The effects of resveratrol on the expression of VEGF, TGF-ß, and MMP-9 in endometrial stromal cells of women with endometriosis.

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-ß (TGF-ß) 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-ß, 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-ß 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-ß, and MMP-9 in endometrial stromal cells (ESCs).

Resveratrol treatment reduces expression of MCP-1, IL-6, IL-8 and RANTES in endometriotic stromal cells.

Endometriosis is an inflammatory disease affecting reproductive-aged women. Immunologic disturbance, as well as inflammation, have crucial roles in the pathogenesis of endometriosis. In this study, we evaluated the effects of resveratrol treatment on expression of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), IL-8, and regulated upon activation, normal T cell expressed and secreted (RANTES) in endometrial stromal cells from patients with endometriosis compared with non-endometriotic controls. Thirteen eutopic (EuESCs) and nine ectopic (EESCs) endometrial stromal cells from endometriotic patients as well as eleven endometrial stromal cells from non-endometriotic controls (CESCs) were treated with resveratrol (100 µmol/L) or ethanol, and gene and/or protein expression of MCP-1, IL-6, IL-8 and RANTES was examined at 6, 24 and 48 hours following treatment in the cells from all origins. Resveratrol treatment significantly reduced gene and protein expression of MCP-1, IL-6, and IL-8 in EuESCs and EESCs compared with CESCs (P < .05-.001, P < .05-.001 and P < .05-<.01, respectively), and this reduction was more noticeable in EESCs than EuESCs (P < .05-<.001). Besides, resveratrol treatment significantly reduced RANTES protein expression in EESCs in all time intervals (P < .05). Resveratrol treatment significantly reduced the expression of MCP-1, IL-6, IL-8 and RANTES in EESCs.

The Effects of Resveratrol Treatment on Bcl-2 and Bax Gene Expression in Endometriotic Compared with Non-Endometriotic Stromal Cells.

BACKGROUND: We aimed to examine resveratrol effects on gene expression of Bcl-2, Bax and Bcl-2/Bax ratio in endometrial stromal cells derived from women with and without endometriosis. METHODS: Endometrial tissues were obtained from 40 endometriotic patients and 15 non-endometriotic controls undergoing laparoscopic surgery or hysterectomy in the gynecology ward of Rassoul Akram Hospital, Tehran, Iran from 2015 to 2017. After the enzymatic digestion, eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells from patients with endometriosis as well as endometrial stromal cells from non-endometriotic controls (CESCs) were treated with or without resveratrol (100 µM) and the levels of Bcl-2, Bax and Bcl-2/Bax gene expression ratio in the cells from all origins were examined at 6, 24 and 48 h post-treatment by real-time PCR. RESULTS: Resveratrol treatment increased Bcl-2 expression in CESCs at 24 and 48 h and in EuESCs at 48 h (P<0.05), but had no significant effects on the expression of this gene in EESCs. On the other hand, resveratrol treatment increased Bax expression in EuESCs at 6 h and decreased its expression in EESCs at 48 h (P<0.05). Regarding the Bcl-2/Bax gene expression ratio, resveratrol treatment increased Bcl-2/Bax gene expression ratio in CESCs and EuESCs at 48 h (P<0.01). However, this treatment had no significant differential effect on Bcl-2 and Bcl-2/Bax gene expression ratio between CESCs and EuESCs at 48 h. CONCLUSION: Resveratrol treatment significantly increased Bcl-2/Bax gene expression ratio in EuESCs and CESCs but had no significant effect in EESCs.

Adherence to the dietary approaches to stop hypertension (DASH) diet in relation to all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.

