Combination of polyglycerol sebacate coated with collagen for vascular engineering.

Introduction: Here, we monitored the cytocompatibility of scaffolds consisting of poly (glycerol sebacate) (PGS) coated with collagen (Col) for endothelial cell activity after 72 hours. Methods: Human endothelial cells were allocated into Control, PGS, and PGS+Col groups. Scaffolds were characterized using FTIR and HNMR spectroscopy. Contact angel analysis and SEM were used to study wettability, surface morphology, and cell attachment. Cell survival was assessed using LDH leakage assay. Levels of Tie-1, Tie-2, VE-Cadherin, and VEGFR-2 were measured using western blotting and real-time PCR. Results: FTIR and HNMR analyses revealed the proper blending in PGS+Col group. SEM imaging exhibited a flat surface in the PGS group while thin Col fibers were detected in PGS+Col surface. The addition of Col to the PGS reduced the contract angle values from 97.3˚ to 81.1˚. Compared to PGS substrate alone, in PGS+Col group, cells appropriately attached to the surface. PGS and PGS+Col did not alter the leakage of LDH to the supernatant compared to control cells, showing the cytocopatiblity of PGS-based scaffolds. SOD and NO levels were increased significantly in PGS (p<0.05) and PGS+Col groups (p<0.001), respectively. We found that PGS+Col decreased Tie-1 content in endothelial cells whereas protein levels of Tie-2 and VE-Cadherin and expression of VEGFR-2 remained unchanged compared to PGS and control groups. Conclusion: Simultaneous application of Col and PGS can stimulate normal endothleial cell morphology without the alteration of tyrosine kinases receptors and cadherin.

Effect of docosahexaenoic acid plus insulin on atherosclerotic human endothelial cells.

BACKGROUND: Atherosclerosis is touted as one of the most critical consequences of diabetes mellitus indicated by local inflammation of endothelial cells. The Effect of Omega 3 fatty acids, mainly docosahexaenoic acid (DHA), has been investigated in cells after exposure to high doses of lipids. The current experiment aimed to address the modulatory effects of docosahexaenoic acid and insulin in palmitic-treated human endothelial cells. METHODS: Human umbilical vein endothelial cells were treated with 1 mM palmitic acid, 50 µM insulin, 50 µM docosahexaenoic acid, and their combination for 48 h. Cell survival rate and apoptosis were measured using MTT and flow cytometry assays. The Griess assay detected NO levels. Protein levels of TNF-α, IL-6, and NF-κB were studied using ELISA and immunofluorescence imaging. The expression of genes participating in atherosclerosis was monitored using PCR array analysis. RESULTS: Oil Red O staining showed the inhibitory effect of DHA and insulin to reduce the intracellular accumulation of palmitic acid. Both DHA and Insulin blunted palmitic acid detrimental effects on HUVECs indicated by an increased survival rate (p < 0.05). The percent of apoptotic cells was decreased in palmitic-treated cells received insulin and DHA compared to palmitic-treated group (p < 0.05). Based on our data, DHA and Insulin diminished the production of all inflammatory cytokines, TNF-α, IL-6, and NF-κB, in palmitic-treated cells (p < 0.05). Similar to these data, NO production was also decreased in all groups treated with insulin and DHA compared to the palmitic-treated cells (p < 0.05). PCR array analysis revealed the modulatory effect of DHA and insulin on the expression of atherosclerosis-related genes pre-treated with palmitic acid compared to the control group (p < 0.05). CONCLUSION: DHA and Insulin could alter the dynamic growth and dysfunctional activity of human endothelial cells after treatment with palmitic acid. Taken together, Omega 3 fatty acids, along with insulin, could dictate specific cell behavior in endothelial cells in vitro.

Effects of cholecalciferol supplementation on serum angiogenic biomarkers in breast cancer patients treated with tamoxifen: A controlled randomized clinical trial.

OBJECTIVE: The aim of this study was to investigate the effects of cholecalciferol supplementation on serum levels of angiogenic parameters in patients with breast cancer (BC) who were treated with tamoxifen. METHODS: This was a pilot-based, randomized, triple-blind, placebo-controlled clinical trial with 52 patients with BC randomly assigned to either an intervention group receiving weekly 50 000 IU cholecalciferol or a placebo group for 8 wk. At baseline and at end of study, serum levels of angiogenic growth factors such as vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang)-2, hypoxia-inducible factor (Hif)-1, and high-sensitivity C-reactive protein were measured by enzyme-linked immunosorbent assay. Every 4 wk, a completed 3-d, 24-h dietary record and daily sunlight exposure checklist were collected and anthropometric variables were measured. RESULTS: The ultimate number of participants in each arm was 22 for analyses. For premenopausal women, cholecalciferol supplementation resulted in a significant decrease in serum levels of Ang-2 and VEGF-A after 8 wk of treatment (P < 0.05). In the absence of vascular invasion, supplementation led to a significant decrease in Ang-2 levels compared with the placebo group (P < 0.05). Supplementation caused significant increases in Hif-1 in patients diagnosed with the infiltration of tumors into vascular or lymphatic vessels (P < 0.05). CONCLUSION: Cholecalciferol supplementation achieved sufficient efficacy among patients with BC taking tamoxifen and could be effective in the reduction of angiogenic biomarkers particularly dependent on the infiltration status of the tumor to vessels. Further studies with larger subgroups should be investigated.

