Status of Metabolomic Measurement for Insights in Alzheimer's Disease Progression-What Is Missing?

Alzheimer's disease (AD) is an aging-related neurodegenerative disease, leading to the progressive loss of memory and other cognitive functions. As there is still no cure for AD, the growth in the number of susceptible individuals represents a major emerging threat to public health. Currently, the pathogenesis and etiology of AD remain poorly understood, while no efficient treatments are available to slow down the degenerative effects of AD. Metabolomics allows the study of biochemical alterations in pathological processes which may be involved in AD progression and to discover new therapeutic targets. In this review, we summarized and analyzed the results from studies on metabolomics analysis performed in biological samples of AD subjects and AD animal models. Then this information was analyzed by using MetaboAnalyst to find the disturbed pathways among different sample types in human and animal models at different disease stages. We discuss the underlying biochemical mechanisms involved, and the extent to which they could impact the specific hallmarks of AD. Then we identify gaps and challenges and provide recommendations for future metabolomics approaches to better understand AD pathogenesis.

[Rat serum and heart tissue metabolomics in myocardial ischemia based on liquid chromatography-mass spectrometry].

A rat model with isoproterenol (ISO)-induced myocardial ischemia was obtained. Liquid chromatography-mass spectrometry (LC-MS)was conducted on the serum and heart tissue metabolites of normal and model rats. Principal component analysis (PCA) and differentiation analysis of supervised partial least-squares method (PLS-DA) were applied to the metabolomics data for multidimensional statistical analysis, and the resulting biomarkers were screened. Compared with the normal group, 18 different endogenous metabolites in plasma and tissues were detected, including the products of arginine and proline metabolism; glycine, serine, and threonine metabolism; glutamine and glutamate metabolism; and taurine and hypotaurine metabolism. These metabolites can be used as important biomarkers for myocardial ischemia. The results of this study can help reveal the pathogenesis of myocardial ischemia and aid clinical diagnosis.

[Effects of probucol, aspirin and atorvastatin combination therapy upon atherosclerosis].

OBJECTIVE: To investigate the effects of probucol, aspirin and atorvastatin (PAS) combination therapy upon atherosclerosis. METHODS: A total of 436 patients with coronary artery disease were selected and randomly divided into control group (aspirin 100 mg, atorvastatin 10 mg daily) and PAS group (aspirin 100 mg, atorvastatin 10 mg and probucol 0.25 g daily). After a 1-year treatment course, 378 cases remained in the study (201 in control group vs. 177 in PAS group). These patients were followed for throughout the study course and their serum levels of high density lipoprotein (HDL), ox-LDL, TXB2 and MMP-9 were measured at 6 and 12 months respectively. Twenty cases were diagnosed with carotid artery plaque by carotid ultrasound and 16 cases remained in the PAS group. They were followed with ultrasound for plaque thickness. RESULTS: In the control group, the pre-treatment level of MMPs and ox-LDL were not statistically different from the post-treatment level (P > 0.05). In the PAS group, the pre-treatment level of ox-LDL was (23.46 +/- 0.01) mmol/L and the post-treatment level (16.13 +/- 0.02) mmol/L. There was a decrease of 31.7% (P < 0.05). The pre-treatment level of MMPs and MMP-9 in the control group was not statistically different from the post-treatment level. The pre-treatment level of MMP-9 in the PAS group was (7.15 +/- 0.01) mmol/L and the post-treatment level (4.19 +/- 0.02) mmol/L. There was a decrease of 42.4% (P < 0.05). During the course of follow-up, the hospitalization rate, angina recurrence rate, myocardial infarction rate and mortality rate for the control group were 23 (11.4%), 28 (13.9%), 4 (2.0%) and 2 (1.0%) respectively. In the PAS group, the corresponding values were 6 (3.4%), 13 (7.3%), 1 (0.6%) and 0 respectively. All parameters of adverse events showed a significant decrease in the PAS group (P < 0.05). Among the cases with carotid plaque, the pretreatment measurements of intima thickness and plaque thickness were (0.103 +/- 0.002) cm and (0.248 +/- 0.001) cm while the post-treatment corresponding measurements (0.097 +/- 0.001) cm and (0.209 +/- 0.002) cm respectively. There was a significant difference between the PAS group and the control group (P < 0.05). CONCLUSION: Antioxidant probucol significantly inhibits the generation of ox-LDL and MMP-9. PAS therapy also reduces the plaque thickness and decreases the rate of adverse event in patients with atherosclerosis. Antioxidants can be considered as a new adjunct therapy in the treatment of atherosclerosis.