Moderate walnut consumption improved lipid profile,steroid hormones and inflammation in trained elderly men: a pilot study with a randomized controlled trial

The present study aimed to investigate the effect of walnut consumption on lipid profile, steroid hormones and inflammation in trained elderly men performing concurrent (resistance and endurance) training. Twenty healthy elderly males were divided into two matched groups, in a randomized controlled trial, that trained three sessions per week: concurrent training + dietary walnut consumption (15 g/day for six weeks, CTW: n = 10); concurrent training + control diet (CT: n = 10). Fasting blood samples were taken 48 hours before and after intervention for biochemical assessments. levels of high-density lipoprotein (HDL) increased only in CTW compared to baseline (19.8%, p < 0.01). Total cholesterol (TC), low-density lipoprotein (LDL) and triglyceride (TG) levels significantly decreased only for CTW (i.e., 13%, 18%, and 18.5% at p < 0.01 for all). Testosterone (T) increased after the training compared to pre-training for CTW and CT (10.3%, p < 0.01, 4.27% p < 0.05, respectively), but the increase was significantly higher in CTW (p < 0.05). Serum cortisol (C) was lower for CTW compared to CT (p < 0.01). C-reactive protein (CRP) decreased in CTW in comparison with CT. The present study revealed that 6-week moderate walnut supplementation (15 g/day) improved lipid profile, steroid hormones and systematic inflammation in aged men performing concurrent training. These findings could be attributable to the potential effect of polyunsaturated fatty acids (PUFA) contained in walnut (linoleic acid, n-6; linolenic acid, n-3).     

Downregulation of neutral ceramidase by gemcitabine: Implications for cell cycle regulation

Gemcitabine (GMZ) is a chemotherapeutic agent with well established effects on cell growth arrest and apoptosis. In this study, we investigated the potential roles of bioactive sphingolipids in mediating the growth suppressing effects of GMZ on a polyoma middle T transformed murine endothelial cell line. After 12-hour GMZ (0.6 μM) treatment, cell growth was arrested at the G₀/G₁ phase as detected by flow cytometric cell cycle analysis and MTT cell viability analysis, and this was accompanied by dephosphorylation of the retinoblastoma protein (Rb). Furthermore, GMZ treatment resulted in increased levels of specifically the very long chain ceramides as determined by mass spectrometry. Mechanistically, GMZ did not appear to affect the activities of many enzymes of ceramide metabolism; however, GMZ caused a selective reduction in the protein levels of neutral ceramidase (NCDase), as indicated by Western blot analysis, with a concomitant decrease in NCDase activity. The significance of NCDase loss on cell cycle regulation was investigated by specific knockdown of the enzyme using small interfering RNA (siRNA). Interestingly, NCDase siRNA transfection was sufficient to induce a cell cycle arrest at G₀/G₁ and an increase in total ceramide levels, with significant elevation in very long chain ceramides (C_24:1 and C_24:0). NCDase siRNA also induced Rb dephosphorylation. These data provide evidence for a novel mechanism of action for GMZ and highlight downregulation of NCDase as a critical step in GMZ-mediated ceramide elevation and cell cycle arrest.