A placebo controlled randomized clinical trial of Crocus sativus L. (saffron) on depression and food craving among overweight women with mild to moderate depression.

WHAT IS KNOWN AND OBJECTIVE: Crocus sativus L., commonly known as saffron, has known anti-depressive properties. However, its effects on food craving and body weight in depressed patients are unknown. Hence, we aimed to evaluate the effects of saffron capsules on food craving, body weight and depression among overweight women with mild and moderate depression compared to the placebo. METHODS: Seventy-three women with BMI ≥ 25 comorbid with mild-to-moderate depression were recruited in this 12-week double-blind, placebo-controlled randomized clinical trial. Participants were randomly assigned into one of the two groups receiving daily either 30 mg of Crocus sativus capsules (15 mg twice/day) or placebo capsules (twice/day). We performed body composition assessments, and beck depression inventory-II at the baseline, and then 2, 4, 8 and 12 weeks later. One month after the participants stopped taking the capsules, weight differences were measured and compared between groups. RESULTS AND DISCUSSION: Fifty-two patients finished the study. The demographic and clinical variables at baseline were the same in two groups. Mean depression scores in the saffron group significantly decreased compared to placebo (mean ± SD: -8.4 score ± 5.9 vs -3.9 ± 5.5; t[50] = 2; P = .007; 95% CI: 1.3-7.7). There was not a significant effect of saffron on food craving using repeated-measures ANOVA, F(1, 29) = 0.38, P = .54. Patients in the saffron group showed fewer side effects. WHAT IS NEW AND CONCLUSION: Saffron capsules were not effective in reducing food craving, but as a safe over-the-counter supplement, it may help reduce the symptoms of depression in patients who experience mild or moderate depression and are overweight.

Vitamin D downregulates key genes of diabetes complications in cardiomyocyte.

OBJECTIVE: Vitamin D deficiency has been reported to be associated with the incidence of type 1 and type 2 diabetes and worsening of diabetes complications. This study was designed to investigate the effect of vitamin D treatment on the expression of five key genes involved in the development of diabetic cardiomyopathy. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups. The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin (STZ) to develop diabetes. Then groups were treated for 4 weeks either with placebo or vitamin D (two injections of 20,000 IU/kg). Serum levels of glucose, insulin, HbA1c, and advanced glycation end products (AGEs), as well as the gene expression of AGE cellular receptor (RAGE), glyoxalase, aldose reductase, O-GlcNAc transferase (OGT), and glutamine-fructose-6-phosphate aminotransferase (GFAT) and nuclear factor-kB (NF-kB) activity of nuclear extracts were assessed at the end of experiment. RESULTS: Increment in serum cholecalciferol could improve hyperglycaemia and hypoinsulinemia in diabetic rats. In addition, a significant reduction was observed in RAGE, OGT, and GFAT gene expression and NF-kB activity in cardiac myocytes. CONCLUSIONS: Vitamin D might contribute in reducing diabetic cardiomyopathy not only by improving blood glucose and insulin levels but also via downregulating AGE and hexosamine pathways and decreasing NF-kB activity in heart tissue.

Health-related quality of life and medication adherence in elderly patients with epilepsy.

OBJECTIVE: Considering the high prevalence of epilepsy in the elderly and the importance of maximising their quality of life (QoL), this study aimed to investigate the relationship between medication adherence and QoL, and the mediating effects of medication adherence on the association between serum antiepileptic drug (AED) level and seizure severity with QoL in elderly epileptics. METHODS: In a longitudinal study, 766 elderly patients with epilepsy who were prescribed a minimum of one antiepileptic drug were selected by convenience sampling method. A Medication Adherence Report Scale (MARS-5) questionnaire was completed at the baseline. Seizure severity and QoL were assessed after six months using the Liverpool Seizure Severity Scale (LSSS) and the QoL in Epilepsy (QOLIE-31) questionnaires respectively. Serum level of AED was also measured at six-month follow-up. RESULTS: Medication adherence was significantly correlated with both seizure severity (ß = -0.33, p < 0.0001) and serum AED level (ß = 0.29, p < 0.0001) after adjusting for demographic and clinical characteristics. Neither QoL nor its sub-classes were correlated with seizure severity. In addition, a significant correlation was not observed between serum AED level and QoL. However, medication adherence was significantly correlated with QoL (ß = 0.30, p < 0.0001). The mediating effects of medication adherence on the association between serum AED level (Z = 3.39, p < 0.001) and seizure severity (Z = -3.47, p < 0.001) with QoL were supported by the Sobel test. CONCLUSION: This study demonstrates that medication adherence has a beneficial impact on QoL in elderly epileptics. Therefore, adherence to treatment should be monitored to improve their QoL.

