Zinc Sensitizes Lung Cancer Cells to Anoikis through Down-Regulation of Akt and Caveolin-1.

Anoikis is a particular type of apoptosis induced by the loss of cell attachment from extracellular matrix. It has been shown to play a critical role in the inhibition of cancer metastasis. Herein, we report for the first time that zinc, an essential trace element, has anoikis sensitizing activity against lung cancer cells. An anoikis assay showed that zinc treatment at the concentrations of 0-50 µM enhanced the anoikis response in human lung cancer H460 cells with significant decreased cell viability and increased number of apoptosis cells detected with Hoechst 33342 and PI co-staining assay. Moreover, zinc significantly inhibited the growth of cancer cells in an anchorage-independent condition. This is mediated through the zinc-induced decrease in prosurvival active protein kinase B (Akt) and metastasis-regulating caveolin-1 (Cav-1) protein expression. Taken together, our results indicate that zinc sensitizes non-small cell lung cancer cells to anoikis and may play a role in the prevention of cancer metastasis.

Effects of Fructo-Oligosaccharide Supplementation on Constipation in Elderly Continuous Ambulatory Peritoneal Dialysis Patients.

UNLABELLED: ♦ BACKGROUND: Fructo-oligosaccharides (FOS) exhibit soluble-fiber properties that beneficially affect bowel function and relieve constipation. The effects of FOS supplementation on constipation and biochemical parameters were examined in elderly continuous ambulatory peritoneal dialysis (CAPD) patients. ♦ METHODS: This randomized, double-blind, placebo-controlled, cross-over study was performed in elderly CAPD patients (5 males and 4 females) with chronic constipation. All subjects were randomly assigned to receive either 20 g FOS or placebo daily for 30 days. After a 14-day washout period, the patients were switched to the other substance for 1 more month. Before and after each treatment period, frequency of defecation, characteristics of feces, and colonic transit were evaluated. Biochemical parameters were also assessed. ♦ RESULTS: Fructo-oligosaccharides significantly increased the frequency of defecation (10.5 ± 2.0 vs 6.2 ± 1.4 times per week, p < 0.005) and changed the feces' appearance from type 1 (nut-like) to type 4 (sausage-like). The colonic transit determined by geometric center (GC) was augmented after FOS supplementation (3.9 ± 0.3 vs 3.2 ± 0.4, p < 0.05). Fructo-oligosaccharides had no effects on biochemical parameters. Fructo-oligosaccharides caused mild discomforts which were well tolerated after dose adjustment. ♦ CONCLUSIONS: Fructo-oligosaccharide supplementation is effective, well tolerated, and can be an alternative to other laxatives in CAPD patients with constipation. Further studies are needed to better assess the biochemical effects of FOS in the chronic kidney disease population.

Zinc supplementation improves anticancer activity of monocytes in type-2 diabetic patients with metabolic syndrome.

BACKGROUND: Transmembrane tumor necrosis factor (TNF)-α, found on monocytes, is a body's key defense against cancer. In patients with type 2 diabetes mellitus (DM) and metabolic syndrome, immunity is suppressed, resulting in a high risk of several inflammatory disorders and cancer. PATIENTS AND METHODS: Seventeen patients with type 2 DM and metabolic syndrome were supplemented with either 30 mg of elemental zinc/day or placebo for eight weeks. Transmembrane TNF-α-expressing monocytes and lymphocytes, and plasma TNF-α levels were analyzed before and after supplementation. RESULTS: The present study revealed that zinc supplementation significantly increased the proportion of monocytes expressing transmembrane TNF-α. While the plasma TNF-α levels and TNF-α expressing lymphocytes were not significantly altered in the zinc-treated and placebo groups, higher proportion of TNF-α bound monocytes were observed in the zinc-treated group. CONCLUSION: Because functional transmembrane TNF-α was shown to be implicated in defense mechanisms, these findings suggest that zinc supplementation may benefit immune response against cancer in patients with DM and metabolic syndrome.

Development of diabetes telephone-linked care system for self-management support and acceptability test among type 2 diabetic patients.

