Use of placental-derived mesenchymal stem cells to restore ovarian function and metabolic profile in a rat model of the polycystic ovarian syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disturbance that affects many women worldwide and is characterized by chronic anovulation, hyperandrogenism, and ovarian dysfunction. Placenta-derived mesenchymal stem cells (PDMSCs) are derived from the placenta and have advantages over other sources of MSCs in terms of availability, safety, and immunomodulation. MATERIALS AND METHODS: In this experimental study, twenty female Wistar rats were assigned to four groups (n = 5) including control, sham, PCOS, and PCOS+PDMSCs groups. Then, PCOS was induced in the rats through administering letrozole for 21 days. PDMSCs (1 × 106 cells) were injected through the tail vein. Fourteen days after the cell infusion, evaluation was performed on the number of healthy follicles, corpus luteum, and cystic follicles as well as the levels of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), fasting blood glucose, fasting insulin, and insulin resistance. Moreover, the serum levels of cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured. Liver function was also determined by the evaluation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. RESULTS: The number of corpus luteum and primordial, primary, secondary, and antral follicles was significantly elevated in the PCOS+PDMSCs group compared to the PCOS group. However, the number of cystic follicles significantly decreased in the PCOS+PDMSCs group. The LH and testosterone levels also decreased significantly, while FSH levels increased significantly in the PCOS+PDMSCs group. The levels of fasting blood glucose, fasting insulin, and insulin resistance notably decreased in the PCOS+PDMSCs group. Moreover, the lipid profile improved in the PCOS+PDMSCs group along with a significant decrease of cholesterol, LDL, and TG and an increase in HDL. The PCOS+PDMSCs group exhibited marked decreases in the AST and ALT levels as well. CONCLUSION: The results of this study suggest that PDMSCs are a potential treatment option for PCOS because they can effectively restore folliculogenesis and correct hormonal imbalances, lipid profiles and liver dysfunction in a rat model of PCOS. However, further research is needed to establish the safety and effectiveness of PDMSCs for treating PCOS.

The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis.

BACKGROUND: To our knowledge, data on the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis are limited. This study was conducted to determine the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 18-40 years old) with endometriosis. Participants were randomly allocated into two groups (30 participants each group) to receive either 50,000 IU vitamin D or placebo each 2 weeks for 12 weeks. RESULTS: Vitamin D supplementation significantly decreased pelvic pain (ß - 1.12; 95% CI, -2.1, -0.09; p=.03) and total-/HDL-cholesterol ratio (ß - 0.29; 95% CI, -0.57, -0.008; p=.04) compared with the placebo. Moreover, vitamin D intake led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (ß - 0.64 mg/L; 95% CI, -0.97, -0.30; p<.001) and a significant increase in total antioxidant capacity (TAC) (ß 47.54 mmol/L; 95% CI, 19.98, 75.11; p=.001) compared with the placebo. CONCLUSIONS: Overall, our study demonstrated that vitamin D intake in patients with endometriosis resulted in a significant improvement of pelvic pain, total-/HDL-cholesterol ratio, hs-CRP and TAC levels, but did not affect other clinical symptoms and metabolic profiles.

Babu and Magon uterine closure technique during cesarean section: A randomized double-blind trial.

AIM: We compared the effectiveness of the Babu and Magon uterine closure technique and unlocked double-layer uterine closure on the integrity and thickness of the uterine scar. METHODS: A randomized double-blind trial was performed at Hazrat-e Rasoul -e-Akram Hospital, Tehran, Iran, from March 2018 to December 2019, in 72 pregnant women who were candidates for cesarean section for the first time. Women were randomly assigned to the Babu and Magon uterine closure technique (intervention group, n = 34) or double-layer closure of the uterine incision (control group, n = 38). The primary outcome of the study was the frequency of myometrial defects at the site of the scar (niche), and a large niche. Secondary outcomes, including the time taken for uterine closure and postpartum hemorrhage (early and late), were compared between groups. RESULTS: Adjacent myometrium thickness (AMT) between the two groups was not statistically significant. A niche was reported in 23.5% (8/34) and 50% (19/38) of women in the intervention and controls, respectively (p = 0.02). A large niche was reported in 2.9% (1/34) and 23.7% (9/38) of women in the intervention and controls, respectively (p < 0.01). The duration of uterine closure was not statistically significant between the two groups. Hemoglobin levels did not differ significantly between groups during the first 24 h post-surgery. CONCLUSION: The results of the study showed that the technique of uterine closure is one of the main potential determinants of myometrial healing. The Babu and Magon uterine closure technique seems to lead to tissue alignment during suturing and consequently cause better myometrial healing, although this issue calls for well-founded longer studies of appropriate design.

