.

Non alcoholic steatohepatitis a precursor for hepatocellular carcinoma development.

Hepatocellular carcinoma (HCC) is increasing in prevalence and is one of the most common cancers in the world. Chief amongst the risks of attaining HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The later has been shown to promote non alcoholic fatty liver disease, which can lead to the inflammatory form non alcoholic steatohepatitis (NASH). NASH is a complex metabolic disorder that can impact greatly on hepatic function. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give an overview of the recent novel mechanisms published that have been associated with NASH and subsequent HCC progression. We will focus our discussion on inflammation and gut derived inflammation and how they contribute to NASH driven HCC.

Development and validation of a capillary zone electrophoresis method for the determination of benzalkonium chlorides in ophthalmic solutions.

A systematic investigation of optimal conditions for determining the benzalkonium chlorides in ophthalmic products by capillary zone electrophoresis (CZE) was presents. The most effective separation conditions was 40 mM phosphate buffer with 40% acetonitrile at pH 4.0, and the sample hydrodynamic injection of up to 10 s at 2 p.s.i. (1 p.s.i.=6892.86 Pa) (approximately 35.15 nl), and an applied voltage of 15 kV. The reproducibility of the migration time and quantitative analysis can be improved by using internal standard, triethylbenzylammonium chloride, giving the relative standard deviation less than 0.2% for the relative migration times, and 5.0-7.8% for the relative peak areas. A good linearity of CZE analysis was obtained in the range of 1.0-20 microg/ml with r2 values of above 0.99. The established HPLC with UV-Vis detection was applied to evaluate the CZE method, and compatible results were obtained by using CZE with much shorter analysis time and a small quantity of solvents consumed.