Metabolic responses, PPAR-γ and TNF-α gene expression in type2 diabetic rats subsequent vanadyl sulfate treatment.

Vanadyl sulfate (VS), is a component of some food supplements and experimental drugs. This study was carried out to present a novel method for induction of Type 2 diabetes in rats, then for the first time in literature, for evaluating the effect of VS on metabolic parameters and gene expression, simultaneously. 40 male wistar rats were distributed between the four groups, equally. High fat diet and fructose were used for diabetes induction. Diabetic rats treated by two different dose of VS for 12 weeks. Metabolic profiles were evaluated by commercial available kits and gene expression were assayed by real time-PCR. Compared to controls, in non-treated diabetic rats, weight, glucose, triglyceride, total cholesterol, insulin and insulin resistance were increased significantly (p-value <0.05) that indicated induction of type 2 diabetes. Further, the results showed that VS significantly reduced weight, insulin secretion, Tumor Necrosis Factor-alpha (TNF-α) genes expression, lipid profiles except HDL that we couldn't find any significant change and increased Peroxisome Proliferator-Activated Receptor- gamma (PPAR-γ) gene expression in VS-treated diabetic animals in comparison with the non-treated diabetics. Our study demonstrated that vanadyl supplementation in diabetic rats had advantageous effects on metabolic profiles and related gene expression.

The preventive effect of heat-killed Lactobacillus plantarum on male reproductive toxicity induced by cholestasis in rats.

This study investigated the preventive effect of heat-killed Lactobacillus plantarum (L. plantarum) on cholestasis-induced male reproductive toxicity in rats. Rats were divided into control normal, sham control, bile duct ligation (BDL) control, and BDL with heat-killed L. plantarum supplementation groups. The effects on sexual hormones, testicular and epididymal histology, sperm parameters, oxidative stress markers, and inflammatory gene expression were evaluated. Compared to the BDL control group, the BDL + heat-killed L. plantarum group showed higher levels of normal sperm, luteinizing hormone, testosterone, total antioxidant capacity, and catalase activity, indicating improved reproductive function. Conversely, markers of oxidative stress, such as total oxidative status, oxidative stress index, and carbonyl protein, were lower in the BDL + heat-killed L. plantarum group. The expression levels of inflammatory genes tumor necrosis factor-alpha and interleukin-6 were reduced, while interleukin-10 gene expression was increased in the BDL + heat-killed L. plantarum group. Histological evaluation confirmed the positive effects of heat-killed L. plantarum intervention on testicular parameters. In conclusion, heat-killed L. plantarum supplementation protects against cholestasis-induced male reproductive dysfunction in rats, as evidenced by improvements in hormonal balance, sperm quality, oxidative stress, and inflammation.

Circular RNAs: Emerging Modulators in the Pathophysiology of Polycystic Ovary Syndrome and their Clinical Implications.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine/metabolic disorder in women of reproductive age. PCOS is characterized by hyperandrogenism, polycystic ovary morphology, and ovulatory dysfunction/anovulation. It involves multiple effects in patients, including granulosa/theca cell hyperplasia, menstrual disturbances, infertility, acne, obesity, insulin resistance, and cardiovascular disorders. Biochemical analyses and the results of RNA sequencing studies in recent years have shown a type of non-coding RNAs as a splicing product known as circular RNAs (circRNAs). Several biological functions have been identified in relation to circRNAs, including a role in miRNA sponge, protein sequestration, increased parental gene expression, and translation leading to polypeptides. These circular molecules are more plentiful and specialized than other types of RNAs. For this reason, they are referred to as potential biomarkers in different diseases. Evidence suggests that circRNAs may have regulatory potentials through different signaling pathways, such as the miRNA network. Probably most experts in the field of obstetricians are not aware of circRNAs as a useful biomarker. Therefore, this review focused on the researches that have been done on the involvement of circRNAs in PCOS and summarized recent supportive evidence, and evaluated the circRNA association and mechanisms involved in PCOS.

Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.

Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment.

Gliomas are the most lethal primary brain tumors in adults. These highly invasive tumors have poor 5-year survival for patients. Gliomas are principally characterized by rapid diffusion as well as high levels of cellular heterogeneity. However, to date, the exact pathogenic mechanisms, contributing to gliomas remain ambiguous. MicroRNAs (miRNAs), as small noncoding RNAs of about 20 nucleotides in length, are known as chief modulators of different biological processes at both transcriptional and posttranscriptional levels. More recently, it has been revealed that these noncoding RNA molecules have essential roles in tumorigenesis and progression of multiple cancers, including gliomas. Interestingly, miRNAs are able to modulate diverse cancer-related processes such as cell proliferation and apoptosis, invasion and migration, differentiation and stemness, angiogenesis, and drug resistance; thus, impaired miRNAs may result in deterioration of gliomas. Additionally, miRNAs can be secreted into cerebrospinal fluid (CSF), as well as the bloodstream, and transported between normal and tumor cells freely or by exosomes, converting them into potential diagnostic and/or prognostic biomarkers for gliomas. They would also be great therapeutic agents, especially if they could cross the blood-brain barrier (BBB). Accordingly, in the current review, the contribution of miRNAs to glioma pathogenesis is first discussed, then their glioma-related diagnostic/prognostic and therapeutic potential is highlighted briefly.

The Protective Effects of Securigera securidaca Seed Extract on Liver Injury Induced by Bile Duct Ligation in Rats.

This study is aimed at evaluating the effects of Securigera securidaca (SS) seed extract on cholestatic liver injury induced by bile duct ligation (BDL) in rats. Total polyphenols and flavonoids in SS seed extract were determined using a colorimetric assay, and their components were quantified using HPLC. Rats in four groups underwent BDL at the common bile duct and were treated for 21 days with either oral distilled water as vehicle, vitamin C, 100 mg/kg SS seed extract, or 200 mg/kg SS seed extract. Rats in the fifth group underwent abdominal incision without BDL and were treated with distilled water, and rats in the sixth group were healthy and received nothing. Finally, rats were sacrificed, blood samples were analyzed through biochemical methods, liver tissues were histologically assessed, and the expression of the TGFß-1, iNOS, caspase-3, and α-SMA genes in the liver was assessed through real-time PCR. BDL significantly increased, and SS seed extract significantly decreased the serum levels of bilirubin and liver function enzymes. Moreover, SS seed extract suppressed the expression of the TGFß-1, iNOS, caspase-3, and α-SMA genes, reduced the levels of nitric oxide, malondialdehyde, and protein carbonyl, and increased the levels of glutathione, total antioxidant capacity, and SOD and catalase enzyme activity in the serum and liver. Extract at a dose of 100 mg/kg had significant positive effects on liver morphology and parenchyma structure in a dose-dependent manner.

Anti-inflammatory and antioxidative effects of thiamin supplements in patients with gestational diabetes mellitus.

OBJECTIVE: The aim of this study was to evaluate the effects of thiamin supplementation on biomarkers of inflammation and oxidative stress in patients with gestational diabetes mellitus (GDM). METHODS: This randomized, double-blind, placebo-controlled trial was conducted among 60 patients with GDM. Patients were randomly allocated into two groups to receive either 100 mg/day thiamin supplements (n = 30) or placebo (n = 30) for 6 weeks. RESULTS: Thiamin supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (ß - 0.98 mg/L; 95% CI, -1.54, -0.42; p = .001) and plasma malondialdehyde (MDA) levels (ß - 0.86 µmol/L; 95% CI, -1.15, -0.57; p < .001) when compared with the placebo. In addition, thiamin supplementation downregulated gene expression of tumor necrosis factor-alpha (TNF-α) (p = .002) in peripheral blood mononuclear cells of patients with GDM. Thiamin supplementation did not affect other biomarkers of inflammation and oxidative stress. CONCLUSION: Overall, thiamin supplementation for 6 weeks to patients with GDM significantly reduced hs-CRP and MDA levels, and gene expression of TNF-α, but did not affect other biomarkers of inflammation and oxidative stress. CLINICAL TRIAL REGISTRATION NUMBER: Clinical Trials.govIdentifier no. http://www.irct.ir: IRCT20170513033941N58.