The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: Basic science and new insights based on gene expression.

Endometriosis is a frequent and chronic illness in young women which could be defined by the existence of endometrial stroma and glands outside of the normal site of the lining of the uterus. It has painful symptoms. The advanced stage of endometriosis may lead to gynecological malignancies, such as ovarian cancer, and other complications, including infertility. However, its exact physiopathology is not well known. Recent studies have shown the possible roles of inflammation along with oxidative stress. Additionally, angiogenesis and apoptosis dysregulation contribute to endometriosis pathophysiology. Therapeutic strategies and continuing attempts, to conquer endometriosis should be done regarding molecular signaling pathways. Thus, the present review summarizes current studies and focuses on molecular mechanisms.

Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study was conducted to evaluate the effects of vitamin D supplementation on the recurrence and metabolic status of patients with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). METHODS: This randomized, double-blind, placebo-controlled trial was carried out among 58 women diagnosed with CIN2/3. Participants were randomly assigned into 2 groups to receive either 50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months. RESULTS: The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly decreased fasting plasma glucose (-7.8 ± 9.2 vs. -1.1 ± 8.6 mg/dL, p = 0.006) and insulin levels (-3.2 ± 4.8 vs. -0.9 ± 3.4 µIU/mL, p = 0.03), and significantly increased quantitative insulin sensitivity check index (0.01 ± 0.02 vs. 0.002 ± 0.01, p = 0.02) compared with the placebo. Additionally, there was a significant decrease in high-sensitivity C-reactive protein (-815.3 ± 1,786.2 vs. 717.5 ± 1,827.3 ng/mL, p = 0.002) and a significant increase in total antioxidant capacity (113.4 ± 137.4 vs. -53.7 ± 186.7 mmol/L, p < 0.001) following the supplementation of vitamin D compared with the placebo. CONCLUSIONS: Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence.

The effects of coenzyme Q10 supplementation on gene expression related to insulin, lipid and inflammation in patients with polycystic ovary syndrome.

OBJECTIVE: This research was conducted to assess the effects of coenzyme Q10 (CoQ10) intake on gene expression related to insulin, lipid and inflammation in subjects with polycystic ovary syndrome (PCOS). METHODS: This randomized double-blind, placebo-controlled trial was conducted on 40 subjects diagnosed with PCOS. Subjects were randomly allocated into two groups to intake either 100 mg CoQ10 (n = 20) or placebo (n = 20) per day for 12 weeks. Gene expression related to insulin, lipid and inflammation were quantified in blood samples of PCOS women with RT-PCR method. RESULTS: Results of RT-PCR shown that compared with the placebo, CoQ10 intake downregulated gene expression of oxidized low-density lipoprotein receptor 1 (LDLR) (p < 0.001) and upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (p = 0.01) in peripheral blood mononuclear cells of subjects with PCOS. In addition, compared to the placebo group, CoQ10 supplementation downregulated gene expression of interleukin-1 (IL-1) (p = 0.03), interleukin-8 (IL-8) (p = 0.001) and tumor necrosis factor alpha (TNF-α) (p < 0.001) in peripheral blood mononuclear cells of subjects with PCOS. CONCLUSIONS: Overall, CoQ10 intake for 12 weeks in PCOS women significantly improved gene expression of LDLR, PPAR-γ, IL-1, IL-8 and TNF-α.

