Plasma levels of ceramides relate to ischemic stroke risk and clinical severity.

Recent studies have suggested that specific plasma ceramides are independently associated with atherosclerosis and cardiovascular diseases, but it is currently unknown whether plasma ceramide levels are associated with ischemic stroke. Here, we examined whether ceramides were associated with both ischemic stroke risk and clinical severity at admission. We measured three previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/22:0), and Cer(d18:1/24:0)] in 202 patients with acute ischemic stroke and 202 age and sex matched control cases. Plasma ceramides levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay at baseline. The median age of the 202 stroke patients was 66 (interquartile range [IQR], 58-75) years and 54.0 % were men. Plasma levels of C16:0, C22:0, and C24:0 ceramides in stroke patients were significantly higher than in those control cases (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of ischemic stroke (odd ratio [OR] for one IQR increase: 2.15[1.42-2.99]; 2.90[2.13-4.01] and 1.29[1.10-1.69]; respectively). At admission, 103 patients (51.0 %) had a minor stroke (NIHSS < 6). In these patients, plasma levels of C16:0, C22:0, and C24:0 ceramides were lower than that observed in patients with moderate-to-high clinical severity (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of moderate-to-high stroke (OR for one IQR increase: 2.96 [2.05-4.22], 3.03 [2.01-4.25] and 1.72 [1.25-3.31], respectively). An elevated plasma levels of ceramides were predictors of both risk and severity at admission in ischemic stroke patients. The underlying mechanisms of these associations remain to be investigated.

[Study on oriented differentiation of bone marrow mesenchymal stem cells by fibroblast in rat uterine ligament with mechanical stretch].

OBJECTIVE: To investigate the effect on the differentiation of bone marrow mesenchymal stem cells (BMSC) with non-contact co-culture with mechanical stimulated ligament fibroblasts. METHODS: A cyclic 10% uniaxia strain at 1 Hz was applied on rat pelvic ligament fibroblasts, then were co-cultured with BMSC for 3, 6 and 12 days in non-contact condition. The protein expression of collagen I, III in BMSC were detected by SP method and revealed by the mean gray value. The mRNA expressions of collagens type I and type III in the BMSCs were measured with real-time (RT)-PCR, and the results were indicated by the ratio between the mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). RESULTS: (1) Protein expression: after 3 days co-culture with pelvic ligament fibroblasts, expression of collagen I and III in BMSC are 82.4±3.4 and 76.8±2.5. When compared with 80.2±2.6 and 74.6±1.1 in BMSC without co-culture, there was no significant difference (P>0.05). After 6 days co-culture with pelvic ligament fibroblasts, the expression of collagen I and III of 126.6±2.2 and 118.6±1.4 in BMSC were significantly higher than 82.7±3.0 and 76.2±1.3 in BMSC without co-culture (P<0.05). Similarly, after 12 days co-culture with pelvic ligament fibroblasts, the expression of collagen I and III of 135.3±3.4 and 128.7±2.6 in BMSC were significantly higher than 86.6±1.3 and 81.8±1.4 in BMSC without co-culture (P<0.05). (2) mRNA expression: after 3 days co-culture with pelvic ligament fibroblasts, the mRNA expression of type I and type III collagens in BMSC are 2.10±0.20 and 1.20±0.30. When compared with mRNA expression of 2.01±0.12 and 1.13±0.21 in BMSC without co-culture, no significant difference were observed (P>0.05). After 6 days co-culture with pelvic ligament fibroblasts, the mRNA expressions of type I and type III collagens mRNA were 5.60±0.21 and 2.61±0.20, which were significantly higher than 3.70±0.33 and 1.82±0.14 in BMSC without coculture (P<0.05). After 12 days co-culture with pelvic ligament fibroblasts, the mRNA expressions of type I and type III collagens of 5.91±0.31 and 2.92±0.23 were significantly higher than 4.04±0.21 and 2.04±0.13 in BMSC without co-culture (P<0.05). CONCLUSION: Non-contact co-culture with mechanical stretch stimulated ligament fibroblasts, it might promote synthesis of types Iand III collagen in rat BMSCs and induced BMSC differentiated into pelvic ligament fibroblasts.