Comparison Between Biomarkers of Kidney Injury, Inflammation, and Oxidative Stress in Patients with Diabetic Nephropathy and Type 2 Diabetes Mellitus.

INTRODUCTION: This study was conducted to compare parameters of kidney injury, oxidative stress and inflammation in people with diabetic nephropathy (DN) and type 2 diabetes mellitus (T2DM). METHODS: In a cross-sectional study, 57 cases with DN and 57 cases with T2DM were included in the study. Fasting blood samples were obtained to determine parameters of kidney injury, oxidative stress and inflammation. RESULTS: The current study showed that patients with DN had higher tumor necrosis factor-α (TNF-α) (167.0 ± 40.1 vs. 151.4 ± 37.4 ng/L, P < .05) and matrix metalloproteinase-2 (MMP-2) concentrations (1625.2 ± 631.0 vs. 1391.5 ± 465.4 ng/mL, P < .05) compared with T2DM cases. Moreover, we observed a non-significant increase in MMP-9 levels among patients with DN compared with individuals with T2DM (4864.4 ± 1934.3 vs. 4239.2 ± 1853.9 ng/L, P > .05). Furthermore, advanced glycation end products (AGEs) levels in patients with DN were higher than that of patients with T2DM (8511.7 ± 1799.9 vs. 7660.7 ± 1711.9 AU, P < .05), but the difference in malondialdehyde value was not significant. Finally, we found that total protein levels in cases with DN were enhanced compared with individuals with T2DM (7.1 ± 0.5 vs. 6.9 ± 0.6 mg/dL, P < .05); however, other markers of kidney injury did not change. CONCLUSIONS: In conclusion, the results of present study revealed that few markers of inflammation and oxidative stress including TNF-α, MMP-2, AGEs levels and total protein levels in patients with DN were significantly higher than that of patients with T2DN. Further studies are necessary to confirm these findings.

Effects of curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effect of curcumin on body weight, glycemic control and serum lipids in women suffering from polycystic ovary syndrome (PCOS). METHODS: The current randomized, double-blinded, placebo-controlled clinical trial was performed on 60 subjects with PCOS, aged 18-40 years old. Subjects were randomly allocated to take 500 mg/day curcumin (n = 30) or placebo (n = 30) for 12 weeks. Glycemic control and serum lipids were measured at baseline and after the 12-week intervention. Using RT-PCR method, gene expression related to insulin and lipid metabolism was evaluated. RESULTS: Curcumin significantly decreased weight (-0.8 ± 0.9 vs. -0.2 ± 0.8 kg, P = 0.03) and BMI (-0.3 ± 0.4 vs. -0.1 ± 0.3 kg/m2, P = 0.03). Curcumin, compared with the placebo, significantly reduced fasting glucose (ß -2.63 mg/dL; 95% CI, -4.21, -1.05; P = 0.002), serum insulin (ß -1.16 µIU/mL; 95% CI, -2.12, -0.19; P = 0.02), insulin resistance (ß -0.26; 95% CI, -0.48, -0.03; P = 0.02), and significantly increased insulin sensitivity (ß 0.006; 95% CI, 0.001, 0.01; P = 0.02). In addition, taking curcumin was associated with a significant reduction in total cholesterol (ß -15.86 mg/dL; 95% CI, -24.48, -7.24; P = 0.001), LDL-cholesterol (ß -16.09 mg/dL; 95% CI, -25.11, -7.06; P = 0.001) and total-/HDL-cholesterol ratio (ß -0.62; 95% CI, -0.93, -0.30; P < 0.001), and a significant increase in HDL-cholesterol levels (ß 2.14 mg/dL; 95% CI, 0.36, 3.92; P = 0.01) compared with the placebo. Additionally, curcumin administration up-regulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03) and low-density lipoprotein receptor (LDLR) (P < 0.001) compared with the placebo. CONCLUSIONS: Overall, curcumin administration for 12 weeks to women with PCOS had beneficial effects on body weight, glycemic control, serum lipids except triglycerides and VLDL-cholesterol levels, and gene expression of PPAR-γ and LDLR. Registered under Clinical Trials.gov Identifier no. http://www.irct.ir: IRCT20170513033941N50.