The effects of coenzyme Q10 supplementation on glucose metabolism and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Data on the effects of coenzyme Q10 (CoQ10) supplementation on metabolic profiles among subjects with polycystic ovary syndrome (PCOS) are scarce. OBJECTIVE: This study was carried out to evaluate the effects of CoQ10 supplementation on glucose metabolism and lipid profiles in subjects with PCOS. DESIGN, PATIENTS AND MEASUREMENTS: This randomized, double-blind, placebo-controlled trial was conducted on 60 women diagnosed with PCOS. Subjects were randomly assigned into two groups to intake either 100 mg CoQ10 supplements (N = 30) or placebo (N = 30) per day for 12 weeks. Markers of insulin metabolism and lipid profiles were assessed at first and 12 weeks after the intervention. RESULTS: After 12 weeks of intervention, compared to the placebo, subjects who received CoQ10 supplements had significantly decreased fasting plasma glucose (-0·24 ± 0·51 vs +0·01 ± 0·44 mmol/l, P = 0·04), serum insulin concentrations (-7·8 ± 14·4 vs +6·0 ± 15·0 pmol/l, P < 0·001), the homeostasis model of assessment-estimated insulin resistance (-0·3 ± 0·6 vs +0·2 ± 0·6, P = 0·001), the homeostasis model of assessment-estimated B-cell function (-5·4 ± 9·5 vs +4·5 ± 9·9, P < 0·001) and increased the quantitative insulin sensitivity check index (+0·006 ± 0·009 vs -0·006 ± 0·01, P < 0·001). In addition, changes in serum total- (-0·10 ± 0·48 vs +0·19 ± 0·50 mmol/l, P = 0·02) and LDL-cholesterol concentrations (-0·15 ± 0·40 vs +0·14 ± 0·49 mmol/l, P = 0·01) in supplemented women were significantly different from those of women in the placebo group. When we adjusted the analysis for baseline values of biochemical parameters, age and baseline BMI, serum LDL-cholesterol (P = 0·05) became nonsignificant, and other findings did not alter. CONCLUSIONS: Overall, CoQ10 supplementation for 12 weeks among subjects with PCOS had beneficial effects on glucose metabolism, serum total- and LDL-cholesterol levels.

The effects of dietary approaches to stop hypertension diet on weight loss, anti-Müllerian hormone and metabolic profiles in women with polycystic ovary syndrome: A randomized clinical trial.

OBJECTIVE: This study was designed to evaluate the effects of the dietary approaches to stop hypertension (DASH diet) on weight loss, anti-Müllerian hormone (AMH) and metabolic profiles in women with polycystic ovary syndrome (PCOS). DESIGN, PATIENTS AND MEASUREMENTS: A randomized controlled clinical trial was conducted among 60 overweight or obese patients with PCOS. Patients were randomly assigned to receive either low-calorie DASH (N=30) or control diet (N=30) for 12 weeks. The DASH and control diets were consisted of 52%-55% carbohydrates, 16%-18% proteins and 30% total fats; however, the DASH diet was designed to be rich in fruits, vegetables, whole grains, low-fat dairy products, cholesterol and refined grains. Both diets were equicaloric. RESULTS: Adherence to the DASH diet, compared to the control diet, resulted in a significant decrease in BMI (-1.6±0.5 vs -1.2±0.7 kg/m2 , P=.02). Significant decreases in AMH (-1.1±3.1 vs +0.3±0.7 ng/mL, P=.01), insulin (-25.2±51.0 vs -1.2±28.8 pmol/L, P=.02), homoeostasis model of assessment-estimated insulin resistance (-0.9±2.0 vs -0.1±1.0, P=.02), free androgen index (FAI; -0.03±0.09 vs +0.06±0.21, P=.02) and malondialdehyde (MDA) levels (-0.5±0.4 vs +0.2±0.3 µmol/L, P<.001), and significant increases in quantitative insulin sensitivity check index (+0.01±0.03 vs -0.004±0.01, P=.02), sex hormone-binding globulin (SHBG; +3.7±8.5 vs -1.5±7.2 nmol/L, P=.01) and nitric oxide (NO; +9.0±4.9 vs +0.6±2.3 µmol/L, P<.001) were also seen in the DASH group compared with the control group. CONCLUSIONS: Adherence to the DASH diet for 12 weeks among PCOS women had beneficial effects on BMI, AMH, insulin metabolism, SHBG, FAI, NO and MDA levels.

