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Fatemeh Ebrahimi,1,2 Amirhossein Sahebkar,3–5 Naheed Aryaeian,2 Naseh Pahlavani,6 Soudabeh Fallah,7 Nariman Moradi,8 Davoud Abbasi,9 Agha Fatemeh Hosseini10 1Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran; 3Halal Research Center of IRI, FDA, Tehran, Iran; 4Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; 5Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 6Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran; 7Department of Clinical Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; 8Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran; 9Department of Internal Medicine, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; 10Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, IranCorrespondence: Naheed AryaeianDepartment of Nutrition, School of Public Health, Iran University of Medical Sciences, Shahid Hemmat Expressway, Iran University of Medical Sciences, Hemat Highway next to Milad Towe Tehran, Tehran 1449614535, IranTel +98-912-3093353Fax +98-21-8862253Email Aryaeian.n@iums.ac.irBackground: Type 2 diabetes (T2D) is accompanied by elevated inflammation, oxidative stress, hyperlipidemia and hyperglycemia which all contribute to cardiovascular disease pathogenesis. Saffron as a complementary medicine and source of antioxidants could play a role in alleviating diabetes and its complications. The aim of this study was to determine the effects of saffron supplementation as an adjunct therapy in T2D.Patients and methods: This randomized controlled trial included 80 T2D patients with a mean age of 54.1 years. Participants were randomly assigned into two groups to take either saffron tablets (100 mg/day; n=40) or placebo (n=40) for 12 weeks. Fasting blood samples were obtained at the beginning and after the intervention period to quantify glycemic factors, lipid profile, and biomarkers of inflammation and oxidative stress. Anthropometric indices and dietary intakes were also measured at baseline and at study end.Results: Compared with placebo, saffron supplementation resulted in significant decreases in waist circumference (p0.05).Conclusion: Overall, 12 weeks of saffron supplementation in diabetic patients had beneficial effects on waist circumference and serum MDA levels. However, saffron did not influence other evaluated cardio metabolic risk markers in diabetic patients.Keywords: crocus sativus, diabetes mellitus, type 2, dysglycemia, lipid profile, inflammation mediators

BACKGROUND: Despite beneficial effects of conjugated linoleic acids (CLAs) in animal studies, there is little information on their effects on human inflammatory and autoimmune diseases. AIM: To investigate the effects [...]

Background: Rheumatoid arthritis (RA) is an autoimmune disorder that results in joint dysfunction, inflammation, and increased mortality., Hypothesis/purpose: The aim of this study was to evaluate the efficacy of purslane supplements on clinical outcomes, as well as inflammation and antioxidant markers in patients with RA., Study Design: A double-blinded randomized controlled clinical trial., Methods: In this 12-week trial, 86 participants aged between 20 and 79 were divided into two groups. The intervention group (n = 43) received a 500 mg purslane capsule twice a day, while the control group (n = 43) received a placebo capsule of the same shape and dosage., Results: Seventy-seven patients (37 from the control group and 40 from the purslane group) completed the study. Purslane capsule intake significantly declined visual analog scale (53.38 ± 23.81 vs. 26.25 ± 17.27, p ≤ 0.001), swollen joint count (4.42 ± 3.36 vs. 1.60 ± 1.64, p ≤ 0.001), tender joint count (8.20 ± 5.93 vs. 2.78± 2.15, p ≤ 0.001), High-sensitivity C-reactive protein (p ≤ 0.001), disease activity score (DAS28) (5.17 ± 1.30 vs. 3.48 ± 1.20, p ≤ 0.001) and increased Superoxide dismutase (p = .037), and total antioxidant capacity (p ≤ 0.001) changes. Furthermore, Morning stiffness (p=.002) and Physician Global Assessment (p = .026) significantly decreased in the purslane group compared to the placebo group at the end of the trial. There was a significant decrease in tumor necrosis factor-α (2.885 ± 2.068 vs. 2.330 ± 1.121, p = .046), and erythrocyte sedimentation rate (36.52 ± 20.04 vs. 26.70 ± 22.59, p = .007) levels in the purslane group., Conclusion: Therefore, supplementation with purslane could lead to improved clinical outcomes, and inflammatory and antioxidant indicators in RA patients., Competing Interests: Declaration of competing interest The authors declared that there is no conflict of interest., (Copyright © 2024. Published by Elsevier GmbH.)

This study was designed to assess the relationship between dietary insulin index (DII) and dietary insulin load (DIL) and rheumatoid arthritis (RA) risk in a case-control study. This study enrolled ninety-five newly diagnosed RA patients and 200 age- and sex-matched healthy controls. Dietary intakes were assessed using a validated 168-item semi-quantitative FFQ. DII and DIL were calculated using food insulin index values from previously published data. In the unadjusted model, individuals in the highest DIL tertile had the significantly higher odds of RA than those in the lowest tertile of the DIL scores (OR = 1·32, 95 % CI (1·15, 1·78), P for trend = 0·009). After adjusting for confounders, the risk of RA was 2·73 times higher for participants in the highest tertile of DIL than for those in the lowest tertile (OR = 2·73, 95 % CI (1·22, 3·95), P for trend < 0·001). In addition, patients in the highest DII tertile had higher risk of RA than those in the first tertile (OR = 2·22, 95 % CI (1·48, 3·95), P for trend = 0·008). This association persisted after adjusting for potential confounders (OR = 3·75, 95 % CI (3·18, 6·78), P for trend = 0·002). Our findings suggest that diets high in DII and DIL may increase the risk of developing RA, independent of other potential confounders. These findings can be verified by more research, particularly with a prospective design.

This case-control study investigated the link between dietary branched-chain amino acids (BCAAs) and the risk and severity of rheumatoid arthritis (RA). We assessed dietary BCAA intake in 95 RA patients and 190 matched controls using a food frequency questionnaire. We also assessed the disease severity using the disease activity score 28 (DAS-28), ESR, VAS, morning stiffness, and tender and swollen joints. Higher BCAA intake, expressed as a percentage of total protein, was significantly associated with increased risk of RA for total BCAAs (OR 2.14, 95% CI 1.53-3.00, P < 0.001), leucine (OR 2.40, 95% CI 1.70-3.38, P < 0.001), isoleucine (OR 2.04, 95% CI 1.46-2.85, P < 0.001), and valine (OR 1.87, 95% CI 1.35-2.59, P < 0.001). These associations remained significant even after adjusting for potential confounders (P < 0.001). However, BCAA intake did not show any significant association with RA severity in either crude or multivariate models (P > 0.05). Our findings suggest that higher dietary BCAA intake may contribute to the development of RA, but further research is needed to confirm these observations and explore the underlying mechanisms., (© 2024. The Author(s).)