Enzymatic Antioxidant and Lipid Peroxidation Evaluation in the Newly Diagnosed Breast Cancer Patients in Iran

Background: Breast cancer is caused by breast tissue malignant cells and it has become one of the main medical concerns with a socio-economic significance especially for women. Among the multiple factors involved in the initiation, progression, and invasion of breast cancer, oxidative stress plays an important role. Antioxidant status, lipid peroxidation, and oxidative stress in newly diagnosed breast cancer patients were determined to find a defined pattern of oxidative stress in these patients. Methods: The malondialdehyde (MDA) levels (as an indicator of lipid peroxidation), glutathione peroxidase (GPX), and superoxide dismutase (SOD) activities of newly diagnosed breast cancer patients (n=38) and controls (n=38) were assessed using blood samples. Results: MDA level and SOD activity were significantly higher in the breast cancer patients compared to the healthy subjects group (p<0.05). Compared to the healthy group, GPX activity decreased significantly in patients group (p<0.05). Conclusions: High lipid peroxidation is an important risk factor for breast cancer and the increased levels of superoxide anion in breast cancer cells may be a reason for the induction of SOD activity. Nevertheless, oxidative stress is an important factor in development and progression of breast cancer. Further studies on it can lead to a more helpful approach to management of breast cancer.

Effects of Eicosapentaenoic Acid Supplementation on Lipid and Lipoprotein Profile in Hypertriglyceridemic Subjects with Different Proliferator-activated Receptor Alpha Genotypes.

BACKGROUND: We determined the blood lipid-lowering effects of eicosapentaenoic acid (EPA) on hypertriglyceridemic subjects with Leu162/Val in exon 5 and G/C in intron7 polymorphism of peroxisome proliferator-activated receptor alpha (PPARα)genotypes that, to our knowledge, have not been previously studied. METHODS: A total of 170 hypertriglyceridemic subjects were enrolled and genotyped for Ala54Thr, Leu162Val, and intron7 polymorphism by the use of a polymerase chain reaction-restriction fragment length polymorphism method. After determination of their genotypes, the first 23 eligible subjects who were found as Ala54 carriers and the first 23 eligible Thr54 carriers were enrolled in the study and stratified for PPARα genotypes. Participants took 2 g of pure EPA daily for 8 weeks. Fasting blood lipid and lipoprotein profiles were determined and changes from baseline were measured. RESULTS: We observed significant difference between EPA supplementation and Leu162 and Val162, Interon 7 (GG and GC) carriers (P < 0.001). We did not observe significant associations between the PPARα L162V single nucleotide polymorphism and multiple lipid and lipoprotein measures. Although EPA consumption lowered lipid and lipoprotein concentrations in Leu162 and Val162 carriers and Interon 7 CC and GC carriers, these differences between the studied groups were not statistically significant. CONCLUSIONS: EPA consumption has a lipid-lowering effect in hypertriglyceridemic subjects in both Leu162 and Val162 carriers. But there was no significant interaction between EPA supplementation and PPARα genotypes. Thus, genetic variation within the PPARα Leu162/Val cannot modulate the association of EPA intakes with lipid and lipoprotein profile. However, we must note that the sample size in this study was small.

Effects of EPA supplementation on plasma fatty acids composition in hypertriglyceridemic subjects with FABP2 and PPARα genotypes.

