Plasma Sphingolipid Profile in Association with Incident Metabolic Syndrome in a Chinese Population-Based Cohort Study.

Although bioactive sphingolipids have been shown to regulate cardiometabolic homeostasis and inflammatory signaling pathways in rodents, population-based longitudinal studies of relationships between sphingolipids and onset of metabolic syndrome (MetS) are sparse. We aimed to determine associations of circulating sphingolipids with inflammatory markers, adipokines, and incidence of MetS. Among 1242 Chinese people aged 50-70 years who completed the 6-year resurvey, 76 baseline plasma sphingolipids were quantified by high-throughput liquid chromatography-tandem mass spectrometry. There were 431 incident MetS cases at 6-year revisit. After multivariable adjustment including lifestyle characteristics and BMI, 21 sphingolipids mainly from ceramide and hydroxysphingomyelin subclasses were significantly associated with incident MetS. Meanwhile, the baseline ceramide score was positively associated (RRQ4 versus Q1 = 1.31; 95% CI 1.05, 1.63; ptrend = 0.010) and the hydroxysphingomyelin score was inversely associated (RRQ4 versus Q1 = 0.60; 95% CI 0.45, 0.79; ptrend < 0.001) with incident MetS. When further controlling for clinical lipids, both associations were attenuated but remained significant. Comparing extreme quartiles, RRs (95% CIs) of MetS risk were 1.34 (95% CI 1.06, 1.70; ptrend = 0.010) for ceramide score and 0.71 (95% CI 0.51, 0.97; ptrend = 0.018) for hydroxysphingomyelin score, respectively. Furthermore, a stronger association between ceramide score and incidence of MetS was evidenced in those having higher inflammation levels (RRQ4 versus Q1 1.57; 95% CI 1.16, 2.12; pinteraction = 0.004). Our data suggested that elevated ceramide concentrations were associated with a higher MetS risk, whereas raised hydroxysphingomyelin levels were associated with a lower MetS risk beyond traditional clinical lipids.

[Protective effects of salidroside on oxidative damage in fatigue mice].

OBJECTIVE: To study the protective effects of salidroside on oxidative damage in fatigue mice. METHODS: Thirty-two male Kunming mice were randomly divided into four groups based on body weight: normal control group, salidroside group, training group and salidroside plus training group. The mice in the normal control group and the training group were given distilled water and mice in the salidroside group and the salidroside plus training group were given 180 mg/ (kg * d) salidroside for 15 days. At 30 min after the last administration, the mice in the training group and the salidroside plus training group were forced to swim for 120 min. Finally, all the mice were killed. The activities of lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-myocardial band isoenzyme (CK-MB) in plasma were determined by an auto-biochemistry analyzer. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malonaldehyde (MDA) in liver tissue were also detected. The changes of ultrastructures of the skeletal muscle and cardiac muscle were observed under an electron microscope. RESULTS: Compared with no swimming, long-time swimming could significantly increase the activities of LDH, CK and CK-MB in plasma (P < 0.05, P < 0.01), while salidroside could significantly decrease the activities of CK and CK-MB in plasma induced by long-time swimming (P < 0.05, P < 0.01). There existed interactions in LDH, CK and CK-MB activities between salidroside and long-time swimming (P < 0.05). Compared with no swimming, long-time swimming could significantly decrease the SOD and GSH-Px activities and increase the MDA content in liver tissue (P < 0.01). Salidroside could significantly increase the GSH-Px and SOD activities and decrease the MDA content in liver tissue (P < 0.05, P < 0.01). However, there were no interactions in GSH-Px activity and MDA content between salidroside and long-time swimming (P < 0.05). After long-time swimming, more ultrastructural lesions were found in the cardiac muscle and skeletal muscle in the training group than in the salidroside plus training group. CONCLUSION: Salidroside may play a role in protecting the mice from oxidative damage caused by long-time endurance training.

[A novel bifunctional in vivo mutation detection system].

A shuttle plasmid pMCLacI/neo with two copies of LacI was integrated into mouse genome and a novel system which could detect in vivo mutation of both expression and silence genes was constructed, enabling the comparative analysis of their mutation spectra and mutant frequencies. 486 fertilized eggs from C57BL/6 mice with microinjected pMCLacI/neo plasmid were transferred into oviducts of 18 pseudo-pregnant mice, and 32 alive offsprings were screened and identified by using PCR and Southern blotting. Genomes of 5 mice had pMCLacI/neo plasmid integrated, as verified by Southern blot after the PCR screening. Only one of the two LacI in pMCLacI/neo was in expression state; and this established a model, that the status in vivo of both gene expression and silencing could be simulated. This kind of mice might be used as a novel bifunctional mutation detection system in vivo.

[A new strategy for detecting Lac I mutants based on pMCLac I/neo transgenic mice].

We studied a novel mutation detection method of the two Lac I target genes in pMCLac I/neo transgenic mice. The transgenic mice that contain two types of Lac I genes in pMCLac I/neo vector are different from the transgenic mice carrying only one target gene. Therefore a novel method to detect mutation quickly and efficiently has become a new project after the establishment of pMCLac I/neo transgenic mice. In this paper, a positive selection system--M9/L is used. The result showed that M9/L positive selection system was able to detect the two Lac I target genes, suggesting that it is a rapid and effective method to detect the target mutations in the pMCLac I/neo transgenic mouse.

Quantitative detection of single amino acid polymorphisms by targeted proteomics.

Single-nucleotide polymorphisms (SNPs) are recognized as one kind of major genetic variants in population scale. However, polymorphisms at the proteome level in population scale remain elusive. In the present study, we named amino acid variances derived from SNPs within coding regions as single amino acid polymorphisms (SAPs) at the proteome level, and developed a pipeline of non-targeted and targeted proteomics to identify and quantify SAP peptides in human plasma. The absolute concentrations of three selected SAP-peptide pairs among 290 Asian individuals were measured by selected reaction monitoring (SRM) approach, and their associations with both obesity and diabetes were further analyzed. This work revealed that heterozygotes and homozygotes with various SAPs in a population could have different associations with particular traits. In addition, the SRM approach allows us for the first time to separately measure the absolute concentration of each SAP peptide in the heterozygotes, which also shows different associations with particular traits.