Consumption of plum does not yet clearly affect the lipid profile. To ascertain the advantages of plum consumption on adult lipid profiles, we conducted a systematic review and meta-analysis. We used pertinent keywords to search the databases of PubMed, Scopus, and ISI Web of Science up to November 10th, 2022, in order to find trials that were eligible. According to the analyses, eating plum significantly lowers LDL levels compared to controls (WMD: -12.50 mg/dL, 95% CI: -22.06, -2.94, p  = .010). Although plum consumption did not result in significant changes in TG (WMD: 0.56 mg/dL, 95% CI: -6.02, 7.15, p  = .866), TC (WMD: -12.35 mg/dL, 95% CI: -25.05, 0.37, p  = .057), and HDL concentrations (WMD: -0.39 mg/dL, 95% CI: -4.69, 3.89, p  = .855) compared to the control group. Intake of plums, particularly the intervention type of dried plums, significantly decreased TC levels in unhealthy subjects, according to subgroup analysis. The consumption of plums had a notably statistically significant effect on LDL levels when the intervention type was dried plum and unhealthy subjects were enrolled. Due to the very low to moderate quality of meta-evidence, to show how eating plum improves lipid profile, further high-quality research are still essential., Competing Interests: The authors declared that there is no conflicts of interest., (© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: Depression is one of the most common psychological disorders among multiple sclerosis (MS) patients that characterized as the first symptoms. Ellagic acid is a natural polyphenol that may have neuroprotective properties through antioxidant, anti-inflammatory, and immunomodulatory effects., Purpose: The aim of the present study was to investigate the effects of Ellagic acid on circulating levels of brain derived neurotrophic factor (BDNF), interferon-γ (IFN-ƴ), nitric oxide (NO), nuclear factor erythroid-2-related factor 2 (Nrf2), cortisol, serotonergic system, and indoleamine 2, 3-dioxygenase (IDO) gene expression in MS patients with mild to moderate depressive symptoms., Study Design: A randomized triple-blind clinical trial., Methods: The eligible patients according to the inclusion criteria were randomly divided into two groups: either 180 mg Ellagic acid (Axenic company) (n = 25) or 180 mg maltodextrin (n = 25) group for 12 weeks. The Ellagic acid supplement were identical to placebo in shape, color and odor. Serum BDNF, NO, Nrf2, cortisol, serotonin, and IFN-ƴ were measured by ELISA kit in the baseline and end of the study. Also, demographic characteristics, anthropometric measurements, physical activity, food intake, Beck Depression Inventory-II (BDI-II) and expanding disability status scale (EDSS) questionnaires, as well as IDO gene expression were assessed. SPSS software version 24 was used for statistical analysis., Results: Fifty patients were evaluated, and a significant decrease in BDI-II (p = 0.001), IFN-ƴ (p = 0.001), NO (p = 0.004), cortisol (p = 0.015), IDO gene expression (p = 0.001) and as well as increased the level of BDNF (p = 0.006) and serotonin (p = 0.019) was observed among those who received 90 mg Ellagic acid twice a day for 12 weeks versus control group. However, there were no significant differences between groups for Nrf2 levels (p>0.05) at the end of study., Conclusion: The current study indicates that Ellagic acid intervention has a favorable effect on depression in MS patients. This is achieved by reducing BDI-II scores, as well as levels of NO, cortisol, IFN-ƴ, and IDO gene expression. Furthermore, we found a significant elevation in circulating levels of BDNF and serotonin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Cardamom has the potential to offer anti-inflammatory and antihypertensive advantages, but the findings from clinical trials have been inconsistent. To address this knowledge gap, the present systematic review and meta-analysis were conducted to evaluate the anti-inflammatory and antihypertensive effects of cardamom in adults. We systematically searched databases including PubMed, Scopus, and ISI Web of Sciences, for papers published up to October 2022 to identify clinical studies. Eight eligible studies were included in the meta-analysis. A fixed model was used to estimate weighted mean difference (WMD), standardized mean difference (SMD), and 95% confidence interval (95% CI). The results showed that cardamom significantly reduced the levels of inflammatory factors, including hs-CRP (SMD: -0.60 mg/dL; 95% CI: -0.78 to 0.42), IL-6 (WMD: -1.25 mg/dL; 95% CI: -1.48 to -1.03), TNF-α (WMD: -2.10 kg; 95% CI: -2.36 to -1.84, p  < .001), and measures of systolic (WMD: -0.54 mmHg, 95% CI: -0.88, -0.19, p  = .002) and diastolic (WMD: -0.90 mmHg; 95% CI: -1.07 to -0.73) blood pressure. The current meta-analysis showed that cardamom can help reduce inflammation and improve blood pressure. However, due to the limited number of studies, caution must be exercised when interpreting the current results., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Bone marrow mesenchymal stem cells (BM-MSCs) have a momentous function in the composition of the bone marrow microenvironment because of their many valuable properties and abilities, such as immunomodulation and hematopoiesis. The features and actions of MSCs are influenced by senescence, which may be affected by various factors such as nutritional/micronutrients status, e.g., vitamin D. This study aimed to examine the effects of a high-calorie diet (HCD) with/without vitamin D on BM-MSCs senescence. In the first phase, 48 middle-aged rats were fed a normal chow diet (NCD, n = 24) and an HCD (n = 24) for 26 weeks. Afterward, the rats in each group were randomly divided into three equal subgroups. Immediately, eight-rat from each diet group were sacrificed to assess the HCD effects on the first phase measurements. In the second phase, the remaining 4 groups of rats were fed either NCD or HCD with (6 IU/g) or without vitamin D (standard intake: 1 IU/g); in other words, in this phase, the animals were fed (a) NCD, (b) NCD plus vitamin D, (c) HCD, and (d) HCD plus vitamin D for 4 months. BM-MSCs were isolated and evaluated for P16 INK4a , P38 MAPK, and Bmi-1 gene expression, reactive oxygen species (ROS) levels, SA-β-gal activity, and cell cycle profile at the end of both phases. After 26 weeks (first phase), the ROS level, SA-β-gal-positive cells, and cells in the G1 phase were significantly higher in HCD-fed rats than in NCD-fed ones (P < 0.05). HCD prescription did not significantly affect cells in the S and G2 phases (p > 0.05). Compared with the NCD-fed animals, P16 INK4a and P38 MAPK gene expression were up-regulated in the HCD-fed animals; also, Bmi-1 gene expression was down-regulated (P < 0.05). BM-MSCs from vitamin D-treated rats (second phase) exhibited reduced mRNA levels of P16 INK4a and P38 MAPK genes and increased Bmi-1 mRNA levels (all P < 0.05). Vitamin D prescription also declined the percentage of SA-β-gal-positive cells, ROS levels, and the cells in the G1 phase and increased the cells in the S phase in both NCD and HCD-fed animals (P < 0.05). The reduction of the cells in the G2 phase in rats fed with an NCD plus vitamin D was statistically non-significant (P = 0.128) and significant in HCD plus vitamin D rats (P = 0.002). HCD accelerates BM-MSCs senescence, and vitamin D reduces BM-MSCs senescence biomarkers., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Previous studies have shown that hesperidin may have beneficial effects on depression; however, to the best of our knowledge, no clinical trial has yet been conducted in this area. The aim of the present study was, therefore, to determine the effects of hesperidin on depression, serum brain-derived neurotrophic factor (BDNF), and serum cortisol levels in post-coronary artery bypass graft (CABG) patients. Toward this goal, 73 post-CABG patients with depression symptoms were enrolled. The participants were randomly divided into two groups to receive either 200 mg/day hesperidin ( n  = 38) or placebo ( n  = 35) for 12 weeks. Depressive symptoms, serum BDNF, and cortisol levels were then assessed at the baseline and after intervention. Beck Depression Inventory-II (BDI-II) was also used to determine the severity of depression. Sixty-six patients completed the trial. Hesperidin decreased depression severity after 12 weeks, as compared to placebo ( p  = .004), but serum BDNF and cortisol were not statistically significantly different in the two groups after the intervention. Subgroup analyses also showed that, while in the patients with mild depression, the score of BDI-II was significantly different in the hesperidin and placebo groups after intervention; there was no difference in the severity of depression between the two groups in patients with moderate-to-severe depression. To conclude, a dose of 200 mg/day hesperidin may reduce depressive symptoms after 12 weeks in post-CABG patients with mild depression., Competing Interests: All authors declared no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: Multiple sclerosis (MS) is a chronic autoimmune disease. Ellagic acid is a natural polyphenol and affects the fate of neurons through its anti-inflammatory and antioxidant properties. The present study aimed to investigate ellagic acid effects on disease severity, the expression of involved genes in the pathogenesis of MS, and the levels of related cytokines., Methods: The present study was a triple-blind clinical trial. Eligible patients were randomly assigned to two groups: Ellagic acid (25 subjects) for 12 weeks, receiving 180 mg of Ellagic acid (Axenic, Australia) and the control group (25 subjects) receiving a placebo, before the main meals. Before and after the study, the data including general information, foods intake, physical activity, anthropometric data, expanded disability status scale (EDSS), general health questionnaire (GHQ) and pain rating index (PRI), fatigue severity scale (FSS) were assessed, as well as serum levels of interferon-gamma (IFNγ), interleukin-17 (IL-17), interleukin-4 (IL-4) and transforming growth factor-beta (TGF-β), nitric-oxide (NO) using enzyme-linked immunoassay (ELISA) method and expression of T-box transcription factor (Tbet), GATA Binding Protein 3 (GATA3), retinoic acid-related orphan receptor-γt (RORγt) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were determined using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) method., Findings: Ellagic acid supplementation led to a reduction in IFNγ, IL-17, NO and increased IL-4 in the ellagic acid group, however in the placebo group no such changes were observed (-24.52 ± 3.79 vs. -0.05 ± 0.02, p < 0.01; -5.37 ± 0.92 vs. 2.03 ± 1.03, p < 0.01; -18.03 ± 1.02 vs. -0.06 ± 0.05, p < 0.01, 14.69 ± 0.47 vs. -0.09 ± 0.14, p < 0.01, respectively). Ellagic acid supplementation had no effect on TGF-β in any of the study groups ( p > 0.05). Also, the Tbet and RORγt genes expression decreased, and the GATA3 gene expression in the group receiving ellagic acid compared to control group significantly increased (0.52 ± 0.29 vs. 1.51 ± 0.18, p < 0.01, 0.49 ± 0.18 vs. 1.38 ± 0.14, p < 0.01, 1.71 ± 0.39 vs. 0.27 ± 0.10, p < 0.01). Also, ellagic acid supplementation led to significant decrease in EDSS, FSS and GHQ scores ( p < 0.05), and no significant changes observed in PRI score ( p > 0.05)., Conclusion: Ellagic acid supplementation can improve the health status of MS patients by reduction of the inflammatory cytokines and Tbet and RORγt gene expression, and increment of anti-inflammatory cytokines and GATA3 gene expression. Clinical trial registration : (https://en.irct.ir/trial/53020), IRCT20120415009472N22., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jafari Karegar, Aryaeian, Hajiluian, Suzuki, Shidfar, Salehi, Ashtiani, Farhangnia and Delbandi.)