The effects of n-3 fatty acids from flaxseed oil on genetic and metabolic profiles in patients with gestational diabetes mellitus: a randomised, double-blind, placebo-controlled trial.

The present study was performed to evaluate the effects of n-3 fatty acids from flaxseed oil on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM). This randomised, double-blind, placebo-controlled clinical trial was performed in sixty women with GDM. Participants were randomly divided into two groups to intake either 2 × 1000 mg/d n-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid in each capsule (n 30) or placebo (n 30) for 6 weeks. n-3 Fatty acid intake up-regulated PPAR-γ (P < 0·001) and LDL receptor (P = 0·004) and down-regulated gene expression of IL-1 (P = 0·002) and TNF-α (P = 0·001) in peripheral blood mononuclear cells of subjects with GDM. In addition, n-3 fatty acid supplementation reduced fasting plasma glucose (P = 0·001), insulin levels (P = 0·001) and insulin resistance (P < 0·001) and increased insulin sensitivity (P = 0·005) when compared with the placebo. Additionally, n-3 fatty acid supplementation was associated with a decrease in TAG (P < 0·001), VLDL-cholesterol (P < 0·001), total cholesterol (P = 0·01) and total cholesterol:HDL-cholesterol ratio (P = 0·01) when compared with placebo. n-3 Fatty acid administration was also associated with a significant reduction in high-sensitivity C-reactive protein (P = 0·006) and malondialdehyde (P < 0·001), and an increase in total nitrite (P < 0·001) and total glutathione levels (P = 0·006) when compared with the placebo. n-3 Fatty acid supplementation for 6 weeks to women with GDM had beneficial effects on gene expression related to insulin, lipid and inflammation, glycaemic control, lipids, inflammatory markers and oxidative stress.

The Effects of Selenium Supplementation on Clinical Symptoms and Gene Expression Related to Inflammation and Vascular Endothelial Growth Factor in Infertile Women Candidate for In Vitro Fertilization.

This study was performed to determine the effects of selenium supplementation on clinical symptoms and gene expression related to inflammatory markers in infertile women with polycystic ovary syndrome (PCOS) who were candidate for in vitro fertilization (IVF). Thirty-six women candidate for IVF were recruited in this randomized double-blinded, placebo-controlled trial. They (n = 18/group) were randomly assigned into intervention groups to take either 200 µg/day of selenium or placebo for 8 weeks. RT-PCR findings indicated that selenium supplementation downregulated gene expression of interleukin-1 (IL-1) (P < 0.004) and tumor necrosis factor alpha (TNF-α) (P = 0.02) in lymphocytes of patients with PCOS compared with the placebo. In addition, selenium supplementation upregulated gene expression of vascular endothelial growth factor (VEGF) (P = 0.001) in lymphocytes of patients with PCOS compared with the placebo. Selenium supplementation had no significant effect on clinical symptoms and gene expression of IL-8 (P = 0.10) and transforming growth factor beta (TGF-ß) (P = 0.63). Overall, our findings documented that selenium supplementation for 8 weeks to infertile women candidate for IVF improved IL-1, TNF-α, and VEGF gene expression, though selenium had no effect on clinical symptoms and, IL-8 and TGF-ß gene expression. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N23.

Effects of Chromium and Carnitine Co-supplementation on Body Weight and Metabolic Profiles in Overweight and Obese Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.