The Effects of Vitamin D Supplementation on Glucose Metabolism and Lipid Profiles in Patients with Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of vitamin D supplementation on glucose homeostasis parameters and lipid profiles in gestational diabetes (GDM) patients. We conducted an electronic systematic search of MEDLINE, and 4 other research databases from inception to August 2016, in addition to performing hand searches and consulting with experts in the field. The index of heterogeneity between studies was determined using Cochran (Q) and I-squared tests. Given the existing heterogeneity between studies, a fix or random effect model was performed to estimate the standardized mean difference (SMD) for each variable by using inverse variance method and Cohen statistics. Six randomized clinical trials (187 subjects and 184 controls) were included. The results showed that vitamin D supplementation significantly reduced the homeostasis model assessment of insulin resistance (HOMA-IR) [SMD -0.66; 95% confidence interval (CI), -1.14 to -0.18], homeostatic model assessment-B cell function (HOMA-B) (SMD -0.52; 95% CI, -0.79 to -0.25), LDL-cholesterol levels (SMD -0.33; 95% CI, -0.58 to -0.07), and significantly increased quantitative insulin sensitivity check index (QUICKI) (SMD 0.73; 95% CI, 0.26 to 1.20). We found no beneficial effect of vitamin D supplementation on fasting plasma glucose (FPG), insulin, HbA1c, total-, HDL-cholesterol, and triglycerides concentrations. In conclusion, this meta-analysis demonstrated that vitamin D supplementation may lead to an improvement in HOMA-IR, QUICKI, and LDL-cholesterol levels, but did not affect FPG, insulin, HbA1c, triglycerides, total- and HDL-cholesterol levels; however, vitamin D supplementation increased HOMA-B.

Effect of Two Different Doses of Vitamin D Supplementation on Metabolic Profiles of Insulin-Resistant Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

The current study was conducted to evaluate the effects of 2 different doses of vitamin D supplementation on metabolic profiles of insulin-resistant patients with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was performed on 90 insulin-resistant patients with PCOS according to the Rotterdam criteria aged 18-40 years old. Participants were randomly allocated into 3 groups to receive either 4 000 IU of vitamin D (n=30) or 1 000 IU of vitamin D (n=30) or placebo (n=30) per day for 12 weeks. Vitamin D supplementation (4 000 IU), compared with vitamin D (1 000 IU) and placebo, led to reduced fasting plasma glucose (-4.3±8.6 vs. -4.7±7.1 and +0.1±6.7 mg/dl, respectively, p=0.02), serum insulin concentrations (-2.7±2.7 vs. -1.4±4.2 and -0.1±4.1 µIU/ml, respectively, p=0.02), and HOMA-IR (-0.6±0.6 vs. -0.4±1.0 and -0.1±0.9, respectively, p=0.02). In addition, we found significant decreases in mean change of serum triglycerides (-10.3±7.3 vs. -3.6±14.5 and +6.9±23.8 mg/dl, respectively, p=0.001), VLDL- (-2.0±1.5 vs. -0.7±2.9 and +1.4±4.8 mg/dl, respectively, p=0.001), total- (-14.0±9.5 vs. -6.2±24.0 and +7.1±29.7 mg/dl, respectively, p=0.002), LDL- (-10.8±8.3 vs. -5.7±21.9 and +6.8±28.2 mg/dl, respectively, p=0.005), and total-/HDL-cholesterol ratio (-0.2±0.3 vs. -0.1±0.6 and +0.2±0.7 mg/dl, respectively, p=0.003) in the high-dose vitamin D group compared with low-dose vitamin D and placebo groups. Overall, vitamin D supplementation at a dosage of 4 000 IU/day for 12 weeks in insulin-resistant patients with PCOS had beneficial effects of glucose metabolism and lipid profiles compared with 1 000 IU/day of vitamin D and placebo groups.

Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Limited data are available assessing the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress of women with polycystic ovary syndrome (PCOS).This study was designed to determine the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress in women with PCOS. METHODS: In the current randomized, double-blind, placebo-controlled trial, 60 patients diagnosed with PCOS were randomized to take either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: After 12 weeks' intervention, compared with the placebo, carnitine supplementation resulted in a significant improvement in Beck Depression Inventory total score (-2.7 ± 2.3 versus -0.2 ± 0.7, p < 0.001), General Health Questionnaire scores (-6.9 ± 4.9 versus -0.9 ± 1.5, p < 0.001) and Depression Anxiety and Stress Scale scores (-8.7 ± 5.9 versus -1.2 ± 2.9, p = 0.001). In addition, changes in plasma total antioxidant capacity (TAC) (+84.1 ± 151.8 versus +4.6 ± 64.5 mmol/L, p = 0.01), malondialdehyde (MDA) (-0.4 ± 1.0 versus +0.5 ± 1.5 µmol/L, p = 0.01) and MDA/TAC ratio (-0.0005 ± 0.0010 versus +0.0006 ± 0.0019, p = 0.003) in the supplemented group were significantly different from the changes in these indicators in the placebo group. CONCLUSIONS: Overall, our study demonstrated that carnitine supplementation for 12 weeks among patients with PCOS had favorable effects on parameters of mental health and biomarkers of oxidative stress.

Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Limited data are available for evaluating the effects of oral carnitine supplementation on weight loss and metabolic profiles of women with polycystic ovary syndrome (PCOS). This study was designed to determine the effects of oral carnitine supplementation on weight loss, and glycaemic and lipid profiles in women with PCOS. DESIGN, PATIENTS AND MEASUREMENTS: In a prospective, randomized, double-blind, placebo-controlled trial, 60 overweight patients diagnosed with PCOS were randomized to receive either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at the beginning and the end of the study to quantify parameters of glucose homoeostasis and lipid concentrations. RESULTS: At the end of the 12 weeks, taking carnitine supplements resulted in a significant reduction in weight (-2·7 ± 1·5 vs +0·1 ± 1·8 kg, P < 0·001), BMI (-1·1 ± 0·6 vs +0·1 ± 0·7 kg/m(2) , P < 0·001), waist circumference (WC) (-2·0 ± 1·3 vs -0·3 ± 2·0 cm, P < 0·001) and hip circumference (HC) (-2·5 ± 1·5 vs -0·3 ± 1·8 cm, P < 0·001) compared with placebo. In addition, compared with placebo, carnitine administration in women with PCOS led to a significant reduction in fasting plasma glucose (-0·38 ± 0·36 vs +0·11 ± 0·97 mmol/l, P = 0·01), serum insulin levels (-14·39 ± 25·80 vs +3·01 ± 37·25 pmol/l, P = 0·04), homoeostasis model of assessment-insulin resistance (-0·61 ± 1·03 vs +0·11 ± 1·43, P = 0·04) and dehydroepiandrosterone sulphate (-3·64 ± 7·00 vs -0·59 ± 3·20 µmol/l, P = 0·03). CONCLUSIONS: Overall, 12 weeks of carnitine administration in PCOS women resulted in reductions in weight, BMI, WC and HC, and beneficial effects on glycaemic control; however, it did not affect lipid profiles or free testosterone.

Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women.

Unfavorable metabolic profiles and oxidative stress in pregnancy are associated with several complications. This study was conducted to determine the effects of vitamin D supplementation on serum concentrations of high-sensitivity C-reactive protein (hs-CRP), metabolic profiles, and biomarkers of oxidative stress in healthy pregnant women. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 pregnant women aged 18-40 y old at 25 wk of gestation. Participants were randomly assigned to receive either 400 IU/d cholecalciferol supplements (n = 24) or placebo (n = 24) for 9 wk. Fasting blood samples were taken at study baseline and after 9 wk of intervention to quantify serum concentrations of hs-CRP, lipid concentrations, insulin, and biomarkers of oxidative stress. After 9 wk of intervention, the increases in serum 25-hydroxyvitamin D and calcium concentrations were greater in the vitamin D group (+3.7 µg/L and +0.20 mg/dL, respectively) than in the placebo group (-1.2 µg/L and -0.12 mg/dL, respectively; P < 0.001 for both). Vitamin D supplementation resulted in a significant decrease in serum hs-CRP (vitamin D vs. placebo groups: -1.41 vs. +1.50 µg/mL; P-interaction = 0.01) and insulin concentrations (vitamin D vs. placebo groups: -1.0 vs. +2.6 µIU/mL; P-interaction = 0.04) and a significant increase in the Quantitative Insulin Sensitivity Check Index score (vitamin D vs. placebo groups: +0.02 vs. -0.02; P-interaction = 0.006), plasma total antioxidant capacity (vitamin D vs. placebo groups: +152 vs. -20 mmol/L; P-interaction = 0.002), and total glutathione concentrations (vitamin D vs. placebo groups: +205 vs. -32 µmol/L; P-interaction = 0.02) compared with placebo. Intake of vitamin D supplements led to a significant decrease in fasting plasma glucose (vitamin D vs. placebo groups: -0.65 vs. -0.12 mmol/L; P-interaction = 0.01), systolic blood pressure (vitamin D vs. placebo groups: -0.2 vs. +5.5 mm Hg; P-interaction = 0.01), and diastolic blood pressure (vitamin D vs. placebo groups: -0.4 vs. +3.1 mm Hg; P-interaction = 0.01) compared with placebo. In conclusion, vitamin D supplementation for 9 wk among pregnant women has beneficial effects on metabolic status.