Hesperidin, as an antioxidant and anti-inflammatory agent, has beneficial effects on cardiovascular diseases. This study aimed to determine the effects of hesperidin supplementation on inflammation, oxidative stress, and lipid profile in depressed coronary artery bypass graft surgery (CABG) patients. Eighty patients after coronary artery bypass graft surgery participated in this clinical trial and were randomly divided into two groups. The intervention group received 200 mg/d pure hesperidin supplement and the second group received placebo for 12 weeks. Both groups continued their usual diet. Serum concentrations of inflammatory and stress oxidative markers (hs-CRP, P-selectin, and ox-LDL) were measured and compared at baseline and the end of the intervention. The changes in serum levels of triglyceride were significantly different between the two groups ( p  < .05). HDL-c significantly increased in groups but the differences between the two groups were not statistically significant ( p  > .05). Hesperidin did not affect FBS, other lipid parameters, hs-CRP, P-selectin, and OX-LDL ( p  > .05). SBP and DBP differences were not statistically significant ( p  > .05). After 12 weeks of intervention, hesperidin reduced serum levels of triglyceride in depressed post-CABG patients., Competing Interests: The authors have declared that there is no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Coenzyme Q10 is a potent antioxidant and is necessary for energy production in mitochondria. Clinical data have suggested that coenzyme Q10 (CoQ10) has some beneficial effects on liver function. However, these results are equivocal. This systematic review and meta-analysis aimed to clarify the effect of coenzyme Q10 supplementation on the serum concentration of liver function enzymes. We searched the online databases using relevant keywords up to April 2022. Randomized clinical trials (RCTs) investigating the effect of CoQ10, compared with a control group, on serum concentrations of liver enzymes were included. We found a significant reduction following supplementation with CoQ10 on serum concentrations of alanine aminotransferase (ALT) based on 15 effect sizes from 13 RCTs (weighted mean difference [WMD] = -5.33 IU/L; 95% CI: -10.63, -0.03; p  = .04), aspartate aminotransferase (AST) based on 15 effect sizes from 13 RCTs (WMD = -4.91 IU/L; 95% CI: -9.35, -0.47; p  = .03) and gamma-glutamyl transferase (GGT) based on eight effect sizes from six RCTs (WMD = -8.07 IU/L; 95% CI: -12.82, -3.32; p  = .001; I 2  = 91.6%). However, we found no significant effects of CoQ10 supplementation on alkaline phosphatase concentration (WMD = 1.10 IU/L; 95% CI: -5.98, 8.18; p  = .76). CoQ10 supplementation significantly improves circulating ALT, AST, and GGT levels; therefore, it might positively affect liver function. Further high-quality RCTs with more extended intervention periods and larger sample sizes are recommended to confirm our results., Competing Interests: Authors declared no personal or financial conflicts of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders associated with a high risk of diabetes, atherosclerosis, and cardiovascular disease. The purpose of this study was to determine the effect of sumac powder on clinical symptoms and laboratory parameters in women with PCOS. The double-blind randomized controlled clinical trial was conducted on 88 women with PCOS randomly assigned to the intervention and control groups. The intervention group received three capsules each containing 1 g of sumac powder for 12 weeks. All data and serum levels of sex hormone, hs-CRP, glucose, and lipid profiles were measured at the baseline and at the end of the study. Data were analyzed using SPSS version 25 software. The ANCOVA test results showed that hs-CRP level was significantly reduced in the intervention group (p = .008). Blood glucose and lipid profiles in the intervention group were significantly reduced compared to the placebo group (p < .05). Insulin sensitivity and HDL levels were increased significantly in the Sumac group after the intervention (p < .05). Sumac powder can reduce the inflammatory effects, and glycemic status and lipid profile of polycystic ovaries in affected women, but has no significant effect on anthropometric parameters and sex hormones., (© 2023 John Wiley & Sons Ltd.)

Background: Depression is more common in diabetic patients, with a 1.5-fold increased risk of death.Melissa officinalis (M. officinalis) have anti-diabetic and anti-depression activities. The study aimed to determine the efficacy of M. officinalis extract on depression, anxiety, and sleep quality in patients with type 2 diabetes with depressive symptoms., Methods: In this double-blind clinical trial, 60 volunteer patients (age range 20-65 years) with type 2 diabetes mellitus with symptoms of depression were randomized into the intervention (received 700 mg/day hydroalcoholic extract; n = 30) or control group (received 700 mg/day toasted flour; n = 30). Dietary intake, physical activity, anthropometric indices, FBS (Fasting blood sugar), hs-CRP(High-sensitivity C-reactiveprotein), depression, anxiety, and sleep quality were determined at the beginning and end of the study. Depression and anxiety were assessed by Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively; sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI)., Results: Sixty participants received M. officinalis extract or placebo, of which 44 patients completed the 12-week double-blind clinical trial. After 12-week the mean change of depression and anxiety scores were statistically significant between the two groups (p < 0.001 and p = 0.04, respectively), but no significant differences were observed in FBS, hs-CRP, anthropometric indices, sleep quality, and blood pressure.In the intervention group, there was a significant decrease in depression and anxiety severity(p < 0.001 and p = 0.01, respectively) at the end of the study compared to the baseline., Trial Registration: All protocols in this study were followed in accordance with the Helsinki Declaration (1989 revision). Ethical approval for this study was obtained from the Iran University of Medical Sciences Ethics committee (IR.IUMS.FMD.REC 1396.9413468004; research.iums.ac.ir). The study was registered at the Iranian Registry of Clinical Trials (IRCT201709239472N16); Registration date: 09/10/2017., (© 2023. The Author(s).)