BACKGROUND: Fatty acid binding protein 2 (FABP2) and peroxisome proliferator-activated receptor α (PPARα) are involved in cellular uptake and metabolism of fatty acids. Polymorphism of FABP2 and PPARα may influence plasma levels of fatty acids in those who take supplemental eicosapentaenoic acid (EPA). The purpose of this study was to study the potential associations between the Ala54/Thr polymorphism in FABP2 protein and the Leu162/Val in exon 5 and G/C in intron 7 of PPARα with plasma fatty acids composition after EPA supplementation. METHODS: Twenty three FABP2 Ala54 and twenty three Thr54 carriers with hypertriglyceridemia were enrolled in this study. Participants took 2 g of pure EPA daily for 8 wks. Plasma fatty acids composition was determined and changes from the baseline were measured. RESULTS: Although EPA supplementation increased the level of plasma EPA and ω-3 fatty acids in both carriers of FABP2 and PPARα genes, these effects were more pronounced in Thr54 and Val162 carriers. EPA supplementation decreased the level of some n-6 fatty acids such as arachidonic acid. CONCLUSION: EPA consumption has more favorable effects on blood n-3 fatty acids and can change the level of plasma n-3 fatty acids, particularly EPA. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for preventing cardiovascular diseases. Finally, diets and micronutrient recommendations should be individualized for high risk people.

Effects of Parsley (Petroselinum crispum) and its Flavonol Constituents, Kaempferol and Quercetin, on Serum Uric Acid Levels, Biomarkers of Oxidative Stress and Liver Xanthine Oxidoreductase Aactivity inOxonate-Induced Hyperuricemic Rats.

Increased serum uric acid is known to be a major risk related to the development of several oxidative stress diseases. The aim of this study was to investigate the effect of parsley, quercetin and kaempferol on serum uric acid levels, liver xanthine oxidoreductase activity and two non-invasive biomarkers of oxidative stress (total antioxidant capacity and malondialdehyde concentration) in normal and oxonate-induced hyperuricemic rats. A total of 60 male Wistar rats were randomly divided into ten equal groups; including 5 normal groups (vehicle, parsley, quercetin, kaempferol and allopurinol) and 5 hyperuricemic groups (vehicle, parsley, quercetin, kaempferol and allopurinol). Parsley (5 g/Kg), quercetin (5 mg/Kg), kaempferol (5 mg/Kg) and allopurinol (5 mg/Kg) were administrated to the corresponding groups by oral gavage once a day for 2 weeks. The results showed that parsley and its flavonol did not cause any significant reduction in the serum uric acid levels in normal rats, but significantly reduced the serum uric acid levels of hyperuricemic rats in a time-dependent manner. All treatments significantly inhibited liver xanthine oxidoreductase activity. Parsley, kaempferol and quercetin treatment led also to a significant increase in total antioxidant capacity and decrease in malondialdehyde concentration in hyperuricemic rats. Although the hypouricemic effect of allopurinol was much higher than that of parsley and its flavonol constituents, it could not significantly change oxidative stress biomarkers. These features of parsley and its flavonols make them as a possible alternative for allopurinol, or at least in combination therapy to minimize the side effects of allopurinol to treat hyperuricemia and oxidative stress diseases.

Fatty acid-binding protein-2 genotype influences lipid and lipoprotein response to eicosapentaenoic acid supplementation in hypertriglyceridemic subjects.

OBJECTIVE: The blood lipid-lowering effects of eicosapentaenoic acid (EPA) on hypertriglyceridemic subjects with different fatty acid-binding protein-2 (FABP2) genotypes have not, to our knowledge, been previously studied. METHODS: Twenty-three FABP2 Ala54 and 23 Thr54 carriers with hypertriglyceridemia (triacylglycerol level >200mg/dL) were enrolled in this study. Participants took 2g of pure EPA daily for 8 wk. Fasting blood lipid and lipoprotein profiles were determined and changes from baseline were measured. RESULTS: Blood lipids and lipoprotein responses of the FABP2 genotypes differed after EPA supplementation. Changes from baseline for triacylglycerol (19.2% decrease for Ala54 and 60.5% for Thr54, P<0.001), very low-density lipoprotein (20.0% decrease for Ala54 and 60.5% for Thr54, P<0.001), apolipoprotein CIII (22.8% decrease for Ala54 and 36.4% for Thr54, P<0.01), and high-density lipoprotein cholesterol (17.6% increase for Ala54 and 30.7% for Thr54, P<0.01) differed significantly between the two carrier groups. However, changes in total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B were not significant. EPA supplementation increased plasma EPA in Ala54 and Thr54 carriers. Although EPA supplementation increased the level of plasma EPA in both carrier groups, this effect was more pronounced in the Thr54 carriers. CONCLUSION: Therefore, EPA consumption has more favorable effects on blood lipids of hypertriglyceridemics with Thr54 genotype rather than those with Ala54. The level of plasma EPA increases after EPA supplementation. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for reducing blood triacylglycerol concentration.

Association between the FABP2 Ala54Thr, PPARα Leu162/Val, and PPARα intron7 polymorphisms and blood lipids ApoB and ApoCIII in hypertriglyceridemic subjects in Tehran.