Favourable effects of the Dietary Approaches to Stop Hypertension diet on glucose tolerance and lipid profiles in gestational diabetes: a randomised clinical trial.

Although gestational diabetes mellitus (GDM) is associated with an increased risk of maternal and neonatal morbidity, there is no consensus as to the optimal approach of nutritional management in these patients. The present study was designed to assess the effect of the Dietary Approaches to Stop Hypertension (DASH) eating plan on glucose tolerance and lipid profiles of pregnant women with GDM. The present randomised controlled clinical trial was performed among thirty-four women diagnosed with GDM at 24-28 weeks of gestation. Subjects were randomly assigned to consume either the control diet (n 17) or the DASH eating pattern (n 17) for 4 weeks. The control diet was designed to contain 45-55% carbohydrates, 15-20% protein and 25-30% total fat. The macronutrient composition of the DASH diet was similar to the control diet; however, the DASH diet was rich in fruits, vegetables, whole grains and low-fat dairy products, and contained lower amounts of saturated fats, cholesterol and refined grains with a total of 2400 mg Na/d. Fasting blood samples were taken at baseline and after 4 weeks of intervention to measure fasting plasma glucose, glycated Hb (HbA1c) and lipid profiles. Participants underwent a 3 h oral glucose tolerance tests and blood samples were collected at 60, 120 and 180 min to measure plasma glucose levels. Adherence to the DASH eating pattern, compared with the control diet, resulted in improved glucose tolerance such that plasma glucose levels reduced at 60 (21·86 v. 20·45 mmol/l, Pgroup = 0·02), 120 (22·3 v. 0·2 mmol/l, Pgroup = 0·001) and 180 min (21·7 v. 0·22 mmol/l, Pgroup = 0·002) after the glucose load. Decreased HbA1c levels (20·2 v. 0·05 %, Pgroup = 0·001) was also seen in the DASH group compared with the control group. Mean changes for serum total (20·42 v. 0·31 mmol/l, Pgroup = 0·01) and LDL-cholesterol (20·47 v. 0·22 mmol/l, Pgroup = 0·005), TAG (20·17 v. 0·34 mmol/l, Pgroup = 0·01) and total:HDL-cholesterol ratio (20·6 (SD 0·9) v. 0·3 (SD 0·8), Pgroup = 0·008) were significantly different between the two diets. Additionally, consumption of the DASH diet favourably influenced systolic blood pressure (22·6 v. 1·7 mmHg, Pgroup = 0·001). Mean changes of fasting plasma glucose (20·29 v. 0·15 mmol/l, Pgroup = 0·09) were nonsignificant comparing the DASH diet with the control diet. In conclusion, consumption of the DASH eating pattern for 4 weeks among pregnant women with GDM resulted in beneficial effects on glucose tolerance and lipid profiles compared with the control diet.

MicroRNA and gynecological cancers: Focus on miR-195.

Different cancer types have been shown to have down-regulated expression levels of miR-195 as an anti-tumor agent. MiR-195 family members can inhibit cancer cell proliferation, angiogenesis, epithelial-mesenchymal transition and metastases, immunosuppression, glycolysis, drug resistance, and cancer stem cell development by targeting the 3'-UTR of the mRNA of different pro-tumor genes. MiR-195 identified as a tumor suppressor miR in a variety of cancers, most notably gynecological malignancies such as cervical, endometrial, and ovarian carcinoma. As a result, restoring miR-195 expression should be regarded as a potential therapy for either prevention or treatment of gynecological cancers. This review will present the most recent data about miR-195-mediated anti-tumor effects in gynecological malignancies, emphasizing its downstream signaling pathways and target genes, as well as prospective treatment techniques.