BACKGROUND: Although previous investigations have proposed an association between Dietary Approaches to Stop Hypertension (DASH)-style diet and lower mortality from chronic diseases, the exposure-response relationship is not clear. The present systematic review and meta-analysis aimed to explore the linear and non-linear dose-response association between adherence to the DASH diet and all-cause and cause-specific mortality. METHODS: Database search was performed in PubMed, Scopus, and EMBASE for prospective cohort studies investigating the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and risk of mortality. Summary hazard ratios (HRs) and 95% confidence intervals (CI) were estimated with the use of a random-effects model for the linear and nonlinear relationships. The two-stage hierarchical regression model was applied to test the potential non-linear dose-response associations. RESULTS: The inclusion criteria were met by 17 studies (13 publications). The scores reported for adherence to the DASH diet in different studies were converted to a conventional scoring method in which the adherence score might range between 8 to 40. The linear analysis revealed that summary HRs were 0.95 (95% CI: 0.94-0.96, I2 = 91.6%, n = 14) for all-cause, 0.96 (95% CI: 0.95-0.98, I2 = 82.4%, n = 12) for CVD, 0.97 (95% CI: 0.96-0.98, I2 = 0.00%, n = 2) for stroke, and 0.97 (95% CI: 0.95-0.98, I2 = 63.7%, n = 12) for cancer mortality per each 5-point increment of adherence to the DASH diet. There was also evidence of non-linear associations between the DASH diet and all-cause and cause-specific mortality as the associations became even more evident when the adherence scores were more than 20 points (P < 0.005). CONCLUSION: Even the modest adherence to the DASH diet is associated with a lower risk of all-cause and cause-specific mortality. The higher adherence to the diet also strengthens the risk-reducing association. REGISTRATION: This review was registered in the international prospective register of systematic reviews (PROSPERO) database (registration ID: CRD42018086500).

Higher frequency of circulating, but not tissue regulatory T cells in patients with endometriosis.

BACKGROUND: Endometriosis is one of the most common chronic gynecological disorders affecting women at reproductive age. Dysregulation of immune cells, including regulatory T (Treg) cells has contributed to the growth of ectopic lesion in patients with endometriosis. OBJECTIVE: The present study investigated the frequency of Tregs in peripheral blood and the expression of Foxp3 in eutopic and ectopic endometriotic tissues in women with and without endometriosis. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) and eutopic and ectopic endometriotic tissues were obtained from 23 endometriotic and 20 non-endometriotic control women. The frequency of Treg cells in PBMCs was measured using flowcytometry and the expression of Foxp3 in eutopic and ectopic endometriotic tissues was determined by real-time PCR, western blotting and immunohistochemistry. RESULT: The frequency of circulating Tregs was significantly higher in endometriotic patients compared with non-endometriotic controls (P < 0.01). The mRNA and protein expression of Foxp3 in eutopic and ectopic endometriotic tissues had no significant differences between the two study groups. CONCLUSION: Higher frequency of circulating Tregs in patients with endometriosis compared with controls may be considered as a compensatory mechanism to regulate the inflammatory condition in this disease.

Association between dietary intake of some antioxidant micronutrients with some inflammatory and antioxidant markers in active Rheumatoid Arthritis patients.

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-1ß [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-1ß [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.

Resveratrol reduces the expression of insulin-like growth factor-1 and hepatocyte growth factor in stromal cells of women with endometriosis compared with nonendometriotic women.

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.

The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis.

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.

Effect of turmeric on glycemic status, lipid profile, hs-CRP, and total antioxidant capacity in hyperlipidemic type 2 diabetes mellitus patients.

Diabetes mellitus is the most common metabolic disorder worldwide. This study examined the effect of turmeric supplementation on glycemic status, lipid profile, hs-CRP and total antioxidant capacity in hyperlipidemic type 2 diabetic patients. In this double-blind, randomized clinical trial, 80 hyperlipidemic type 2 diabetic patients were divided into turmeric (2,100 mg powdered rhizome of turmeric daily) and placebo groups for 8 weeks. Body weight, fasting plasma glucose, hemoglobin A1c (HbA1c), serum insulin, triglyceride (TG), total cholesterol, low density lypoprotein cholesterol (LDL-c), high density lypoprotein cholesterol, apolipoprotein A1, apolipoprotein B, high sensitivity C-reactive protein (hs-CRP), and total antioxidant capacity were measured before and after intervention. Statistical analysis was carried out using paired and independent t and chi-square tests. Seventy five patients completed the study. The turmeric group showed significant decreases in body weight, TG, and LDL-c compared with baseline (p value < 0.05). Body mass index, TG, and total cholesterol decreased significantly in the turmeric group compared with the placebo group (p value < 0.05). No significant changes were observed in other parameters between the two groups after intervention (p value < 0.05). Turmeric improved some fractions of lipid profile and decreased body weight in hyperlipidemic patients with type 2 diabetes. It had no significant effect on glycemic status, hs-CRP, and total antioxidant capacity in these patients.