Background: Hematological inflammatory indices are currently suggested to assess systemic inflammation. This study aims to investigate a vitamin D supplementation effect on hematological indices of inflammation in rats., Method: Forty-eight middle-aged male rats were allocated into a normal diet (ND) group (10% fat) and a high-fat diet (HFD) group (60% fat). The animals were fed for 26 weeks. After this period, each group was randomly divided into three subgroups, each of 8 rats: Group (1): animals were fed the ND and HFD containing 1 IU/g vitamin D for 4 months, group (2): animals were fed the ND and HFD containing 6 IU/g vitamin D for 4 months and group (3): animals were euthanized to evaluate the HFD effect. Serum 25-hydroxyvitamin D level, white blood cell count (WBCs), platelet count, platelet crit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) were measured., Results: The HFD, significantly increased body weight, PCT, PDW, PLR, NLR, and MLR and significantly reduced serum vitamin D levels compared to the ND (P < 0.05). There was a significant decrease in food intake, MPV, PDW, and NLR after vitamin D supplementation in the ND-fed group (P < 0.05). A significant reduction in platelet count, PCT, and MLR was observed after vitamin D supplementation in HFD-fed rats (P < 0.05)., Conclusions: In our study, some hemogram-derived inflammatory indices were higher in the HFD-fed group, and vitamin D supplementation lowering effects on some hematological indices were seen in both ND and HFD groups., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 International Journal of Preventive Medicine.)

Background: According to the worldwide increasing prevalence of non-alcoholic fatty liver disease (NAFLD), the present study aimed to investigate the mechanism effects of saffron consumption on preventing NAFLD in a rat model., Methods: In an experimental study, 12 rats were randomly divided into 2 groups to be evaluated in the prevention phase for 7 weeks. In the prevention phase, the animals were randomly assigned to either fed HFHS + 250 mg/kg saffron (S) or fed with HFHS. Afterward, parts of the liver were excised for histopathologic examination. Plasma concentrations of ALT, AST, GGT, ALP, serum lipids, insulin concentrations, plasma glucose, hs-CRP, and TAC were measured. Moreover, Also, the gene expression of 6 target genes was evaluated, including FAS, ACC1, CPT1 ، PPARα ، DGAT2, and SREBP 1-c at the beginning and end of the study. Also, the differences among groups were evaluated by the Mann-Whitney test for non-normal data and the independent t test for normal data., Results: The prevention phase groups have a significant elevation in body weight ( P = 0.034) and food intake ( P = 0.001) of the HFHS group versus HFHS + 250 mg/kg S group. Also, there was a significant difference between groups 1 and 2 for ALT (P = 0.011) and AST ( P = 0.010), and TG ( P = 0.040). The HFHS group had higher plasma levels of FBS ( P = 0.001), insulin ( P = 0.035), HOMA-IR ( P = 0.032), and lower TAC ( P = 0.041) versus the HFHS+ S group. Also, the difference between HFHS + 250 mg/kg S and HFHS for PPARα gene expression was significant ( P = 0.030)., Conclusion: The present study showed that consumption of saffron could prevent developing NAFLD in rats at least partially through modulation in gene expression of PPARα., Competing Interests: The authors declare that they have no competing interests., (© 2023 Iran University of Medical Sciences.)

Objectives: Cornus mas fruit has various antioxidants and anti-inflammatory properties, so this study aims at assessing its effect on menopausal symptoms and sex hormones in postmenopausal women., Methods: In the current randomized, double-blind clinical trial, 84 individuals (42 per group) were participated. C mas hydroalcoholic extract was prepared, and participants received 300 mg C mas extract or placebo three times a day (900 g in total) for 8 weeks. The demographic, dietary intake, and physical activity information were gathered. Anthropometric indices were measured by standard methods. Furthermore, menopause symptoms were assessed by Greene Climacteric Scale. Also, sex hormones were measured by enzyme-linked immunosorbent assay., Results: Based on the results, there was a significant difference in total Greene score reduction between the intervention and placebo groups (-3.19 ± 0.54, -0.76 ± 0.32, and P < 0.001). In addition, vasomotor symptoms had a remarkable decrease in the C mas extract group (P < 0.001). Also, the intervention group demonstrated a decreasing trend in the number and duration of hot flushes. Moreover, follicle-stimulating hormone remarkably decreased and estradiol increased in the intervention group (P = 0.016 and P = 0.018)., Conclusions: It has been found that the extract of C mas fruit has a favorable effect on vasomotor symptoms, sex hormones, and related complications in women experiencing menopausal symptoms., Competing Interests: Financial disclosures/conflicts of interest: None reported., (Copyright © 2022 by The North American Menopause Society.)

Background: There are randomized controlled trials (RCTs) about the zinc supplementation effect on circulating levels of brain-derived neurotrophic factor (BDNF). However, the findings of these studies are inconsistent. The purpose of this systematic review and meta-analysis was to determine the zinc supplementation effect on BDNF and zinc levels in published RCTs., Methods: We searched PubMed/Medline, Cochrane, Scopus, ISI Web of Science, EMBASE, "Clinicaltrials.gov", "Cochrane Register of Controlled Trials", "IRCT" and also key journals up to 2019. RCTs with two intervention (zinc) and control (placebo) groups that evaluated zinc supplementation efficacy on BDNF levels were included. Study heterogeneity was assessed, and then, meta-analysis was performed using the fixed-effects model., Results: Four studies were included in the present secondary analysis. Compared with placebo, zinc supplementation significantly enhanced circulating levels of BDNF [(SMD): 0.31, 95% confidence interval (CI): (0.22, 0.61)] and zinc [(SMD): 0.88, 95% CI: (0.54, 1.22)] with no considerable heterogeneity among the studies [( Q = 3.46; P = 0.32; I2% = 13.4); (Q = 2.01; P = 0, 37; I2% = 0.5), respectively]., Conclusions: Our results propose that zinc supplementation can increase the circulating levels of BDNF and zinc. This study was registered at PROSPERO as CRD42020149513., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 International Journal of Preventive Medicine.)

Background: Vascular dysfunction is a major complication of diabetes mellitus that leads to cardiovascular disease (CVD). This study aimed to examine the effects of omega-3 consumption on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus (T1DM)., Methods: In this randomized, double-blind, placebo-controlled clinical trial, 51 adolescents (10-18 years) with T1DM completed the study. Patients received 600 mg/day [containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA)] of omega-3 or placebo for 12 weeks. Flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, blood urea nitrogen (BUN), creatinine, fasting blood sugar (FBS), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), serum insulin (SI), urine albumin-creatinine ratio (uACR), blood pressure, and anthropometric indices were assessed at the baseline and after the intervention., Results: Following supplementation, omega-3 significantly increased FMD (3.1 ± 4.2 vs. -0.6 ± 4%, p = 0.006) and decreased TG (-7.4 ± 10.7 vs. -0.1 ± 13.1 mg/dl, p = 0.022) in comparison with the placebo group. However, no significant difference was observed regarding CIMT (-0.005 ± 0.036 vs. 0.003 ± 0.021 mm, p = 0.33). Although hs-CRP was significantly decreased within the omega-3 group ( p = 0.031); however, no significant change was observed compared to placebo group ( p = 0.221). Omega-3 supplementation had no significant effect on other variables., Conclusion: Given the elevation in FMD and reduction in TG, omega-3 supplementation can improve vascular function and may reduce the risk of cardiovascular disease in adolescents with T1DM patients., (Copyright © 2022 Khorshidi, Sayyari, Aryaeian, Olang, Alaei, Khalili, Hosseini and Salehi.)