Development of a new live attenuated Leishmania major p27 gene knockout: Safety and immunogenicity evaluation in BALB/c mice.

Genetically modifying Leishmania major by eliminating essential virulence genes have been proposed as potential vaccine candidates. p27 is a COX component that is responsible for ATP synthesis. In this study a new mutant of Leishmania major (L. major) (MRHO/IR/75/ER) lacking the p27 gene (Lmp27-/-) was produced via homologous recombination, marking the first time such a strain has been developed. In vitro macrophage infectivity and In vivo safety, and overall immunogenicity were evaluated at various time periods following inoculation into BALB/c mice. Skin lesion development, parasite burden in the liver and spleen, cytokine and antibody levels, splenocyte proliferation, and delayed type hypersensitivity (DTH) were the measured variables. Results demonstrated that the Lmp27-/- mutant caused no skin lesion, had low parasitic burdens in the liver and spleen, and had a significantly increased Th1 response. These results suggest that the Lmp27-/- mutant has the potential to be evaluated as a vaccine candidate.

The effect of 1, 25(OH)2 D3 (calcitriol) alone and in combination with all-trans retinoic acid on ROR-γt, IL-17, TGF-ß, and FOXP3 gene expression in experimental autoimmune encephalomyelitis.

OBJECTIVES: It has been shown that calcitriol and all-trans retinoic acid (ATRA) have modulatory effects on the immune system. The present study investigates the synergistic effects of combination treatment of calcitriol and ATRA in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). METHODS: The mice were allocated to four preventive groups, each consisting of eight animals, ATRA (250 µg/mouse), calcitriol (100 ng/mouse), combination of ATRA and calcitriol (125  µg/mouse and 50 ng/mouse) and vehicle groups. EAE was induced by MOG35-55 peptide in female C57BL/6 mice. Treatments were initiated at day 1 before immunization and continued every other day throughout the study until the day 21 post-immunization. Splenocytes were isolated from EAE-induced mice and the expression of retinoic acid receptor-related orphan receptor gamma t (ROR-γt), Interleukin-17 (IL-17), transforming growth factor beta (TGF-ß), and forkhead box P3 (FOXP3) genes was measured using real-time polymerase chain reaction. RESULTS: The expression of FOXP3 and TGF-ß genes in the splenocytes of combination-treated and calcitriol alone-treated mice was significantly increased compared to vehicle group (P < 0.05). The expression of ROR-γt and IL-17 genes in the splenocytes of ATRA, calcitriol and combination- treated mice was significantly reduced compared to those of vehicle- treated mice (P < 0.05). The relative expression level of ROR-γt was significantly (P < 0.05) lower in the combination group than in the mice treated by ATRA or calcitriol alone. DISCUSSION: This study demonstrated that treatment with combination of calcitriol and ATRA can be considered as a new strategy for MS prevention and treatment.

Association between uncoupling protein 2, adiponectin and resting energy expenditure in obese women with normal and low resting energy expenditure.

Obesity is recognized as the most prevalent metabolic disease worldwide. Decreases in energy expenditure may increase risk of obesity. One of the key regulators of energy balance is uncoupling protein2 (UCP2), a transporter protein presents in mitochondrial inner membrane. Moreover, adiponectin is the most abundant adipocytokine, it may play a role in energy metabolism and gene expression of UCP2. The aim of this study was to investigate potential associations between the level of uncoupling protein 2 and adiponectin and their relationship with REE (Resting Energy Expenditure) in obese women with normal and low resting energy expenditure. A total of 49 subjects (women, 25-50 years old), were included in current study, 16 subjects with BMI > 30 and low resting energy expenditure, 17 subjects with BMI > 30 and normal resting energy expenditure and 16 non-obese subjects as a control group. Anthropometric, body composition parameters and resting energy expenditure were measured. Plasma adiponectin, UCP2 protein and total protein in PBMC were determined. Measured resting energy expenditure in obese subjects with low REE was significantly lower than other groups. Plasma adiponectin in the obese subjects with low REE was significantly lower compared to normal weight group. There was a significant relationship between 'UCP2 protein/Total protein' ratio and plasma adiponectin in obese group with low REE and in three groups when we pooled. There was a significant association between REE and plasma adiponectin in three groups when we pooled. There was a significant association between plasma adiponectin and REE. Moreover, there was a significant relationship between UCP2 and REE.