Effects of Carnitine Administration on Carotid Intima-media Thickness and Inflammatory Factors in Patients with Polycystic Ovary Syndrome: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: This study was performed to evaluate the effects of carnitine administration on carotid intima-media thickness (CIMT) and inflammatory markers in women with polycystic ovary syndrome (PCOS). METHODS: This randomized, double-blind, placebo-controlled trial was conducted among 60 women diagnosed with PCOS according to the Rotterdam criteria, aged 18-40 years. Participants were randomly allocated into two groups to intake either 250 mg/day carnitine (n = 30) or placebo (n = 30) for 12 weeks. High-resolution carotid ultrasonography was conducted at baseline and after the 12-week intervention. RESULTS: After the 12-week intervention, compared with the placebo, carnitine supplementation resulted in a significant decrease in maximum levels of the left CIMT (-0.01 ± 0.02 vs. +0.002 mm ± 0.006 mm, P = 0.001), mean levels of the left CIMT (-0.01 ± 0.02 vs. +0.001 mm ± 0.01 mm, P = 0.001), maximum levels of the right CIMT (-0.01 ± 0.02 vs. +0.006 mm ± 0.01 mm, P < 0.001), and mean levels of the right CIMT (-0.01 ± 0.02 vs. +0.002 mm ± 0.01 mm, P = 0.001). Change in plasma nitric oxide (NO) (+2.4 ± 3.6 vs. +0.2 ± 2.3 µmol/L, P = 0.007) was significantly different between the supplemented patients and placebo group. We did not see any significant effect in serum high sensitivity C-reactive protein (hs-CRP) following the supplementation of carnitine compared with the placebo. CONCLUSIONS: Overall, carnitine administration for 12 weeks to participants with PCOS had beneficial effects on CIMT and plasma NO, but did not affect serum hs-CRP levels.

The Effects of Probiotic Supplementation on Genetic and Metabolic Profiles in Patients with Gestational Diabetes Mellitus: a Randomized, Double-Blind, Placebo-Controlled Trial.

This study was carried out to evaluate the effects of probiotic supplementation on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM) who were not on oral hypoglycemic agents. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 patients with GDM. Participants were randomly divided into two groups to intake either probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum (2 × 109 CFU/g each) (n = 24) or placebo (n = 24) for 6 weeks. Probiotic intake upregulated peroxisome proliferator-activated receptor gamma (P = 0.01), transforming growth factor beta (P = 0.002) and vascular endothelial growth factor (P = 0.006), and downregulated gene expression of tumor necrosis factor alpha (P = 0.03) in peripheral blood mononuclear cells of subjects with GDM. In addition, probiotic supplementation significantly decreased fasting plasma glucose (ß, - 3.43 mg/dL; 95% CI, - 6.48, - 0.38; P = 0.02), serum insulin levels (ß, - 2.29 µIU/mL; 95% CI, - 3.60, - 0.99; P = 0.001), and insulin resistance (ß, - 0.67; 95% CI, - 1.05, - 0.29; P = 0.001) and significantly increased insulin sensitivity (ß, 0.009; 95% CI, 0.004, 0.01; P = 0.001) compared with the placebo. Additionally, consuming probiotic significantly decreased triglycerides (P = 0.02), VLDL-cholesterol (P = 0.02), and total-/HDL-cholesterol ratio (P = 0.006) and significantly increased HDL-cholesterol levels (P = 0.03) compared with the placebo. Finally, probiotic administration led to a significant reduction in plasma malondialdehyde (P < 0.001), and a significant elevation in plasma nitric oxide (P = 0.01) and total antioxidant capacity (P = 0.01) was observed compared with the placebo. Overall, probiotic supplementation for 6 weeks to patients with GDM had beneficial effects on gene expression related to insulin and inflammation, glycemic control, few lipid profiles, inflammatory markers, and oxidative stress.