Experimental and some clinical studies have shown beneficial effects of rosemary leaf on liver function and biochemical parameters. The present study aimed to examine the impact of rosemary leaf powder with a weight loss diet in patients with nonalcoholic fatty liver disease. In a randomized double-blinded clinical trial, 110 patients were randomly assigned to receive either 4 g rosemary leaf or placebo (starch) powders for 8 weeks. In addition, all participants in the study were given weight loss diet and physical activity recommendations. Compared with baseline, alanine aminotransferase (p < .001), aspartate aminotransferase (p < .001), alkaline phosphatase (p < .001), gamma glutamyltransferase (p < .001), fasting blood glucose (p < .001), fasting insulin (p < .001), insulin resistance (p < .001), total cholesterol (p = .003), triglyceride (p < .001), low-density lipoprotein cholesterol (p < .001), and anthropometric indices (weight, body mass index, and waist circumferences) decreased significantly in the rosemary and placebo group with weight loss. However, after 8 weeks, no significant difference between the rosemary and placebo groups was detected in the variables as mentioned above except homeostasis model assessment of β-cell dysfunction (p = .014). The findings of the current clinical trial study revealed that rosemary group did produce changes, but they were not statistically different from those produced by the diet/activity intervention alone., (© 2022 John Wiley & Sons Ltd.)

Background: Type 1 diabetes is a main health burden with several related comorbidities. It has been shown that endothelial function, vascular structure, and metabolic parameters are considerably disrupted in patients with type 1 diabetes. Omega-3 as an adjuvant therapy may exert profitable effects on type 1 diabetes and its complications by improving inflammation, oxidative stress, immune responses, and metabolic status. Because no randomized clinical trial has examined the effects of omega-3 consumption in children and adolescents with type 1 diabetes; the present study aims to close this gap., Methods: This investigation is a randomized clinical trial, in which sixty adolescents with type 1 diabetes will be randomly assigned to receive either omega-3 (600 mg/day) or placebo capsules for 12 weeks. Evaluation of anthropometric parameters, flow-mediated dilation (FMD) as an endothelial function marker, carotid intima-media thickness (CIMT) as a vascular structure marker, proteinuria, biochemical factors including glycemic and lipid profile, blood urea nitrogen (BUN), creatinine, high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR), as well as blood pressure will be done at the baseline and end of the trial. Also, dietary intake and physical activity will be assessed throughout the study. Statistical analysis will be performed using the SPSS software (Version 24), and P < 0.05 will be considered statistically meaningful., Discussion: It is hypothesized that omega-3 supplementation may be beneficial for the management of type 1 diabetes and its complications by reducing inflammation and oxidative stress and also modulating immune responses and glucose and lipid metabolism through various mechanisms. The present study aims to investigate any effect of omega-3 on patients with type 1 diabetes., Ethical Aspects: This trial received approval from Medical Ethics Committee of Iran University of Medical Sciences, Tehran, Iran (IR.IUMS.REC.1400.070)., Trial Registration: Iranian Registry of Clinical Trials IRCT20210419051010N1 . Registered on 29 April 2021., (© 2021. The Author(s).)

Background: Colorectal cancer is the third leading to death type of cancer in the world. The therapeutic guideline varied between different methods. As the main therapeutic guideline is chemotherapy, recent studies had shown utilization of natural products in combination with conventional medication, elevate the efficiency of chemotherapeutic methods. Kombucha is a traditional beverage obtained from the fermentation of green tea as a rich source of flavonoid medicinal plant. This study aimed to evaluate the natural potential of combination therapy of this natural product with doxorubicin as a chemotherapeutic agent., Materials and Methods: The study was performed as in vitro evaluation of biological activity of kombucha on HCT-116 cell line (human colon cancer cell line). The cytotoxic effect of different kombucha beverages (fermented green tea) in comparison with green tea extract was evaluated by dimethylthiazolyl tetrazolium bromide (MTT) assay. In the next step, anticancer activity of doxorubicin as a general guideline chemotherapeutic agent in combination with kombucha was evaluated by cell cycle analysis and apoptosis assay flow cytometry. Apoptotic genes expression pattern was determined using real-time polymerase chain reaction. The experiments were designed in three independent replications and statistically analyzed using SPSS software., Results: The results show that kombucha compared with the green tea extract caused more (1.2 fold) early apoptosis induction and G0/G1 phase arrest. Moreover, kombucha increased the expression levels of p21, p53, and B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein genes (2, 2.5, and 1.5 fold, respectively) while it decreased Bcl-2 gene expression level (5-8 fold) compared with doxorubicin alone. Combination of kombucha with doxorubicin shows 2-fold increased G0/G1 phase compared with the doxorubicin treatment., Conclusion: This result indicated that kombucha caused boosted anticancer activity of doxorubicin agent. These findings suggest that kombucha may be has an assistor and useful role in colorectal cancer treatment align with chemotherapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Education and Health Promotion.)

The drastic decrease in estrogen levels in menopausal women can elevate bone resorption and osteoporosis. Cornus mas extract (C. mas extract) is a potential candidate for treating menopausal-related bone complications because of its phytoestrogen and anti-inflammatory contents. It was an interventional double-blind placebo-controlled randomized study. Eighty-four women aged 45-60 years old were randomly allocated to either the extract group receiving 3 capsules of 300 mg C. mas extract or the placebo group receiving 3 capsules of 300 mg of starch powder per day for 8 weeks. Then, venous blood was used to measure bone-specific alkaline phosphatase (BAP), osteocalcin (OC), C-terminal telopeptide (TC) as well as serum levels of PTH and hsCRP. Our results indicated the decrease in alkaline phosphatase, PTH, and as an inflammation biomarker, hsCRP, between two groups at the end of the study. No statistically significant difference was observed in telopeptide C, osteocalcin, and calcium between the placebo and extract groups after 8 weeks of intervention. In conclusion, the results indicate that the C. mas extract supplement of 900 mg/day may decrease levels of BAP, PTH, and hsCRP. However, this intervention had no beneficial effect on OC and TC in healthy postmenopausal women., (© 2021 John Wiley & Sons Ltd.)

Background: Several mechanisms have been proposed for the effect of vitamin E on weight loss. Yet various interventional studies with wide ranges of doses and durations have reported contradictory results., Methods: Cochrane Library, PubMed, Scopus, and Embase databases were searched up to December 2020. Meta-analysis was performed using random-effect method. Effect size was presented as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was evaluated using the I 2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta regression analyses was conducted., Results: A total of 24 studies with 33 data sets were included. There was no significant effect of vitamin E on weight (WMD: 0.15, 95% CI: -1.35 to 1.65, P = 0.847), body mass index (BMI) (WMD = 0.04, 95% CI: -0.29 to 0.37, P = 0.815), and waist circumference (WC) (WMD = -0.19 kg, 95% CI: -2.06 to 1.68, P = 0.842), respectively. However, subgroup analysis revealed that vitamin E supplementation in studies conducted on participants with normal BMI (18.5-24.9) had increasing impact on BMI (P = 0.047)., Conclusion: There was no significant effect of vitamin E supplementation on weight, BMI and WC. However, vitamin E supplementation might be associated with increasing BMI in people with normal BMI (18.5-24.9)., Competing Interests: Conflicts of interest All authors declared no conflicts of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Resveratrol is a phytochemical with anti-angiogenic, anti-inflammatory, and antioxidant properties. The present study has evaluated the effect of resveratrol on the expression of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β) and matrix metalloproteinase-9 (MMP-9) as factors related to endometriosis progression. Thirteen eutopic (EuESCs) and 8 ectopic (EESCs) endometrial stromal cells from women with endometriosis and 11 control endometrial stromal cells (CESCs) were treated with resveratrol (100 µM) for 6, 24 and 48 h. The gene and protein expression levels of VEGF, TGF-β, and MMP-9 were measured using real-time PCR and ELISA methods, respectively. Results showed that the basal gene and protein expression of VEGF and MMP-9 were higher in EESCs compared to EuESCs and CESCs (P < 0.01 to  < 0.001 and P < 0.05 to  < 0.01 respectively). Also, resveratrol treatment decreased the gene and protein expression of VEGF and MMP-9 in EuESCs, EESCs and CESCs (P < 0.05 to  < 0.01 and P < 0.05 to  < 0.01 respectively) and gene and protein expression of TGF-β in EESCs and EuESCs (P < 0.05 to  < 0.01). The effect of resveratrol in reduction of VEGF gene expression was statistically more noticeable in EESCs compared to EuESCs and CESCs (P < 0.05). According to the findings, resveratrol may ameliorate endometriosis progression through reducing the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells (ESCs).