The synergistic effects of ω-3 fatty acids and nano-curcumin supplementation on tumor necrosis factor (TNF)-α gene expression and serum level in migraine patients.

Migraine is a destabilizing neuroinflammatory disorder characterized by recurrent headache attacks. Evidences show tumor necrosis factor (TNF)-α play a role in neuroimmunity pathogenesis of migraine. TNF-α increase prostanoid production, hyperexcitability of neurons, and nociceptor activation resulted in neuroinflammation and neurogenic pain. ω-3 fatty acids and curcumin exert neuroprotective and anti-inflammatory effects via several mechanisms including suppression of TNF-α gene expression and its serum levels. The aim of this study is an evaluation of synergistic effects of ω-3 fatty acids and nano-curcumin on TNF-α gene expression and serum levels in migraine patients. The present study performed as a clinical trial over a 2 month period included 74 episodic migraine patients in 4 groups and received ω-3 fatty acids, nano-curcumin, and combination of them or placebo. At the start and the end of the study, the gene expression of TNF-α and TNF-α serum levels was measured by real-time PCR and ELISA method, respectively. Our results showed that the combination of ω-3 fatty acids and nano-curcumin downregulated TNF-α messenger RNA (mRNA) significantly in a synergistic manner (P < 0.05). As relative to gene expression, a significant greater reduction in serum levels of TNF-α were observed in the combination group, but no significant differences in other groups. Supplementation with ω-3 fatty acids or nano-curcumin alone did not show significant reduction either in mRNA or serum levels of TNF-α. In addition, a much greater reduction in attack frequency was found in the combination group (P < 0.001). These findings indicated that ω-3 fatty acids and curcumin supplementation can be considered as a new promising approach in migraine management.

Vitamin A Decreases Cytotoxicity of Oxidized Low-Density Lipoprotein in Patients with Atherosclerosis.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is implicated in initiation and progression of atherosclerosis. Previously, we found that ox-LDL increases vulnerability of peripheral blood mononuclear cells (PBMCs) in atherosclerotic patients compared to controls. Vitamin A induces proliferation of PBMCs. The aim of this study was to determine the effect of vitamin A supplementation on PBMC survival against LDL and different doses of ox-LDL. METHOD: In this double-blind placebo-controlled trial, we recruited 35 atherosclerotic patients and 38 healthy controls and randomly allocated them into placebo and vitamin A groups, which received either placebo or 25,000 IU/day of vitamin A for 3 months. PBMCs were isolated, cultured, and stimulated by 1 µg/mL LDL as well as 1 µg/mL and 50 µg/mL ox-LDL. The stimulation indexes (SIs) of PBMCs were calculated to identify cell viability. Additionally, the circulating ox-LDL levels were measured by ELISA. RESULTS: Viability of PBMCs stimulated by 50 µg/mL ox-LDL significantly increased following vitamin A supplementation in patients (p < 0.01). The levels of circulating ox-LDL were not changed by vitamin A treatment. Ox-LDL levels were strongly and positively correlated to SI of PBMCs stimulated by 1 µg/mL LDL and1 µg/mL ox-LDL in all groups. CONCLUSION: Vitamin A decreases cytotoxicity of high-dose ox-LDL and improves PBMC viability. The protective effect of vitamin A is not mediated by an antioxidative mechanism, but may instead have been due to intracellular protection of the apoptotic machinery or induction of proliferation of the cells. Higher levels of ox-LDL increase PBMC irritability in all participants.

Maternal obesity and energy intake as risk factors of pregnancy-induced hypertension among Iranian women.

Pregnancy-induced hypertension is causing striking maternal, foetal and neonatal mortality and morbidity in the world. A case-control study was conducted on 113 women with gestational hypertension and 150 healthy pregnant women at Shahid Akbarabadi Hospital of obstetrics and gynaecology in south of Tehran. Women who were obese (OR 4.44; 95% CI 1.84-10.72) before pregnancy were more likely to develop gestational hypertension. Proportion of having excessive gestational weight gain was positively and significantly associated with development of gestational hypertension (OR 2.70; 95% CI 1.19-6.13). Furthermore, findings revealed that women who were in the highest quartile of mid-arm-circumference had a 3-fold increased risk of gestational hypertension compared to women in the lowest quartile (OR 8.93; 95% CI 2.16-36.93). We found that having been in the highest quartile of energy intake positively correlated with increased risk of gestational hypertension (OR 9.66; 95% CI 3.30-28.21). The results suggest pre-pregnancy obesity, excessive gestational weight gain, and increased intake of energy as potential risk factors of developing gestational hypertension.

Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes.

BACKGROUND: Both vitamin D deficiency and inflammation have been linked to cardiovascular disease, the major cause of death in diabetes. In this study, the effects of daily intake of vitamin D-fortified yoghourt drink (doogh) on systemic inflammatory biomarkers in subjects with type 2 diabetes (T2D) were investigated. SUBJECTS AND METHODS: In this 12-week randomized controlled trial, T2D subjects received either plain doogh (PD; containing 170 mg calcium and no detectable vitamin D/250 mL, n(1) = 50) or vitamin D3-fortified doogh (FD; containing 170 mg calcium and 500 IU/250 mL, n(2) = 50) twice a day. Glycemic status, body fat mass and systemic inflammatory biomarkers including serum highly sensitive C-reactive protein (hsCRP), serum amyloid A (SAA), interleukin(IL)-2, IL-6, IL-10 and tumour necrosis factor (TNF)-α were evaluated at the beginning and after the intervention. Data were expressed as either mean ± SD or median (interquartile range) whenever they had either normal or non-normal distribution, respectively. RESULTS: In the patients receiving the vitamin D fortified drink, compared with those receiving the unfortified drink, a significant increase in serum 25(OH)D was accompanied by significant changes in TNF-α (-57.9 (-264.6) versus +106.3 (683.2), p = 0.044), IL-6 (-6.3 (-69.2), p = 0.002), hsCRP (-0.39 (-1.50) versus +0.8 (1.52), p < 0.001), SAA (-14.2 ± 44.5 versus +5.6 ± 37.5 mg/L, p = 0.022) and IL-10 (+38.7 ± 157.0 versus -51.9 ± 165.2 ng/L, p = 0.013). The between-group differences of hsCRP, SAA and IL-6 changes remained significant even after controlling for changes quantitative insulin check index (p < 0.001, p < 0.001 and p = 0.009, respectively). CONCLUSIONS: Improvement of vitamin D status of T2D subjects resulted in amelioration of the systemic inflammatory markers. This may have preventive implications against cardiovascular disease and other diabetic complications.

A recombinant Plasmodium vivax apical membrane antigen-1 to detect human infection in Iran.

In Iran, Plasmodium vivax is responsible for more than 80% of the infected cases of malaria per year. Control interventions for vivax malaria in humans rely mainly on developed diagnostic methods. Recombinant P. vivax apical membrane antigen-1 (rPvAMA-1) has been reported to achieve designing rapid, sensitive, and specific molecular diagnosis. This study aimed to perform isolation and expression of a rPvAMA-1, derived from Iranian patients residing in an endemic area. Then, the diagnostic efficiency of the characterized Iranian PvAMA-1 was assessed using an indirect ELISA method. For this purpose, a partial region of AMA-1 gene was amplified, cloned, and expressed in pET32a plasmid. The recombinant His-tagged protein was purified and used to coat the ELISA plate. Antibody detection was assessed by indirect ELISA using rPvAMA-1. The validity of the ELISA method for detection of anti-P. vivax antibodies in the field was compared to light microscopy on 84 confirmed P. vivax patients and compared to 84 non-P. vivax infected individuals. The ELISA cut-off value was calculated as the mean+2SD of OD values of the people living in malaria endemic areas from a south part of Iran. We found a cut-off point of OD=0.311 that showed the best correlation between the sera confirmed with P. vivax infection and healthy control sera. A sensitivity of 81.0% and specificity of 84.5% were found at this cut off titer. A good degree of statistical agreement was found between ELISA using rPvAMA-1 and light microscopy (0.827) by Kappa analysis.

Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial.