Curcumin and endometriosis: Review on potential roles and molecular mechanisms.

Endometriosis, an estrogen-dependent inflammatory disease, is one of the most common chronic gynecological disorders affecting women in reproductive age. It is characterized by the presence of endometrial-like tissue outside the uterus. The exact pathophysiology of endometriosis is not still well-known, but the immune system and inflammation have been considered as pivotal factors in disease progression. Turmeric, an important spice all around the world, is obtained from the rhizomes of Curcuma longa, a member of the Zingiberaceae family. It has been used in the prevention and treatment of many diseases since ancient times. Curcumin is the principal polyphenol isolated from turmeric. Several evidences have shown the anti-inflammatory, antioxidant, anti-tumor, anti-angiogenesis, and anti-metastatic activities of curcumin. In this review, relevant articles on the effect of curcumin on endometriosis and possible molecular mechanisms are discussed.

Resveratrol and endometriosis: In vitro and animal studies and underlying mechanisms (Review).

Endometriosis is characterized by the existence of endometrial tissue and stroma exterior to the uterus. Despite the high prevalence, the etiology of endometriosis remains elusive. The search for the most promising compounds for treatment of endometriosis has led to the identification of resveratrol. Resveratrol, a plant-derived polyphenolic phytoalexin, demonstrates broad-spectrum health beneficial effects, including anti-proliferative, anti-inflammatory, antineoplastic and antioxidant. Because of these properties and its wide distribution in plants, resveratrol is proposed as a great potential to treat endometriosis. In animal models of endometriosis, resveratrol supplementation has displayed beneficial results as it decreased the number and volume of endometrial implants, suppressed proliferation, vascularization, inflammation, cell survival and increased apoptosis. On the other hand, resveratrol treatment in-vitro studies, reduced invasiveness of endometriotic stromal cells (ESCs) and suppressed their inflammatory responses. In this review, we will summarize the recent studies in in-vitro and animal studies on resveratrol and endometriosis.

Polyphenols and their effects on diabetes management: A review.

Background: Type 2 diabetes is a growing public health problem and is associated with increased morbidity and mortality. The worldwide prevalence of type 2 diabetes is rising. Polyphenols, such as flavonoids, phenolic acid, and stilbens, are a large and heterogeneous group of phytochemicals in plant-based foods. In this review, we aimed at assessing the studies on polyphenols and diabetes management. Methods: A literature search in the PubMed, EMBASE, Scopus, and ISI Web of Science databases was conducted to identify relevant studies published from 1986 to Jan 2017. Results: Several animal models and a limited number of human studies have revealed that polyphenols decrease hyperglycemia and improve acute insulin secretion and insulin sensitivity. The possible mechanisms include decrease in glucose absorption in the intestine, inhibition of carbohydrates digestion, stimulation of insulin secretion, modulation of glucose release from the liver, activation of insulin receptors and glucose uptake in insulin-sensitive tissues, modulation of intracellular signaling pathways, and gene expression. Conclusion: Growing evidence indicates that various dietary polyphenols may influence blood glucose at different levels and may also help control and prevent diabetes complication. However, we still need more clinical trials to determine the effects of polyphenols- rich foods, their effective dose, and mechanisms of their effects in managing diabetes.

The effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus.

OBJECTIVE: To assess the effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus. METHODS: In a double-blinded, placebo-controlled clinical trial, 70 type 2 diabetic patients were enrolled. They allocated randomly into ginger group and control group. They consumed 1600 mg ginger versus 1600 mg wheat flour placebo daily for 12 weeks. Serum sugar, lipids, CRP, PGE2 and TNFα were measured before and after intervention. RESULTS: Ginger reduced fasting plasma glucose, HbA1C, insulin, HOMA, triglyceride, total cholesterol, CRP and PGE2 significantly compared with placebo group (p < 0.05). There were no significant differences in HDL, LDL and TNFα between two groups (p > 0.05). CONCLUSION: Ginger improved insulin sensitivity and some fractions of lipid profile, and reduced CRP and PGE2 in type 2 diabetic patients. Therefore ginger can be considered as an effective treatment for prevention of diabetes complications.