Background: Food store measurement is important for planners and policy makers to improve unhealthy stores towards healthy stores. This review aimed to outline the concepts and measures development of checklists that assess food store environment in urban communities., Methods: The search was carried out in PubMed, Embase, Web of Science and Scopus as well as reference lists of included studies for obtaining published articles between 1990 up to the date of search (30 June 2017). Eligibility criteria attempted to capture peer-reviewed articles aimed at development and validation of checklists for assessing food stores., Results: From 3,862 records, 24 studies were included in this review. Findings showed constructs included in the instruments were availability (n=22); price (n=22); quality of fresh foods (n=13); promotion (n=6); product placement (n=6); advertisement (n=5); shelf space (n=3); display (n=3); store features or characteristics (n=2); marketing (n=2); accessibility; nutrition information; visibility; food variety; signage. There are differences on the conceptual definition of each constructs across the checklists. Only half of studies pursued fully systematic steps for the measures development., Conclusion: Consensus for definition of constructs of food store measurement is necessary. Besides, the development of the measures of checklists needs to be done by high-quality methods., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2021 Zerafati-Shoae et al. Published by Tehran University of Medical Sciences.)

Supplementation with saffron helps improve antioxidant status. Oxidative stress plays an important role in ulcerative colitis (UC). The present study aimed to investigate the effect of saffron supplementation on disease severity and Oxidative/Antioxidant factors in patients with UC. This randomized double-blinded study was conducted on 80 mild to moderate UC patients. Participants were randomly divided into intervention (100 mg saffron/daily) and placebo (100 mg maltodextrin/daily) groups. Of all the participants, 75 completed the study. After 8 weeks, there were significantly increased in the mean score of simple clinical colitis activity index questionnaire (3.83 ± 1.78 to 3 ± 1.60, p = .004), the serum levels of total antioxidant capacity (2.68 ± 0.90 to 2.79 ± 0.87, p = .016), superoxide dismutase (60.69 ± 9.59 to 66.30 ± 10.79, p = .009) and glutathione peroxidase (22.05 ± 14.27 to 29.67 ± 17.97, p = .011) in patients received saffron compared to the placebo group. Whereas, there was no significant difference in serum levels of malondialdehyde between the two groups. Finally, dietary saffron as an alternative therapy may effective in improving antioxidant factors and reducing the severity of disease in UC patients., (© 2020 John Wiley & Sons Ltd.)

Rheumatoid arthritis (RA) is an autoimmune disease associated with inflammation. In this trial, we aimed to investigate the Immunomodulatory effect of hydroalcoholic extract of black barberry on immune mediators in patients with active rheumatoid arthritis. In this randomized, double-blind, placebo-controlled clinical trial, 80 women with active RA were randomly assigned into two groups of two capsules, each containing 1,000 mg black barberry extract (n = 40) or maltodextrin placebo (n = 40) daily for 12 weeks. Demographic indices, physical activity, dietary intake, and disease activity were investigated using suitable questionnaires. Concentration of cytokines IL-2, IL-4, IL-10, and IL-17 in blood sample were measured using PBMC method. Statistical analysis was performed using SPSS (version 22). At baseline, there were no differences between the two groups in terms of demographic indices, physical activity, and dietary intake (p > .05). Black barberry supplementation reduced the severity of RA. It showed no significant effect on IL-2 and IL-4 cytokines (p > .05). IL-17 levels decreased significantly after the intervention within the black barberry group, while IL-10 had a significant increase in this group (p < .05). Barberry extract may reduce inflammatory and increase anti-inflammatory cytokines in RA, and stimulates the immune response by increasing Th2 production., (© 2020 John Wiley & Sons Ltd.)

Background: Using chemical agents to cure diabetes mellitus and its complications may be accompanied by complications. New natural agents, such as spirulina and chlorella, could be used as alternative choices in this case., Methods: 65 male Wistar rats were allocated to 5 groups: A (healthy control), B (diabetic rats with a normal diet), C (diabetic rats supplemented with 50 g/kg/day spirulina), D (diabetic rats supplemented with 50 g/kg/day chlorella) and E (diabetic rats supplemented with 25 g/kg/day chlorella and 25 g/kg/day spirulina). After 21 days, wounds were inflicted on the back of rats. Assessment of blood sugar (BS), high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor (VEGF), granulation tissue formation, vascularization, epithelialization, and percentage of wound healing were determined along with macroscopic examinations., Results: The microscopic changes at days 3, 7, 14, and 21 showed significant evidence of improved angiogenesis, epithelial proliferation, and granulation tissue formation in the spirulina and chlorella treated rats compared with the controls (p˂0.05). Both spirulina and chlorella treatments of diabetic rats resulted in a significant reduction in BS and weight (p˂0.05), but VEGF and hs-CRP levels did not significantly change ( p  > 0.05). Percentage of wound healing was 100% on day 21 in all groups, except the control group B (97.8 ± 1.15%)., Conclusions: The results of this study showed that supplementation with spirulina and chlorella alone and combined could improve wound healing indices in diabetic rats and could therefore be recommended for the management of diabetic ulcer., Competing Interests: Competing interestsNone., (© Springer Nature Switzerland AG 2021.)

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by oxidative stress and inflammation in the hepatocytes. Saffron and its constituents are reported to have several properties such as anti-inflammatory and anti-diabetic effects., Materials and Methods: In a randomized double-blind placebo-controlled trial with two parallel groups including 76 eligible men and female patients with NAFLD aged 18-65, recruited from Hazrat Rasul Akram Hospital in Tehran, Iran. NAFLD was defined by a Gastroenterologist based on the American Gastrointestinal and Liver Association standards. Participants were randomly assigned to two groups receiving daily supplementation of either one tablet of 100 mg saffron (n = 38) or one placebo (n = 38) for 12 weeks. The primary outcome was high sensitive C-reactive protein (hs-CRP) and secondary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA), total anti-oxidant capacity (TAC), leptin, adiponectin, anthropometric, and body composition Both groups were assigned similar diet and physical activity., Results: In the treatment group, significant decreases in hs-CRP (-1.80 ng/ml, 95% CI = -2.97, -0.63, p = .032), leptin (-0.27 ng/ml, 95% CI = -0.65, -0.10, p = .040), MDA (-1.01 ng/ml, 95% CI = -1.89, -0.14, p = .023) and significant increase in TAC (0.34 μmol/L, 95% CI = 0.08, 0.61, p = .011) were observed compared to the placebo group. However, there were no significant changes in serum alanine aminotransferase, AST, TNF-α, body composition, and anthropometric indexes (p > .05)., Conclusion: In the present study, 12 weeks of 100 mg of saffron supplementation indicated beneficial effects on serum levels of some inflammatory, oxidative stress, and adipokines biomarkers but it had no significant effect on serum concentrations of liver enzymes, anthropometric, and body composition measurements., (© 2020 John Wiley & Sons, Ltd.)