BACKGROUND: The alanine to threonine substitution at codon 54 in the FABP2 gene and PPARα Val162 allele have been associated with hypertriglyceridemia. OBJECTIVE: We sought to determine the prevalence of the Ala54Thr polymorphism of fatty acid binding protein (FABP) 2 gene and the Leu162/Val in exon 5 and G/C in intron7 polymorphism of peroxisome proliferator-activated receptor alpha (PPARα) gene in hypertriglyceridemic patients and their associations with blood lipid concentrations. METHODS: A total of 170 hypertriglyceridemic subjects were enrolled and genotyped for Ala54Thr, Leu162Val, and intron 7 polymorphism by the use of a polymerase chain reaction-restriction fragment length polymorphism method. Fasting blood triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein (Apo)B, and ApoCIII also were determined. RESULTS: We found frequency of 81.2% for the Thr54 polymorphism among hypertriglyceridemic subjects. Positive associations were observed between this polymorphism and greater blood triglyceride, very low-density lipoprotein, and ApoCIII levels and lower blood high-density lipoprotein cholesterol concentration both in men and women. However, no association was found between the Thr54 polymorphism and TC, low-density lipoprotein cholesterol, ApoB, and body mass index. Frequency of the Leu162Val polymorphism was 21.8%. The Leu162Val polymorphism was not associated with lipid and lipoprotein concentrations in hypertriglyceridemic subjects (both in men and women). The frequency of intron7 polymorphism was 55.3% in subjects studied and, except for body mass index and TC, no association was found between the intron7 allele and blood lipids ApoB, and ApoCIII. CONCLUSION: Frequency of the Thr54 polymorphism is high in hypertriglyceridemic subjects, and the presence of this allele may increase some blood lipid and lipoprotein concentrations. In addition, the frequency of intron7 polymorphism may be greater than Leu162Val in hypertriglyceridemic patients.

Effects of onion on serum uric acid levels and hepatic xanthine dehydrogenase/xanthine oxidase activities in hyperuricemic rats.

The aim of this study was to investigate the effects of onion on serum uric acid levels and hepatic Xanthine Dehydrogenase/Xanthine Oxidase activities in normal and hyperuricemic rats. Hyperuricemia was induced by intraperitoneal injection of 250 mg kg(-1) potassium oxonate in rats. Oral administration of onion at 3.5 and 7.0 mg kg(-1) day(-1) for 7 days was able to reduce serum uric acid levels in hyperuricemic rats with no significant effects on the level of this compound in the normal animals. In addition, onion when tested in vivo on rat liver homogeneities elicited significant inhibitory actions on the Xanthine Dehydrogenase (XDH) and Xanthine Oxidase (XO) activities. This effect resulted less potent than that of allopurinol. However, the hypouricemic effect observed in the experimental animal did not seem to parallel the change in XDH and XO activities, implying that the onion might be acting via other mechanisms apart from simple inhibition of enzyme activities. Such hypouricemic action and enzyme inhibitory activity of onion makes it a possible alternative for allopurinol, or at least in combination therapy to minimize the side-effects of allopurinol, in particular in long-term application.

Development and validation of a short food-frequency questionnaire for screening women of childbearing age for vitamin A status in northwestern Iran.

A high percentage of women in their childbearing years suffer from subclinical vitamin A deficiency; 10% to 20% of pregnant women worldwide are vitamin A deficient. This study aimed to design and validate a short food-frequency questionnaire to serve as a simple screening tool for vitamin A status in women of childbearing age. The sample consisted of 187 healthy, nonpregnant, nonlactating women 15 to 49 years of age, from urban and rural areas of Marand district in East Azerbaijan. Dietary intake was evaluated by a face-to-face interview using a 24-hour dietary recall for two consecutive days and a 41-item qualitative food frequency questionnaire. Height, weight, and serum retinol were measured. Serum retinol values were less than 20 micrograms/dl for three subjects, while an additional 34 subjects (18%) had values between 21 and 30 micrograms/dl. Principal-component analysis performed on the food-frequency questionnaire identified five components that together defined 34.4% of the variance in estimated vitamin A intake and were used to derive a 20-item short food-frequency questionnaire. Internal consistency of the short instrument was acceptable (Cronbach's alpha = .59). Serum retinol was significantly correlated with total vitamin A intake and with intake of vitamin A from plant sources, as estimated by the short food-frequency questionnaire. Important sources of provitamin A in these women's diets included some not typical of other populations: nuts and green leaves of types used elsewhere in small quantities as herbs, but important in Iran because the amount and frequency of consumption are relatively high. We conclude that the questionnaire is relatively valid and potentially useful in identifying women at risk for vitamin A deficiency in this population.