OBJECTIVE: Develop the diabetes telephone-linked care system for self-management support and test acceptability in terms of system uses, satisfaction and perception of easiness, helpfulness, and emotion with the system. MATERIAL AND METHOD: The automated telephone system with diabetes knowledge interactive voice response (IVR) subsystem was developed to provide diversified curriculum arrangement including general knowledge module (Knowledge IVR, suggestive segment module (Suggestive IVR) and 10 QA sets for assessment with tailored information feedback (QA IVR). The system could deliver 1,120 messages over five weeks among 112 intervened participants of the on-going randomized controlled trial on its impact on glycemic control. The system analyzed the level of completed responses. RESULTS: Overall, 25.9% of the responses were intermittent, 46.4% had consistent adherences, 14.3% were poor responses, and 13.4% were non-responses. The total time use of the system, among 97/112 participants, was 6,189 minutes (mean 63.80, SD 26 63). The degree of call completeness did not vary according to the participant's socio-economic status, glycemic level, or years of diabetes diagnosis. The satisfaction of participants to the program was done by interviewed by telephone among 95 of 112 participants. Most study participants reported that they were very/moderately satisfied with the program (89.5%) regarding its usefulness and helpfulness on awareness, understanding and reminding behavior change attempts. In all, 95.8% of the responders planned to participate in the next program. Duration of time uses of the TLC was significantly correlated to the total scores of helpfulness and of emotion (p < 0.01; r = 0.38 and 0.31 respectively). CONCLUSION: This prototype of diabetes telephone-linked care for Thai diabetes is a step forward in response to diabetes self-management education need. Further studies are needed about its efficacies on diabetes self-management improvement and glycemic control, as well as its cost-effectiveness.

Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients.

OBJECTIVES: To determine whether a low fat diet supplemented with omega-3 positively affects quality of life (QOL) in relapsing-remitting MS (RRMS) patients. In this 1-year long double-blind, randomized trial, patients were randomized to two dietary interventions: the "Fish Oil" (FO) group received a low fat diet (15% fat) with omega-3 FOs and the "Olive Oil" (OO) group received the AHA Step I diet (fat 30%) with OO supplements. The primary outcome measure was the Physical Components Summary Scale (PCS) of the Short Health Status Questionnaire (SF-36). Additional measures using MS specific QOL questionnaires, neurological status and relapse rate were obtained. RESULTS: 31 RRMS patients were enrolled, with mean follow up over 11 +/- SD 2.9 months. Clinical benefits favoring the FO group were observed on PCS/SF-36 (P = 0.050) and MHI (P = 0.050) at 6 months. Reduced fatigue was seen on the OO diet at 6 months (P = 0.035). The relapse rate decreased in both groups relative to the rates during the 1 year preceding the study: mean change in relapse rate in the FO group: -0.79 +/- SD 1.12 relapses/year (P = 0.021) vs. -0.69 +/- SD 1.11 (P = 0.044) in the OO group. This study suggests that a low fat diet supplemented with omega-3 PUFA can have moderate benefits in RRMS patients on concurrent disease modifying therapies.

Effect of dietary fat intake and exercise on inflammatory mediators of the immune system in sedentary men and women.

OBJECTIVE: Dietary fat intake and exercise affect the immune system. This study determined the changes in inflammatory components of the immune system in response to maximal exercise with three levels of dietary fat intake: 19%, 30%, and 50% of total calories. METHODS: Five men and six women were randomly assigned to consume diets with 19% and 50% calories from fat for three weeks each, with a one-week washout. The habitual and washout diets were 30% calories from fat. At the beginning and the end of each diet, body composition and maximal exercise tests were performed. Blood samples were collected before and after exercise to determine the immunological parameters. RESULTS: The subject's energy intake was balanced to expenditure on the 30% and 50% diets, but was in negative balance on the 19% diet. Exercise led to significant increases in the concentrations of leukocytes, neutrophils, lymphocytes, monocytes, plasma tumour necrosis factor (TNF)-alpha, plasma interleukin (IL)-2, plasma soluble vascular cell adhesion molecule (sVCAM)-1, and the production of IL-1beta and IL-6 by peripheral blood mononuclear (PBMN) cells stimulated with lipopolysaccharide (LPS), irrespective of diets (p < 0.05). The 19% fat diet resulted in increased plasma soluble intercellular adhesion molecule (sICAM)-1 after exercise. Leukotriene (LT) B4 concentration released by neutrophils stimulated with LPS was higher in the 50% fat diet, compared to the lower fat diets, and the sICAM-1 production of neutrophils stimulated with LPS was significantly increased after exercise only with 30% fat diet. CONCLUSION: While a short, intense bout of exercise increased pro-inflammatory mediators of the immune system, decreasing fat intake to 19% on a caloric deficient diet caused a greater increase in plasma TNF-alpha, sVCAM-1 and sICAM-1 concentration than the 30% and 50% fat diets in male and female subjects. Increasing fat calories to 50% with caloric balance did not exacerbate pro-inflammatory mediators compared to a 30% fat diet.