The primary aim of our study was to determine the influence of taking chromium plus carnitine on insulin resistance, with a secondary objective of evaluating the influences on lipid profiles and weight loss in overweight subjects with polycystic ovary syndrome (PCOS). In a 12-week randomized, double-blind, placebo-controlled clinical trial, 54 overweight women were randomly assigned to receive either supplements (200 µg/day chromium picolinate plus 1000 mg/day carnitine) or placebo (27/each group). Chromium and carnitine co-supplementation decreased weight (- 3.6 ± 1.8 vs. - 1.0 ± 0.7 kg, P < 0.001), BMI (- 1.3 ± 0.7 vs. - 0.3 ± 0.3 kg/m2, P < 0.001), fasting plasma glucose (FPG) (- 5.1 ± 6.0 vs. - 1.1 ± 4.9 mg/dL, P = 0.01), insulin (- 2.0 ± 1.4 vs. - 0.2 ± 1.2 µIU/mL, P < 0.001), insulin resistance (- 0.5 ± 0.4 vs. - 0.04 ± 0.3, P < 0.001), triglycerides (- 18.0 ± 25.2 vs. + 5.5 ± 14.4 mg/dL, P < 0.001), total (- 17.0 ± 20.3 vs. + 3.6 ± 12.0 mg/dL, P < 0.001), and LDL cholesterol (- 13.3 ± 19.2 vs. + 1.4 ± 13.3 mg/dL, P = 0.002), and elevated insulin sensitivity (+ 0.007 ± 0.005 vs. + 0.002 ± 0.005, P < 0.001). In addition, co-supplementation upregulated peroxisome proliferator-activated receptor gamma (P = 0.02) and low-density lipoprotein receptor expression (P = 0.02). Overall, chromium and carnitine co-supplementation for 12 weeks to overweight women with PCOS had beneficial effects on body weight, glycemic control, lipid profiles except HDL cholesterol levels, and gene expression of PPAR-γ and LDLR. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N38.

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome.

Purpose: The aim of the current study was to evaluate the effect of melatonin administration on clinical, hormonal, inflammatory, and genetic parameters in women with polycystic ovarian syndrome (PCOS). Methods: The present randomized, double-blinded, placebo-controlled clinical trial was conducted among 56 patients with PCOS, aged 18-40 years old. Subjects were randomly allocated to take either 5 mg melatonin supplements (n = 28) or placebo (n = 28) twice a day for 12 weeks. Results: Melatonin administration significantly reduced hirsutism (ß -0.47; 95% CI, -0.86, -0.09; P = 0.01), serum total testosterone (ß -0.11 ng/mL; 95% CI, -0.21, -0.02; P = 0.01), high-sensitivity C-reactive protein (hs-CRP) (ß -0.61 mg/L; 95% CI, -0.95, -0.26; P = 0.001), and plasma malondialdehyde (MDA) levels (ß -0.25 µmol/L; 95% CI, -0.38, -0.11; P < 0.001), and significantly increased plasma total antioxidant capacity (TAC) levels (ß 106.07 mmol/L; 95% CI, 62.87, 149.28; P < 0.001) and total glutathione (GSH) (ß 81.05 µmol/L; 95% CI, 36.08, 126.03; P = 0.001) compared with the placebo. Moreover, melatonin supplementation downregulated gene expression of interleukin-1 (IL-1) (P = 0.03) and tumor necrosis factor alpha (TNF-α) (P = 0.01) compared with the placebo. Conclusions: Overall, melatonin administration for 12 weeks to women with PCOS significantly reduced hirsutism, total testosterone, hs-CRP, and MDA, while increasing TAC and GSH levels. In addition, melatonin administration reduced gene expression of IL-1 and TNF-α. Clinical Trial Registration: www.irct.ir, identifier IRCT2017082733941N9, Available online at: https://www.irct.ir/trial/26051.