This study aimed to evaluate the clinical efficacy of probiotic and prebiotic supplementation on the metabolic parameters, liver enzymes, and inflammation in patients with nonalcoholic fatty liver disease (NAFLD). In this study, patients with NAFLD were assigned to receive either probiotic capsule + placebo of prebiotic (probiotic group), oligofructose + placebo of probiotic (prebiotic group), or placebo of probiotic + placebo of prebiotic (control group) for 12 weeks. All participants followed a weight loss diet and physical activity recommendation during intervention. Anthropometric measurements decreased in all three groups, but there was no significant difference among groups. Probiotic supplementation was able to decrease triglyceride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and alkaline phosphatase compared to control group. The serum levels of triglyceride, total and low-density lipoprotein cholesterol, ALT, AST, and GGT differed significantly in prebiotic group in comparison to the placebo. High-sensitive C-reactive protein significantly decreased within all groups; however, there was no significant difference among groups after intervention. Probiotic and prebiotic may be beneficial in improving liver enzymes and lipid profile in patients with NAFLD., (© 2020 Institute of Food Technologists®.)

Background: Studies have shown that evening primrose oil (EPO) supplementation might be effective in improving lipid profile, however, the results are inconsistent. This study was performed to determine the direction and magnitude of the EPO effect on the lipid profile., Methods: PubMed, Scopus, Cochrane Library, Embase and Web of Science databases and Google Scholar were searched up to September-2019. Meta-analysis was performed using the random-effects model. Lipid profile including high-density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) was considered as the primary outcome., Results: A total of 926 articles were identified through database searching, of which, six RCTs were included in the meta-analysis. There were six studies on HDL, TC, and TG and four studies on LDL. EPO supplementation had no significant effect on TC, TG, LDL, and HDL. However, in subgroup analysis, a significant reduction in TG at a dose of ≤4 g/day (weighted mean difference [WMD] = -37.28 mg/dl; 95% CI: -73.53 to -1.03, p = .044) and a significant increase in HDL in hyperlipidemic subjects (WMD = 5.468 mg/dl; 95% CI: 1.323 to 9.614, p = .010) was found., Conclusion: Oral intake of EPO at a dose of ≤4 g/day significantly reduces serum TG levels and significantly increases HDL levels in hyperlipidemic subjects., (© 2020 John Wiley & Sons, Ltd.)

Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease. Our study aimed to determine the effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active RA. In this randomized, double-blind, placebo-controlled trial, 66 women older than 18 years old received 100 mg/day either saffron supplement in the intervention group (n = 33) or matched placebo in the placebo group (n = 33) for a period of 12 weeks. Sixty-one patients (30 in the control and 31 in the saffron group) remained for the final analysis. No adverse effects were reported by the patients. Saffron supplementation significantly decreased the number of tender (-1.38 ± 1.66 vs. 0.10 ± 0.40, p < .001) and swollen (-2.12 ± 2.34 vs. 0.63 ± 2.79, p < .001) joints, pain intensity based on visual analogue scale (-18.36 ± 15.07 vs. -2.33 ± 5.04), p < .001), and disease activity score (DAS28) (-0.75 ± 0.67 vs. 0.26 ± 0.77, p < .001) at the end of intervention between the two groups and in saffron group compared with baseline values. Physician Global Assessment (p = .002) and erythrocyte sedimentation rate were significantly improved after intervention (24.06 ± 12.66 vs. 32.00 ± 14.75, p = 0.028). High-sensitivity C-reactive protein reduced at the end of the intervention in the saffron group compared with baseline values (12.00 ± 7.40 vs. 8.82 ± 7.930, p = .004). Tumor necrosis factor alpha, interferon gamma, and malondialdehyde were decreased, and total antioxidant capacity were increased, but their differences between the two groups were not significant (p > .05). According to the results, saffron supplements could positively and significantly improve clinical outcomes in RA patients., (© 2020 John Wiley & Sons, Ltd.)

Objectives: Since, the main cause of death in Rheumatoid arthritis (RA) patients is the presence of type 2 diabetes, abnormal increase in blood lipids, blood pressure and obesity, the aim of this study was to assess the effects of Barberry on the anthropometric indices and metabolic profile in patients with RA., Design: present study was a double-blinded, placebo-controlled randomized clinical trial., Setting: 70 active RA patients were randomly allocated into intervention or placebo group INTERVENTION: Participants received 6 capsules of 500 mg barberry extract or placebo for 3 months., Main Outcome Measures: Serum levels of fasting blood sugar (FBS), triglyceride (TG), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), systolic and diastolic blood pressure and anthropometric factors were assessed at baseline and at the end of the trial., Results: The results of intervention on 62 patients showed that weight, BMI, and conicity index increased in both groups, but this was significant only in the placebo group (p < 0.001). Waist and hip circumference were decreased in the intervention group and increased significantly in the placebo group (p < 0.001). Body fat percent (p = 0.04), LDL-C (p = 0.05) and SBP (p = 0.02) significantly were decreased in the intervention group. The results showed a significant decrease in body fat percent (p = 0.05), hip circumference (p < 0.001), FBS (p = 0.03) and HDL-C (p = 0.03) in the intervention group compared to the placebo., Conclusions: Overall, the results of this study demonstrated that the extract of Berberis Integerrima had beneficial effects on metabolic profile and anthropometric indices in RA patients., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Rheumatoid arthritis (RA) is a chronic autoimmune and inflammatory disease that affects the joints and consequently leads to the destruction of cartilage and bone lesions. Traditionally, ginger has been consumed in treatment of osteoarthritis, joint and muscle pain, neurological diseases, and inflammation of gums, tooth pain, asthma, stroke, diabetes, and constipation. The aim of this study was to determine the effect of ginger on some immunological and inflammatory markers in patients with rheumatoid arthritis. Methods: In this study, which was performed during 2013-2016, 66 patients with active rheumatoid arthritis who referred to the rheumatology clinic at Shariati hospital were en-rolled. Patients were randomly divided into 2 groups: one group consumed 1.5 gr ginger per day, and the other group took roasted wheat flour (placebo), respectively. To determine the effect of confounding factors on the findings of the study, questionnaires for nutrient intake, physical activity, and medication were filled, and BMI was measured. For each participant, at the beginning and end of the study, Serum hs-CRP and mRNA levels of IL-1β, IL-2 and TNF-α were determined by ELISA and Quantitative Real Time PCR, respectively. Statistical analysis was performed using SPSS software. Significance level was set at p<0.05. Results: Results of the study showed ginger powder supplementation caused a significant decline in CRP (p=0.050) and IL-1β mRNA level (p=0.021). TNFα mRNA levels reduced in ginger group compared to placebo groupalthough the difference was not significant between the 2 groups (p=0.093). Ginger had no effects on IL2 gene expression. Conclusion: This study showed that ginger reduces inflammatory factors hs-CRP and IL-1β gene expression in patients with active RA and it seems that ginger can improve the inflam-mation in the patients., (© 2019 Iran University of Medical Sciences.)

Background: Rheumatoid Arthritis (RA) is an autoimmune disease. Antioxidants intake and body antioxidants status are important in patients with RA. The aim of this study was to investigate the association between dietary intake of some antioxidant micronutrients with some inflammatory and antioxidant markers in patients with active rheumatoid arthritis and comparison with Recommended Dietary Allowance (RDA). Materials and Methods: In this cross-sectional study, eighty-seven patients with active rheumatoid arthritis were included. Dietary antioxidants intake was measured using 24-hour recall questionnaire and food record (3 days). Blood levels of inflammatory and antioxidant markers were determined by laboratory tests. The association between intake of antioxidants with inflammatory and antioxidant markers, and also with RDA were determined using Paired-Samples t-test and Pearson correlation by SPSS software. Results: The findings showed that intakes of vitamin E, zinc, and magnesium in patients were significantly lower and intakes of copper and selenium were significantly higher than RDA (P < 0.05). Significant negative correlations were observed between vitamin A intake with PGE2 [R = -0.31], vitamin C intake with IL-1β [R = -0.25], zinc intake with PGE2 [R = -0.30], IL-2 [R = -0.23], and the activity of glutathione reductase enzyme [R = -0.21], magnesium intake with PGE2 [R = -0.24], IL-1β [R = -0.23] and IL-2 [R = -0.25], and selenium intake with PGE2 [R = -0.21] (P < 0.05). Also, significant positive correlations were observed between intakes of vitamin E and copper with catalase enzyme activity [R = 0.22 and R = 0.21 respectively] (P < 0.05). Conclusion: Some of the antioxidant micronutrients play important roles in the reduction of inflammatory conditions and improve the function of antioxidant enzymes in patients with rheumatoid arthritis.