Effect of low and high fat diets on nutrient intakes and selected cardiovascular risk factors in sedentary men and women.

OBJECTIVE: The desired level of dietary fat intake is controversial. The effect of decreasing fat intake to 19% and increasing it to 50% from a control diet of 30% on nutritional status and cardiovascular risk factors in healthy individuals was studied. METHODS: Eleven healthy subjects (5 men and 6 women) were randomized to consume diets with 19% and 50% calories from fat. Each diet lasted 3 weeks, with a one-week washout. The habitual and washout diets were determined to be 30% fat. At the beginning and the end of each diet, fasting blood was collected to determine plasma lipoproteins, and physiological factors were measured. RESULTS: Total caloric expenditure was similarly balanced to intake on the 30% and 50% fat diets, but intake was significantly lower on the 19% fat diet and led to a loss of 0.6 kg body weight. Consumptions of essential fatty acids, vitamin E and zinc were improved with increased fat intake, but folate intake was compromised on the 30% and 50% fat diets. Compared with the 50% fat diet, subjects consuming the 19% fat diet had significantly lower HDL cholesterol (HDL-C) (54 +/- 3 vs. 63 +/- 3 mg. dL(-1), p < 0.05) and apolipoprotein A1 (ApoA1) (118 +/- 4 vs. 127 +/- 3 mg/dL, p < 0.05). Changing the levels of fat intake did not affect % body fat, heart rate, blood pressure, blood triglycerides, total cholesterol (TC), LDL cholesterol, apolipoprotein B (ApoB), TC/HDL-C and ApoA1/ApoB ratios. CONCLUSION: A low fat diet (19%) may not provide sufficient calories, essential fatty acids, and some micronutrients (especially vitamin E and zinc) for healthy untrained individuals, and it also lowered ApoA1 and HDL-C. Increasing fat intake to 50% of calories improved nutritional status, and did not negatively affect certain cardiovascular risk factors.

Effects of dietary omega3 and omega6 lipids and vitamin E on chemokine levels in autoimmune-prone MRL/MpJ-lpr/lpr mice.

Elevated levels of chemokines, such as Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES), Monocyte Chemotactic Protein-1 (MCP-1), Macrophage Inflammatory Protein-1alpha (MIP-1alpha), and Macrophage Inflammatory Protein-1beta (MIP-1beta) have been found in rheumatoid arthritis (RA) and juvenile arthritis (JA), and they may be associated with the pathogenesis of these diseases. These chemokines are implicated in the migration of specific leukocytes into the joints. Omega-3 (omega3) fatty acid rich-fish oil (FO) and vitamin E may delay the progress of certain autoimmune diseases. The present study was designed to understand the effects of dietary lipids (omega-6 and omega-3 fatty acids) and vitamin E on the production of chemokines in autoimmune-prone MRL/lpr (a mouse model for RA) and congenic control MRL/++ mice. The MRL mice were fed for 4.5 months omega-6 and omega-3 diets that varied in lipid sources (corn oil; CO and fish oil; FO) and vitamin E levels (269 I.U./kg and 694 I.U./kg diet). Spleen cells were isolated and cultured aseptically in the presence of PHA for 48 h at 37 degrees C and the levels of chemokines (RANTES, JE/MCP-1 and MIP-1alpha) were determined in the cell-free supernatants. The levels of RANTES and JE/MCP-1 were significantly higher in MRL/lpr mice compared to MRL/++ mice. The FO had differential effect on RANTES and MCP-1 production by spleen cells. The production of RANTES and JE/MCP-1 by spleen cells in mice fed the FO diets was significantly lower than in mice fed the CO diets (p < 0.0001). The levels of vitamin E did not affect the production of RANTES and JE/MCP-1. The levels of vitamin E had a significant effect on MIP-1alpha as the spleen cells of mice fed diets containing 694 IU/kg diet of vitamin E produced significantly higher levels of MIP-1alpha compared to the group of mice fed the diets containing 269 IU of vitamin E (p < 0.0001). The data obtained from this study in MRL/lpr and MRL/++ mice suggest that FO diets containing omega-3 fatty acids are beneficial in decreasing the levels of certain pro-inflammatory chemokines (RANTES and MCP-1) thereby delaying the onset of and severity of autoimmune symptoms in MRL/lpr mouse model.