BACKGROUND: Endothelial dysfunction has been proposed as the underlying cause of diabetic angiopathy that eventually leads to cardiovascular disease, the major cause of death in diabetes. We recently demonstrated the ameliorating effect of regular vitamin D intake on the glycemic status of patients with type 2 diabetes (T2D). In this study, the effects of improvement of vitamin D status on glycemic status, lipid profile and endothelial biomarkers in T2D subjects were investigated. METHODS: Subjects with T2D were randomly allocated to one of the two groups to receive either plain yogurt drink (PYD; containing 170 mg calcium and no vitamin D/250 mL, n1 = 50) or vitamin D3-fortified yogurt drink (FYD; containing 170 mg calcium and 500 IU/250 mL, n2 = 50) twice a day for 12 weeks. Anthropometric measures, glycemic status, lipid profile, body fat mass (FM) and endothelial biomarkers including serum endothelin-1, E-selectin and matrix metalloproteinase (MMP)-9 were evaluated at the beginning and after the 12-week intervention period. RESULTS: The intervention resulted in a significant improvement in fasting glucose, the Quantitative Insulin Check Index (QUICKI), glycated hemoglobin (HbA1c), triacylglycerols, high-density lipoprotein cholesterol (HDL-C), endothelin-1, E-selectin and MMP-9 in FYD compared to PYD (P < 0.05, for all). Interestingly, difference in changes of endothelin-1, E-selectin and MMP-9 concentrations in FYD compared to PYD (-0.35 ± 0.63 versus -0.03 ± 0.55, P = 0.028; -3.8 ± 7.3 versus 0.95 ± 8.3, P = 0.003 and -2.3 ± 3.7 versus 0.44 ± 7.1 ng/mL, respectively, P < 0.05 for all), even after controlling for changes of QUICKI, FM and waist circumference, remained significant for endothelin-1 and MMP-9 (P = 0.009 and P = 0.005, respectively) but disappeared for E-selectin (P = 0.092). On the contrary, after controlling for serum 25(OH)D, the differences disappeared for endothelin-1(P = 0.066) and MMP-9 (P = 0.277) but still remained significant for E-selectin (P = 0.011). CONCLUSIONS: Ameliorated vitamin D status was accompanied by improved glycemic status, lipid profile and endothelial biomarkers in T2D subjects. Our findings suggest both direct and indirect ameliorating effects of vitamin D on the endothelial biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01236846.

Vitamin-D-free regimen intensifies the spatial learning deficit in Alzheimer's disease.

Evidences support a link between nutrition and risk of neurodegenerative Alzheimer's disease (AD). This work was designed to find out if food regimens lacking vitamin D or with a supplement of vitamin D could affect spatial performances in the Alzheimeric animals. The experiment was done on the control and Alzheimeric (ALZ) animals on a normal regimen of food, as well as the Alzheimeric rats fed with regimens lacking vitamin D (ALZ-D) or supplemented with 1,25(OH)2D3 (ALZ+D). For learning the spatial task the animals were trained to locate a hidden platform in the Morris water maze. We found that the ALZ rats had an obvious lower performance compared with the control ones. Generally, the ALZ-D rats displayed a poorer spatial learning compared with either the ALZ or the ALZ+D rats. Vitamin D supplement did not significantly influence the spatial performance. We conclude that although vitamin D deficiency strengthens the spatial learning deficit in AD, a supplement of 1,25(OH)2D3 does not effectively underlie the maze performance. It can be concluded that subjects with AD must be protected from vitamin D inadequacy.

Nutritional Education and Its Effects on Household Food Insecurity in Southeastern Iran.

BACKGROUND: Food insecurity can affect health directly or indirectly through its impact on nutritional status. We aimed at determining the effects of nutrition education intervention on household food insecurity in Zahedan, southeast Iran. METHODS: The study was conducted using multi-stage sampling method. The first stage was a cross-sectional investigation whereby 2,160 households were studied in Zahedan in 2015. The prevalence of food insecurity was determined and food-insecure households were identified. Household food security status was assessed through the 18-item US Household Food Security Survey Module. In the second stage, based on the determined sample size of 150 households in each group, eligible households were randomly divided into the intervention and control groups. Before the educational intervention, questionnaires including demographic and socioeconomic information were completed for both groups. Then, data analysis was performed and the intervention was conducted on the intervention group. Six months post-intervention, a final assessment was made by interviewing the two groups to complete demographic, socioeconomic, and household food security questionnaires. RESULTS: The prevalence of food insecurity in the 2,160 households was 58.8%. After the intervention, the number of food-insecure households diminished by 22% in the intervention group, and these households were assigned to the food secure category. After controlling the confounding variables, the educational intervention was significantly effective in reducing food insecurity score (P<0.001). CONCLUSION: The findings demonstrated the beneficial role of nutritional education and the skills of resource management in modifying nutritional behaviors and improving food security in the study population.