Carnitine and chromium co-supplementation affects mental health, hormonal, inflammatory, genetic, and oxidative stress parameters in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to evaluate the effect of the co-administration of carnitine and chromium on mental health, hormonal, inflammatory and genetic parameters in women with PCOS. METHODS: This randomized, double-blinded, placebo-controlled clinical trial was conducted on 54 subjects, aged 18-40 years old. Subjects were randomly allocated to take either 1000 mg/d carnitine plus 200 µg/d chromium as chromium picolinate (n = 26) or placebo (n = 27) for 12 weeks. RESULTS: Carnitine and chromium co-supplementation, compared with the placebo, significantly improved beck depression inventory (ß - 0.84; 95% CI, -1.51, -0.17; p = 0.01), general health questionnaire scores (ß - 1.13; 95% CI, -2.13, -0.14; p = 0.02) and depression anxiety and stress scale scores (ß - 0.96; 95% CI, -0.78, -0.14; p = 0.02). Participants who received carnitine plus chromium supplements had significantly lower total testosterone (ß - 0.15 ng/mL; 95% CI, -0.24, -0.06; p = 0.002), hirsutism (ß - 0.48; 95% CI, -0.91, -0.06; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (ß - 1.02 mg/L; 95% CI, -1.79, -0.25; p = 0.01), and malondialdehyde (MDA) levels (ß - 0.38 µmol/L; 95% CI, -0.56, -0.20; p < 0.001), and higher total antioxidant capacity (TAC) levels (ß 107.18 mmol/L; 95% CI, 44.24, 170.12; p = 0.001) compared with the placebo. Moreover, carnitine and chromium co-supplementation upregulated gene expression of interleukin-6 (IL-6) (p = 0.02) and tumor necrosis factor alpha (TNF-α) (p = 0.02) compared with the placebo. CONCLUSION: Overall, the co-administration of carnitine and chromium for 12 weeks to women with PCOS had beneficial effects on mental health parameters, serum total testosterone, mF-G scores, hs-CRP, TAC and MDA levels, and gene expression of IL-6 and TNF-α.

Effects of melatonin administration on mental health parameters, metabolic and genetic profiles in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effect of melatonin supplementation on mental health parameters, metabolic and genetic parameters in women suffering from polycystic ovary syndrome (PCOS). METHODS: This randomized, double-blinded, placebo-controlled clinical trial was performed on 58 subjects, aged 18-40 years old. Subjects were randomly allocated to take either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 29) or placebo (n = 29) once a day 1 h before bedtime for 12 weeks. Glycemic control and lipid profiles were measured at baseline and after the 12-week intervention. Using RT-PCR method, gene expression related to insulin and lipid metabolism was conducted on peripheral blood mononuclear cells (PBMCs) of PCOS women. RESULTS: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (ß -2.15; 95% CI, -3.62, -0.68; P = 0.005), Beck Depression Inventory index (ß -3.62; 95% CI, -5.53, -1.78; P<0.001) and Beck Anxiety Inventory index (ß -1.95; 95% CI, -3.41, -0.48; P = 0.01) compared with the placebo. In addition, melatonin administration, compared with the placebo, significantly reduced serum insulin (ß -1.20 µIU/mL; 95% CI, -2.14, -0.26; P = 0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (ß -0.28; 95% CI, -0.50, -0.05; P = 0.01), serum total- (ß -7.96 mg/dL; 95% CI, -13.75, -2.17; P = 0.008) and LDL-cholesterol levels (ß -5.88 mg/dL; 95% CI, -11.42, -0.33; P = 0.03), and significantly increased the quantitative insulin sensitivity check index (QUICKI) (ß 0.008; 95% CI, 0.002, 0.014; P = 0.007). Moreover, melatonin supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.004) and low-density lipoprotein receptor (LDLR) (P = 0.01) compared with the placebo. CONCLUSIONS: Overall, melatonin administration for 12 weeks had beneficial effects on mental health parameters, insulin levels, HOMA-IR, QUICKI, total- and LDL-cholesterol levels, and gene expression of PPAR-γ and LDLR among women with PCOS.

Comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome: a randomized controlled clinical trial.

