Evaluation of apoptosis and angiogenesis in ectopic and eutopic stromal cells of patients with endometriosis compared to non-endometriotic controls

Background: Endometriosis is a chronic, painful, and inflammatory disease characterized by extra-uterine growth of endometrial tissues. Increased angiogenesis and resistance to apoptosis have been suggested to be involved in pathogenesis and development of endometriosis. The objective of this study was to examine apoptosis potential and angiogenesis contribution of eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells in patients with endometriosis compared to endometrial stromal cells from non-endometriotic controls (CESCs). Methods: Stromal cells were isolated by enzymatic digestion of ectopic (n = 11) and eutopic (n = 17) endometrial tissues from laparoscopically-confirmed endometriotic patients. Endometrial stromal cells of 15 non-endometriotic patients served as control. Following cell characterization by immunofluorescent staining and flow cytometry using a panel of antibodies, the total RNA was isolated from the cultured cells, and analyzed for the expression of genes involved in apoptosis (Bcl-2, Bcl-xL, Bax, and caspase-3) and angiogenesis vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF) by Real-time PCR. Results: Significantly higher gene expression levels of Bcl-2 and Bcl-xL were found in EESCs compared with EuESCs and CESCs (p < 0.01). The gene expression of Bax in EESCs, EuESCs, and CESCs was not statistically significant. Furthermore, EuESCs exhibited a significantly lower caspase-3 gene expression compared with CESCs (p < 0.01) or EESCs (p < 0.05). Regarding angiogenesis, VEGF-A gene expression in EESCs (p < 0.001) and EuESCs (p < 0.05) were significantly higher compared with those of CESCs. EESCs exhibited a significantly higher HGF gene expression compared with EuESCs (p < 0.05). Conclusions: These findings suggest reduced propensity to apoptosis and increased angiogenesis potential of EESCs, which may be involved in pathogenesis of endometriosis. © 2020 The Author(s)

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. © 2020, Iranian Journal of Public Health. All rights reserved

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. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd

The effects of resveratrol on the expression of VEGF, TGF-β, 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-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). © 2021, The Author(s)

Effect of fish oil on circulating asymmetric dimethylarginine and adiponectin in overweight or obese patients with atrial fibrillation

Obesity and adipose-derived peptides might be involved in the pathogenesis of atrial fibrillation (AF). Adiponectin plays a major role in the modulation of several metabolic pathways, and asymmetric dimethylarginine (ADMA) has been suggested to be predictive of AF and associated adverse events. The aim of this study was to investigate the effect of fish oil supplementation on circulating adiponectin and ADMA in overweight or obese patients with persistent AF. In this randomized, double-blind, placebo-controlled trial, 80 overweight or obese (body mass index (BMI) � 25 kg/m2) patients with persistent AF were randomly assigned to two groups to receive either 2 g/day fish oil or placebo, for 8 weeks. Serum levels of adiponectin and ADMA, and anthropometric indexes were measured. This study showed that serum adiponectin concentrations increased significantly following fish oil supplementation compared with the placebo group (13.15 ± 7.33 vs. 11.88 ± 6.94 µg/ml; p =.026). A significant reduction was also observed in serum ADMA levels in the fish oil compared with the placebo group following the intervention (0.6 ± 0.13 vs. 0.72 ± 0.15 µmol/L; p =.001). The changes in serum adiponectin and ADMA concentrations remained significant after adjustments for baseline values, age, sex, and changes of BMI and waist circumference (p =.011 and p =.001, respectively). In conclusion, 8 weeks supplementation with fish oil increased serum adiponectin and decreased ADMA concentrations in overweight or obese patients with persistent AF. As adiponectin and ADMA are suggested to be involved in many pathways associated with AF, the current findings might be promising in the clinical management of this disease, an issue that needs further investigations. © 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc

Ruminant trans-fatty acids and risk of breast cancer: A systematic review and meta-analysis of observational studies

INTRODUCTION: Ruminant trans-fatty acids, especially cis9, trans11-conjugated linoleic acid (c9, t11-CLA) and trans11-18:1 vaccenic acid (t11-18:1 VA) appear to have anticarcinogenic activity against breast cancer in animal and in vitro experiments. However, the results remain inconsistent. We therefore conducted a systematic review and metaanalysis to assess the association of c9, t11-CLA, and t11-18:1 VA (intake or serum levels) with breast cancer risk. EVIDENCE ACQUISITION: Relevant studies were identified by a search of PubMed, OVID, SCOPUS and Google scholar databases through 25 May 2015. We included case-control and cohort studies that reported relative risk (RR) estimates with 95 confidence intervals (CIs) for the association between c9, t11-CLA and t11-18:1 VA intake or their serum levels and the risk of breast cancer. This meta-analysis was conducted according to the guidelines for the meta-analysis of observational studies in epidemiology. EVIDENCE SYNTHESIS: Three studies on c9, t11-CLA and t11-18:1 VA serum levels and t11-18:1 VA intake were evaluated in the systematic review only (narrative synthesis) and four studies (2 case-control and 2 cohort studies on c9, t11-CLA intake) were included in the meta-analysis (quantitative synthesis). The pooled RR for the highest vs lowest category of c9, t11-CLA intake was 0.94 (95 CI: 0.64-1.25) with evidence of heterogeneity (with 67, 533 participants, I2=78.3, P=0.003). Studies that could not be included in the quantitative syntheses were inconclusive. CONCLUSIONS: No association was found between c9, t11-CLA intake and breast cancer risk, but the number of studies identified was small. © 2016 Edizioni Minerva Medica

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. © 2017 Elsevier Masson SA

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. © 2017 Elsevier Masson SA

Sodium status and the metabolic syndrome: A systematic review and meta-analysis of observational studies

The prevalence of metabolic syndrome (MetS) has been greatly increased, worldwide. In recent years, investigators have proposed that sodium might contribute to the development of metabolic syndrome; however, the published data were conflicting. The present systematic review aimed to summarize the evidence from observational studies in this regard. We conducted a systematic search for relevant observational studies investigating the association between sodium status and MetS, published until June 2017 in electronic databases including PubMed, EMBASE, Scopus and Google Scholar. Summary effects were derived using random effects model. After screening the records, seventeen publications with 66,274 participants were eligible to be included in the systematic review and meta-analysis. The analysis revealed that subjects with MetS have significantly higher levels of sodium compared to healthy controls (Hedges' g = 0.21, 95 CI: 0.12, 0.29, I 2 = 68.6). Subgroup analyses revealed that the difference was significant when the sodium status was assessed using urinary sodium levels. The random effects meta-regression analysis also revealed that body sodium level increases with the number of MetS components. Furthermore, participants with highest dietary/urinary or serum sodium levels had 37 higher chance of developing MetS when compared with participants with the lowest sodium levels (OR = 1.37 95CI: 1.31, 1.42, I 2 = 86.9). The current meta-analysis revealed that higher sodium input into the body is directly associated with the likelihood of MetS. Prospective cohort studies and well-designed randomized clinical trials considering the effect of sodium restricted diets on the risk of MetS as an outcome are necessary to represent the causal association. © 2017, © 2017 Taylor & Francis Group, LLC