A survey of Crimean-Congo haemorrhagic fever in livestock and ticks in Ardabil Province, Iran during 2004-2005.

Crimean-Congo haemorrhagic fever (CCHF) is a viral haemorrhagic fever caused by the CCHF virus. It is mainly transmitted to humans and animals by ticks. In recent y, large numbers of livestock have been transported across the border areas of Ardabil Province resulting in an outbreak of CCHF in the adjacent districts. A comprehensive study was carried out to assess the epidemiological aspects of the disease in this province. In the study area, 130 ticks were collected from randomly selected villages and classified into 9 species of hard tick and 2 species of soft tick. All ticks were analyzed for the presence of CCHF virus genome using gel-based and real-time reverse transcriptase polymerase chain reactions (RT-PCR). The results showed CCHF infection in almost 28% of ticks collectively. Also, of 56 livestock sera, around 39% were IgG-positive. The presence of anti-CCHF virus IgG antibodies and the CCHF virus genome in ticks points to a great hidden threat of an outbreak in these districts. Those in high-risk professions in this province should be informed and trained on the risk of CCHF with urgency.

Relationship between serum ferritin and inflammatory biomarkers with insulin resistance in a Persian population with type 2 diabetes and healthy people.

BACKGROUND: The correlation between body iron stores and inflammation with insulin resistance in type 2 diabetes is not thoroughly investigated, especially in the Persian population. METHODS: A cross-sectional study was designed in Tehran, Iran. Fifty-four people with type 2 diabetes and 53 matched healthy participants were included. Serum ferritin, total iron binding capacity, insulin resistance, C-reactive protein and tumor necrosis factor-alpha were measured in both groups. RESULTS: Diabetic patients had higher insulin resistance, hemoglobin A(1)C and serum ferritin. Significant positive correlations were observed between insulin resistance with serum ferritin and tumor necrosis factor-alpha and between serum ferritin and tumor necrosis factor-alpha in diabetic patients. CONCLUSIONS: Inter-relationship between insulin resistance, serum ferritin and TNF-alpha was found in type 2 diabetic patients. Serum iron even in the normal range had positive correlation with insulin resistance. It may be because the normal ranges determined for serum ferritin are too wide and the criteria for iron overload are too high.

Study of in vitro and in vivo effect of docosahexaenoic acid on rat C6 glioma.

Docosahexaenoic acid (DHA) may have potential anticarcinogenic effect. In the present study, effect of DHA on rat C6 glioma was tested. In vitro, cytotoxic effect of 50-400 microM DHA on C6 cells was evaluated and compared with linoleic acid (LA). In vivo, adult female Wistar rats implanted with C6 tumor, fed 1 ml of DHA oil (containing 73% DHA, 36 rats) or LA oil (containing 72-77% LA, 41 rats) daily, starting one week prior to tumor implantation until death or if survived, until 30 days after implantation. Another group of tumor bearing rats was treated with chloroethyl-cyclohexyl-nitrosourea (CCNU, 30 mg/kg, 31 rats) at day 8 post implantation to show if the result of oil supplementation is comparable to single agent chemotherapy. mRNA expression of p21 and p27 was determined in vitro at 100 and 150 microM of fatty acids and in tumors of rats supplemented with LA or DHA oils. In vitro, DHA, but not LA, had cytotoxic effect on C6 cells at 200 and 400 microM and DHA increased mRNA expression of p21 at 150 microM (p < 0.05). In rat glioma model, although a non-significant trend towards better survival was observed in DHA oil relative to LA oil group, the difference was not significant (p = 0.20). p21 and p27 mRNA expression in tumors of DHA oil group did not differ with LA oil group. Single dose of CCNU increased survival when compared to LA oil group (p < 0.001). In conclusion, intake of DHA at the dose or duration employed in the present study might be insufficient to bring about its cytotoxic action on rat's C6 brain tumor.

Nonlinear association between serum testosterone levels and coronary artery disease in Iranian men.