Menopause, which occurs following a declined ovarian activity and reduced estrogen levels, can lead to long-term changes in lipid and glycemic profiles and increases the risk of cardiovascular disease and osteoporosis. Cornelian cherry (Cornus mas) is rich in phytochemicals and antioxidants, which appears to be useful in reducing the postmenopausal complications. This interventional, double-blinded, randomized clinical trial carried out on 84 menopaused women aged 45-60 years old. They were randomly divided into two groups. The treatment group received three capsules of 300 mg of Cornus mas extract (CME), and control group received three capsules of 300 mg of starch powder per day for 8 weeks. Then, BMI, waist circumference, glycemic indices, lipid profile, serum apoproteinase, apoprotein B100, fibrinogen, and leptin were measured. The dietary intakes were evaluated using 24-hr dietary recall questionnaire. The consumption of CME in comparison with the control group resulted in a significant reduction in weight, body mass index, waist circumference, LDL to HDL ratio, total cholesterol to HDL ratio, and fibrinogen. There was also a significant increase in HDL and ApoA1 levels in the treatment group. Furthermore, there was a significant decrease in BMI, waist circumference, fasting insulin, and insulin resistance index after 8 weeks of using CME. Summing up the results, it can be concluded that CME can have possible effects on decreasing BMI, waist circumference, and improving some aspects of lipid profile and glycemic indices in postmenopausal women., (© 2019 John Wiley & Sons, Ltd.)

Recently, obesity has become a common worldwide concern. Leptin, as an adipocytokine, plays a major role in the etiology of obesity. Prior studies have demonstrated that zinc potentially affects serum leptin levels. However, clinical trials carried out in this regard are not consistent. Therefore, current meta-analysis was conducted to ascertain the actual effect of zinc supplementation on serum leptin levels in adults. Databases of PubMed, SCOPUS, and Google Scholar were methodically searched to identify relevant articles up to April 2018. Clinical trials that examined the effect of zinc supplementation on serum leptin concentrations as outcome variables in human adults were included. The mean difference (SD) of leptin changes in the intervention and placebo groups were used to calculate the overall effect size. Totally, 663 articles were identified, of which 6 studies were eligible randomized controlled trials (RCTs) with 7 treatment arms. The analysis suggested that zinc supplementation exerts no significant effect on overall serum leptin (WMD: 0.74 ng/ml; 95% CI: -1.39 to 2.87, p=0.49). Nevertheless, sex and duration of intervention seemed to impact the extent of zinc's influence. In trials with female subjects, zinc consumption led to a significant decrease in serum leptin level (WMD: -1.93 ng/ml; 95% CI: -3.72 to -0.14, p=0.03) as well as trials that lasted for more than 6 weeks (WMD: -1.71 ng/ml; 95% CI: -3.07 to -0.35, p=0.01), in comparison to the control group. Zinc supplementation did not significantly improve leptin concentrations, but it may result in a decreased circulating leptin level in studies with a duration of more than 6 weeks especially among females., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Microalbuminuria and hypertension are the risk factors for diabetic nephropathy, and increased levels of liver enzymes are prevalent among diabetic patients. The aim of this research was to examine the effects of Crocus sativus supplementation on nephropathy indices, liver enzymes, and blood pressure in patients with type 2 diabetes (T2D)., Materials and Methods: This placebo-controlled, randomized clinical trial was performed among 80 T2D patients. Subjects were randomly assigned to either Crocus sativus (n = 40) or placebo (n = 40) groups and treated with C. sativus and or placebo for 12 weeks, respectively. Alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum urea, creatinine, 24-hr urine albumin, systolic blood pressure (SBP), diastolic blood pressure (DBP), physical activity, and dietary intakes were measured and blood samples were taken at baseline and after the 12‑week intervention to assess the differences between the two groups., Results: C. sativus supplementation compared with the placebo resulted in a significant reduction of SBP (P<0.005). However, changes in other indices including liver enzymes, serum creatinine, serum urea, and 24-hr urine albumin, and DBP were not significantly different between the two groups (p>0.05). Also, no significant changes in dietary intakes and physical activity were seen between the two groups., Conclusion: This report shows that daily supplementation with 100 mg C. sativus powder improved SBP. However, it did not considerably improve DBP, nephropathy indices and liver functions in T2D patients after 12 weeks of administration., Competing Interests: The authors declare no conflict of interests.

Objective: Rheumatoid Arthritis (RA) is an autoimmune disease. The aim of this study was to investigate the effect of ginger supplementation on the expression of some immunity and inflammation intermediate genes in patients who suffer from RA., Methods: In this randomized double-blind placebo-controlled clinical trial, seventy active RA patients were allocated randomly into two groups who either received 1500 mg ginger powder or placebo daily for 12 weeks. Disease activity score and gene expression of NF-κB, PPAR-γ, FoxP3, T-bet, GATA-3, and RORγt as immunity and inflammation intermediate factors were measured using quantitative real-time PCR before and after the intervention., Results: After the intervention, FoxP3 genes expression increased significantly within ginger group and between the two groups (P-value = 0.02). Besides, T-bet and RORγt genes expression decreased significantly between the two groups (P-value < 0.05). In ginger group, PPAR-γ genes expression increased significantly (P-value = 0.047) but the difference between the two groups wasn't statistically significant (P-value = 0.12). The reduction in disease activity score was statistically significant within ginger group and between the two groups after the intervention., Conclusion: It seems that ginger can improve RA by decreasing disease manifestations via increasing FoxP3 genes expression and by decreasing RORγt and T-bet genes expression., (Copyright © 2019. Published by Elsevier B.V.)

Resveratrol, a phytoalexin polyphenol, has antiproliferative, antiangiogenic, anti-inflammatory, and antioxidant properties. The present study has assessed the effect of resveratrol treatment on the expression of insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) in endometrial stromal cells (ESCs) from women with and without endometriosis. Endometrial tissues were obtained from 40 endometriotic patients and 15 nonendometriotic control women. After the enzymatic digestion, 13 eutopic ESCs (EuESCs), 8 ectopic ESCs (EESCs), and 11 control ESCs (CESCs) were treated with resveratrol (100 μM) for 6, 24, and 48 hr. The gene and protein expressions of IGF-1 and HGF were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. Results showed that resveratrol treatment decreased significantly the gene expression of IGF-1 and HGF in EuESCs, EESCs, and CESCs (p < 0.05). The effect of resveratrol treatment on the reduction of IGF-1 gene expression was statistically more noticeable in EESCs compared with CESCs (p < 0.05). Also, in the case of HGF gene expression, the reducing effect of resveratrol treatment was statistically more considerable in EESCs compared with EuESCs and CESCs (p < 0.05 and p < 0.01, respectively). The IGF-1 and HGF protein production decreased significantly in EuESCs and EESCs (p < 0.05) but not in CESCs. These findings suggest that resveratrol treatment could reduce the expression of IGF-1 and HGF in ESCs especially in EESCs, which play a pivotal role in disease progression., (© 2019 John Wiley & Sons, Ltd.)