Detection of potential new biomarkers of atherosclerosis by probe electrospray ionization mass spectrometry

Introduction

Atherosclerotic diseases are the leading cause of death worldwide. Biomarkers of atherosclerosis are required to monitor and prevent disease progression. While mass spectrometry is a promising technique to search for such biomarkers, its clinical application is hampered by the laborious processes for sample preparation and analysis.

Methods

We developed a rapid method to detect plasma metabolites by probe electrospray ionization mass spectrometry (PESI-MS), which employs an ambient ionization technique enabling atmospheric pressure rapid mass spectrometry. To create an automatic diagnosis system of atherosclerotic disorders, we applied machine learning techniques to the obtained spectra.

Results

Using our system, we successfully discriminated between rabbits with and without dyslipidemia. The causes of dyslipidemia (genetic lipoprotein receptor deficiency or dietary cholesterol overload) were also distinguishable by this method. Furthermore, after induction of atherosclerosis in rabbits with a cholesterol-rich diet, we were able to detect dynamic changes in plasma metabolites. The major metabolites detected by PESI-MS included cholesterol sulfate and a phospholipid (PE18:0/20:4), which are promising new biomarkers of atherosclerosis.

Conclusion

We developed a remarkably fast and easy method to detect potential new biomarkers of atherosclerosis in plasma using PESI-MS.

     

Association between the MMP-9−1562 C>T polymorphism and the risk of stroke: a meta-analysis

Matrix metalloproteinase (MMP)-9 so far is identified as extremely large and complicated MMP family member. Recently, dozens of studies have explored the association between a promoter polymorphism (?1562 C>T) in MMP-9 and stroke susceptibility. However, the conclusions of these studies still remain equivocal. Therefore, our current meta-analysis was conducted to investigate whether or not the MMP-9 promoter polymorphism is related to the risk of stroke. Electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library and the Chinese Biomedical Literature Database) were searched to obtain all the available studies investigating this polymorphism and stroke from inception to October 2013. Overall and subgroup analyses were rigorously conducted after data extraction. Pooled odds ratio (OR) corresponding to 95 % confidence interval (CI) were estimated. The statistical analysis was performed using Review Manager 5.2. Totally, seven studies involving 1,624 cases and 1,525 controls were identified. The overall results suggested that there was no association of the C?1562T variant on stroke risk under the T allele versus C allele [OR _{T vs. C} 0.98, 95 % CI (0.84, 1.15), P = 0.84], the dominant model [OR _{TT+TC vs. CC} 0.95, 95 % CI (0.81, 1.13), P = 0.59], the recessive model [OR _{TT vs. TC+CC} 1.55, 95 % CI (0.86, 2.81), P = 0.15], the homozygote comparison [OR _{TT vs. CC} 1.48, 95 % CI (0.82, 2.68), P = 0.20] and the heterozygote comparison [OR _{TC vs. CC} 0.93, 95 % CI (0.78, 1.10), P = 0.38]. In the subgroup analyses by ethnicity, age, stroke type and source of controls, no significant relations were observed in any genetic models. Our results indicated that MMP-9?1562 C>T polymorphism was not a risk factor for stroke. Further studies should focus on gene–gene and gene–environment interactions, and provide a more convincing explanation for this association.     

Molecular Phylogeny and Taxonomy of Two Novel Brackish Water Hypotrich Ciliates,with the Establishment of a New Genus,Antiokeronopsis gen. n. (Ciliophora,Hypotrichia)

Two novel brackish water urostyloid ciliates, Anteholosticha paramanca sp. n. and Antiokeronopsis flava gen. n., sp. n., isolated from the Shenzhen Mangrove Nature Protection Area on the coast of the South China Sea, were investigated using live observation and protargol impregnation techniques. Anteholosticha paramanca sp. n. is characterized by its spherical yellowish cortical granules arranged in lines, shortened midventral complex and three transverse cirri. Morphogenesis is similar to that in Anteholosticha manca. The new genus Antiokeronopsis is diagnosed by having a continuous adoral zone of membranelles, frontal cirri arranged in a bicorona, midventral complex composed of midventral pairs only, one marginal cirral row on each side, the presence of frontoterminal and transverse cirri, and the lack of buccal and caudal cirri. The type species A. flava sp. n. is characterized by its elongated body shape, brown to yellowish body color and two types of cortical granules. Small subunit ribosomal RNA gene sequence data justify the classification of both species. Phylogenetic analyses indicate that A. paramanca clusters with Bakuella subtropica within a clade that includes two other Anteholosticha species, while Antiokeronopsis groups within the core urostylids and is most closely related to the well‐known genera Pseudokeronopsis and Uroleptopsis.     

Five genes as a novel signature for predicting the prognosis of patients with laryngeal cancer

In this study, we purpose to investigate a novel five-gene signature for predicting the prognosis of patients with laryngeal cancer. The laryngeal cancer datasets were obtained from The Cancer Genome Atlas (TCGA). Both univariate and multivariate Cox regression analysis was applied to screening for prognostic differential expressed genes (DEGs), and a novel gene signature was obtained. The performance of this Cox regression model was tested by receiver operating characteristic (ROC) curves and area under the curve (AUC). Further survival analysis for each of the five genes was carried out through the Kaplan-Meier curve and Log-rank test. Totally, 622 DEGs were screened from the TCGA datasets in this study. We construct a five-gene signature through Cox survival analysis. Patients were divided into low- and high-risk groups depending on the median risk score, and a significant difference of the 5-year overall survival was found between these two groups (P < .05). ROC curves verified that this five-gene signature had good performance to predict the prognosis of laryngeal cancer (AUC = 0.862, P < .05). In conclusion, the five-gene signature consist of EMP1, HOXB9, DPY19L2P1, MMP1, and KLHDC7B might be applied as an independent prognosis predictor of laryngeal cancer.     

The regulation,function, and role of lipophagy,a form of selective autophagy,in metabolic disorders

Autophagy is a conserved method of quality control in which cytoplasmic contents are degraded via lysosomes. Lipophagy, a form of selective autophagy and a novel type of lipid metabolism, has recently received much attention. Lipophagy is defined as the autophagic degradation of intracellular lipid droplets (LDs). Although much remains unknown, lipophagy appears to play a significant role in many organisms, cell types, metabolic states, and diseases. It participates in the regulation of intracellular lipid storage, intracellular free lipid levels (e.g., fatty acids), and energy balance. However, it remains unclear how intracellular lipids regulate autophagy. Impaired lipophagy can cause cells to become sensitive to death stimuli and may be responsible for the onset of a variety of diseases, including nonalcoholic fatty liver disease and metabolic syndrome. Like autophagy, the role of lipophagy in cancer is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets. These studies have stimulated increasing interest in the role of lipophagy in the pathogenesis and treatment of cancer and other human diseases.Subject terms: Autophagy, Mechanisms of disease