Previous studies have shown controversial results about the role of androgens in coronary artery disease (CAD). We performed this study to examine and compare the relationship between androgenic hormones and CAD using conventional linear statistical techniques as well as novel non-linear approaches. The study was conducted on 502 consecutive men who were referred for selective coronary angiography at Tehran Heart Center due to different indications. We studied the relationship between androgenic hormones and CAD by using the generalized linear models, generalized additive models, and neural networks. Free testosterone (fT), total testosterone (tT) and dehydroepiandrosterone sulfate levels in patients with significant CAD versus normal individuals were 6.69 +/- 3.20 pg/ml, 16.60 +/- 6.66 nm/l, and 113.38 +/- 72.9 microg/dl versus 7.12 +/- 3.58 pg/ml, 15.82 +/- 7.26 nm/l, and 109.03 +/- 68.19 microg/dl, respectively (P > 0.05). The Generalized linear models was unable to show any significant relationship between androgenic hormones and CAD, while generalized additive model and neural networks supported the significant effect of androgenic hormones on CAD. This finding suggests a nonlinear association of tT levels with CAD: lower levels have a preventive effect on CAD, whereas higher values increase the risk of CAD. Emphasizing the non-linearity of the variables may provide new insight into the possible explanation of the effect of androgenic hormones on CAD.

Resolvin D1 impacts on insulin resistance in women with polycystic ovary syndrome and healthy women.

AIMS: The aim of this study was to determine the association between the intake of omega-3 PUFAs and the serum level of resolvin D1 and insulin resistance in women with Polycystic Ovary Syndrome (PCOS) compared to healthy women. METHODS: A cross-sectional study was conducted in 2015-2016 in Tehran, Iran, among females referred to the infertility clinic at Valie-Asr Reproductive Health Research Centre. Thirty-one patients with PCOS (according to the criteria of the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM)) and 29 healthy, normal cycling (NC) women of similar age, weight and height were enrolled. Anthropometric measurements, levels of resolvin D1, fasting insulin, glucose levels and insulin resistance index (HOMA) for each of the patients were determined. RESULTS: Intakes of macronutrients (protein, carbohydrates, and total fat) and omega-3 PUFAs were higher in the PCOS group compared to the control group; also, the PCOS group had significantly higher resolvin D1, fasting insulin, glucose levels and HOMA when compared with the control group. Moreover, resolvin D1 correlated negatively with HOMA and fasting insulin levels among both the PCOS and control women. CONCLUSION: PCOS is associated with insulin resistance. We showed that omega-3 PUFAs can increase the synthesis of resolvin D1. Resolvin D1 is involved in insulin sensitivity by affecting insulin signaling and inflammatory pathways. Therefore, it can be a contributing factor in reducing insulin resistance in PCOS patients.

Effects of vitamin D supplementation on advanced glycation end products signaling pathway in T2DM patients: a randomized, placebo-controlled, double blind clinical trial.

BACKGROUND: Several researches have recommended vitamin D possible health benefits on diabetic complications development, but a few number of studies have been accomplished on the molecular and cellular mechanisms. Certain cellular pathways modification and also some transcription factors activation may protect cells from hyperglycemia condition induced damages. This study purpose was to determine the vitamin D supplementation effect on some key factors [advanced glycation end products (AGEs) signaling pathway] that were involved in the diabetic complications occurrence and progression for type-2 diabetes participants. METHODOLOGY: 48 type-2 diabetic patients (T2DM) randomly divided into two groups (n = 24 per group), receiving: 100-µg vitamin D or placebo for 3 months. At this study beginning and the end, the receptor expression for advanced glycation end products (RAGE) and glyoxalase I (GLO1) enzyme from peripheral blood mononuclear cells (PBMCs) and AGEs and tumor necrosis factor-α (TNF-α) serum levels were measured by the use of real-time PCR and ELISA methods, respectively. RESULTS: This study results demonstrated that vitamin D supplementation could down-regulate RAGE mRNA [fold change = 0.72 in vitamin D vs. 0.95 in placebo) P = 0.001)]. In addition, no significant changes were observed for GLO1 enzyme expression (P = 0.06). This study results also indicated that vitamin D serum level significantly increased in vitamin D group (P < 0.001). Moreover, AGES and TNF-α serum levels significantly reduced in vitamin D group, but they were remained unchanged in the placebo group. CONCLUSION: In conclusion, vascular complications are more frequent in diabetic patients, and vitamin D treatment may prevent or delay the complications onset in these patients by AGEs serum level and RAGE gene expression reducing.Trial registration NCT03008057. Registered December 2016.