This investigation was conducted to evaluate comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome (PCOS). This randomized controlled trial was conducted on 53 women with PCOS, aged 18-40 years old. Subjects were randomly allocated into two groups to take either myo-inositol (n = 26) or metformin (n = 27) for 12 weeks. Myo-inositol supplementation, compared with metformin, significantly reduced fasting plasma glucose (FPG) (ß -5.12 mg/dL; 95% CI, -8.09, -2.16; p=.001), serum insulin levels (ß -1.49 µIU/mL; 95% CI, -2.28, -0.70; p<.001), homeostasis model of assessment-insulin resistance (ß -0.36; 95% CI, -0.55, -0.17; p<.001), serum triglycerides (ß 12.42 mg/dL; 95% CI, -20.47, -4.37; p=.003) and VLDL-cholesterol levels (ß -2.48 mg/dL; 95% CI, -4.09, -0.87; p=.003), and significantly increased the quantitative insulin sensitivity check index (ß 0.006; 95% CI, 0.002, 0.01; p=.006) compared with metformin. Moreover, myo-inositol supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (p=.002) compared with metformin. Overall, taking myo-inositol, compared with metformin, for 12 weeks by women with PCOS had beneficial effects on glycemic control, triglycerides and VLDL-cholesterol levels, and gene expression of PPAR-γ.

The effects of vitamin E supplementation on endometrial thickness, and gene expression of vascular endothelial growth factor and inflammatory cytokines among women with implantation failure.

OBJECTIVE: Data on the effects of vitamin E supplementation on endometrial thickness, and gene expression of vascular endothelial growth factor (VEGF) and inflammatory cytokines among women with implantation failure are limited. This research was performed to determine the effects of vitamin E supplementation on endometrial thickness, and gene expression of VEGF and inflammatory cytokines among women with implantation failure. METHODS: A randomized clinical trial was done among 40 women with implantation failure aged 18-37 years old. Participants were randomly divided into two groups: group A (n = 20) received 400-IU vitamin E supplements and group B (n = 20) received placebo for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week treatment to determine biomarkers of oxidative stress, and gene expression of VEGF and inflammatory cytokines. RESULTS: After the 12-week intervention, compared with the placebo, women with implantation failure who consumed vitamin E supplements had significantly increased serum vitamin E levels (+18.6 ± 15.0 versus -1.5 ± 1.0 nmol/mL, p < .001) and endometrial thickness (+1.1 ± 0.9 versus -0.5 ± 0.3 mm, p = .01), and significantly decreased plasma malondialdehyde (MDA) concentrations (-0.4 ± 0.3 versus +0.4 ± 0.3 µmol/L, p < .004). In addition, results of RT-PCR demonstrated that compared with the placebo, vitamin E intake downregulated gene expression of low-density lipoprotein receptor (LDLR) (p = .008), interleukin-1 (IL-1) (p = .02), and tumor necrosis factor alpha (TNF-α) (p = .007) in peripheral blood mononuclear cells of women with implantation failure. CONCLUSIONS: Overall, vitamin E supplementation for 12 weeks among women with implantation failure had beneficial effects on endometrial thickness, MDA values, and gene expression of LDLR, IL-1, and TNF-α.

The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment.

This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (ß -4.08; 95 percent CI, -5.51, -2.65; P < 0.001), Beck Depression Inventory index (ß -5.46; 95% CI, -8.92, -2.00; P = 0.003) and Beck Anxiety Inventory index (ß -3.87; 95% CI, -5.96, -1.77; P = 0.001) and significantly increased International Index of Erectile Functions (ß 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (ß -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment-insulin resistance (ß -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher quantitative insulin sensitivity check index (ß 0.01; 95% CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (ß 3.71; 95% CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (ß -0.15; 95% CI, -0.27, -0.02; P = 0.02), malondialdehyde (ß -0.31; 95% CI, -0.57, -0.05; P = 0.02) and protein carbonyl (ß -0.06; 95% CI, -0.09, -0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles.