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.

The Effect of Heat-Killed Lactobacillus plantarum on Oxidative Stress and Liver Damage in Rats with Bile Duct Ligation-Induced Hepatic Fibrosis.

This study is aimed at evaluating the effects of heat-killed Lactobacillus plantarum (L. plantarum) on cholestatic liver injury induced by bile duct ligation (BDL) in rats. Rats in the first group were healthy (normal control) and in the second group underwent abdominal incision (sham control). Rats in the third and fourth groups underwent common bile duct ligation and were treated with either oral distilled water (BDL control group) or heat-killed L. plantarum (BDL + L. plantarum) for 28 days. Finally, rats were sacrificed, blood samples were analyzed through biochemical methods, liver and ileum tissue tissues were histologically assessed, and the expression of the αSMA, TNF-α, IL-6, and IL-10 genes in the liver and ZO-1 gene in ileum tissues were assessed through real-time PCR. The levels of bilirubin, liver function enzymes, NO, MDA, and carbonyl protein in the BDL + L. plantarum group were significantly lower than in the BDL control group (P ≤ 0.05). SOD and CAT activity in BDL + L. plantarum group was significantly greater than the BDL control group 1.4 and 3.0 times, respectively (P ≤ 0.001). Moreover, in the BDL + L. plantarum group, the expression of the α-SMA, TNF-α, and IL-6 genes was significantly lower (3.1, 2.9, and 2.5 times), and IL-10 and ZO-1 genes were significantly greater than the BDL control group by 2.1 and 3.6 times, respectively (P ≤ 0.05). The histological assessment also confirmed the greater effectiveness of heat-killed L. plantarum in improving the morphology and parenchymal structure of the liver. Taken together, our results suggest that heat-killed L. plantarum strains are potential therapeutic agents for hepatic fibrosis.

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.

Circular RNAs; powerful microRNA sponges to overcome diabetic nephropathy.

Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a drastic renal complication of type 1 and type 2 diabetes mellitus (DM). Poorly controlled DM over the years, may disrupt kidneys' blood vessels, leading to the hypertension (HTN) and DN onset. During DN, kidneys' waste filtering ability becomes disturbed. Being on a healthy lifestyle and controlling both DM and HTN are now the best proceedings to prevent or at least delay DN occurrence. Unfortunately, about one-fourth of diabetic individuals eventually experience the corresponding renal failure, and thus it is critical to discover effective diagnostic biomarkers and therapeutic strategies to combat DN. In the past few years, circular RNAs (circRNAs), as covalently closed endogenous non-coding RNAs (ncRNAs), are believed to affect DN pathogenesis in a positive manner. CircRNAs are able to impact different cellular processes and signaling pathways by targeting biological molecules or various molecular mechanisms. Still, as a key regulatory axis, circRNAs can select miRNAs as their molecular targets, in which they are considered as miRNA sponges. In this way, circRNA-induced suppression of particular miRNAs may prevent from DN progression or promotes the DN elimination. Since the expression of circRNAs has also been reported to be increased in DN-associated cells and tissues, they can be employed as either diagnostic biomarkers or therapeutic targets.

Metabolic and Anti-inflammatory Response to Melatonin Administration in Patients with Diabetic Nephropathy.

INTRODUCTION: Data on the effects of melatonin administration on metabolic parameters in patients with diabetic nephropathy (DN) is limited and controversial. This study was performed to analyze the effects of melatonin administration on metabolic status in patients with DN. METHODS: This randomized, double blind, placebo-controlled clinical trial was performed on 60 patients with DN. Patients were randomly assigned into two groups to take either 10 mg/d of melatonin (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were taken at baseline and 12 weeks after intervention to quantify metabolic parameters. RESULTS: Melatonin administration significantly reduced plasma fasting glucose (ß = -10.64 mg/dL; 95% CI: -20.37 to -0.90; P < .05), insulin (ß = -2.37 µIU/mL, 95% CI: -3.33 to -1.41; P < .001), insulin resistance (ß = -0.67, 95% CI: -0.98 to -0.35; P < .001), significantly increased insulin sensitivity (ß = 0.01, 95% CI: 0.006 to 0.01; P < .05), and plasma HDL-cholesterol levels (ß = 2.75 mg/dL, 95% CI: 0.75 to 4.75; P < .05) when compared with the placebo. Melatonin also caused a significant increase in total antioxidant capacity (TAC) (ß = 140.45 mmol/L; 95% CI: 80.48 to 200.41; P < .001), and glutathione (GSH) levels (ß = 50.36 µmol/L, 95% CI: 94.08 to 0.02; P < .05) when compared with placebo. Ultimately, melatonin could upregulate gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < .05) in comparison with placebo. CONCLUSION: Results of this study indicated that melatonin administration for 12 weeks in DN patients had beneficial effects on glycemic control, HDL-cholesterol, TAC and GSH levels, and gene expression of PPAR-γ, but did not affect other metabolic parameters.

Curcumin administration and the effects on psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes and coronary heart disease.

INTRODUCTION: This study assessed the effects of curcumin intake on psychological status, markers of inflammation and oxidative damage in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). METHOD: This randomized, double-blind, placebo-controlled trial was performed in 60 patients with T2DM and CHD, aged 45-85 years with 2- and 3-vessel CHD. Patients were randomized into two groups to receive either 1000 mg/day curcumin (n = 30) or placebo (n = 30) for 12 weeks. Using RT-PCR method, gene expression related to insulin metabolism and inflammatory markers on mononuclear cells from peripheral blood was evaluated. RESULT: Curcumin intake significantly decreased Pittsburgh Sleep Quality Index (PSQI) (ß -1.27; 95% CI, -2.27, -0.31; P = 0.01) compared to the placebo group. Curcumin intake caused a significant reduction in malondialdehyde (MDA) (ß -0.20 µmol/L; 95% CI, -0.36, -0.04; P = 0.01), significant increase in total antioxidant capacity (TAC) (ß 75.82 mmol/L; 95% CI, 3.400, 148.25; P = 0.04) and glutathione (GSH) levels (ß 63.48 µmol/L; 95% CI, 26.58, 100.37; P = 0.001) when compared with the placebo. Additionally, curcumin intake upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.01). CONCLUSION: Curcumin intake for 12 weeks in patients with T2DM and CHD had beneficial effects on PSQI, TAC, GSH, MDA values, and gene expression of PPAR-γ. This study was retrospectively registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT20170513033941N63).

The Effects of Nano-curcumin on Metabolic Status in Patients With Diabetes on Hemodialysis, a Randomized, Double Blind, Placebo-controlled Trial.

INTRODUCTION: This study evaluated the effects of nano-curcumin intake on metabolic status in patients with diabetes on hemodialysis (HD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed on 60 patients with diabetes on HD. Participants were randomly divided into two groups to take either 80 mg/d nano-curcumin (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: Nano-curcumin significantly decreased fasting plasma glucose (ß = -19.68 mg/dL, 95% CI: -33.48 to -5.88; P < .05) and serum insulin levels (ß = -1.70 µIU/mL, 95% CI: -2.96 to -0.44; P < .05) when compared with patients who received placebo. Nanocurcumin treatment was associated with a significant reduction in triglycerides (ß = -16.13 mg/dL, 95% CI: -31.51 to -0.75; P < .05), VLDL-cholesterol (ß = -3.22 mg/dL, 95% CI: -6.30 to -0.15; P < .05), total cholesterol (ß = -17.83 mg/dL, 95% CI: -29.22 to -6.45; P < .05), LDL-cholesterol (ß = -15.20 mg/dL, 95% CI: -25.53 to -4.87; P < .05), and total-cholesterol/HDL-cholesterol ratio (ß = -1.15, 95% CI: -0.2.10 to -0.21; P < .05) when compared with the placebo. Nanocurcumin also resulted in a significant reduction of serum high sensitivity CRP (ß = -0.78 mg/L, 95% CI: -1.41 to -0.15; P < .05), and plasma malondialdehyde (ß = -0.25 µmol/L, 95% CI: -0.45 to -0.04; P < .05); but also with a significant increase in plasma total antioxidant capacity (ß = 52.43 mmol/L; 95% CI: 4.52 to 100.35; P < .05) and total nitrite levels (ß = 3.62 µmol/L, 95% CI: 2.17 to 5.08; P < .001) when compared with placebo. CONCLUSION: Nano-curcumin intake for 12 weeks had beneficial effects on metabolic profile in patients with diabetes on HD.

Melatonin supplementation and the effects on clinical and metabolic status in Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was performed to evaluate the impact of melatonin supplementation on clinical and metabolic profiles in people with Parkinson's disease (PD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted among 60 patients with PD. Participants were randomly divided into two groups to intake either 10 mg melatonin (two melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day, 1 h before bedtime for 12 weeks. RESULTS: Melatonin supplementation significantly reduced the Unified Parkinson's Disease Rating Scale (UPDRS) part I score (ß -2.33; 95% CI, -3.57, -1.09; P < 0.001), Pittsburgh Sleep Quality Index (PSQI) (ß -1.82; 95% CI, -3.36, -0.27; P = 0.02), Beck Depression Inventory (BDI) (ß -3.32; 95% CI, -5.23, -1.41; P = 0.001) and Beck Anxiety Inventory (BAI) (ß -2.22; 95% CI, -3.84, -0.60; P = 0.008) compared with the placebo treatment. Compared with the placebo, melatonin supplementation resulted in a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (ß -0.94 mg/L; 95% CI, -1.55, -0.32; P = 0.003) and a significant elevation in plasma total antioxidant capacity (TAC) (ß 108.09 mmol/L; 95% CI, 78.21, 137.97; P < 0.001) and total glutathione (GSH) levels (ß 77.08 µmol/L; 95% CI, 44.29, 109.86; P < 0.001). Additionally, consuming melatonin significantly decreased serum insulin levels (ß -1.79 µIU/mL; 95% CI, -3.12, -0.46; P = 0.009), homeostasis model of assessment-insulin resistance (HOMA-IR) (ß -0.47; 95% CI, -0.80, -0.13; P = 0.007), total- (ß -13.16 mg/dL; 95% CI, -25.14, -1.17; P = 0.03) and LDL- (ß -10.44 mg/dL; 95% CI, -20.55, -0.34; P = 0.04) compared with the placebo. CONCLUSIONS: Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol, and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles.

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 Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study evaluated the effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis (HD) patients. DESIGN: A randomized, double-blind, placebo-controlled clinical trial was conducted in 60 diabetic HD patients, 18-80 years of age. Participants were randomly divided into 2 groups to take either melatonin (2 x 5mg/day) (n = 30) or placebo (n = 30) 1 hour before bedtime for 12 weeks. The effects of melatonin on mental health, metabolic status, and gene expression related to metabolic status were assessed using multiple linear regression adjusting for age and BMI. RESULTS: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (P = .007), Beck Depression Inventory index (P = .001), and Beck Anxiety Inventory index (P = .01) compared with the placebo. Additionally, melatonin administration significantly reduced fasting plasma glucose (ß = -21.77 mg/dL, 95% CI -33.22 to -10.33, P < .001), serum insulin levels (ß = -1.89 µIU/mL, 95% CI -3.34 to -0.45, P = .01), and homeostasis model of assessment-insulin resistance (ß = -1.45, 95% CI -2.10 to -0.80, P < .001), and significantly increased the quantitative insulin sensitivity check index (ß = 0.01, 95% CI 0.007-0.02, P < .001) compared with placebo treated subjects. In addition, melatonin administration resulted in a significant reduction in serum high sensitivity C-reactive protein (ß = -1.92 mg/L, 95% CI -3.02 to -0.83, P = .001) and plasma malondialdehyde (ß = -0.21 µmol/L, 95% CI -0.36 to -0.06, P = .005); also, significant rises in plasma total antioxidant capacity (ß = 253.87 mmol/L, 95% CI 189.18-318.56, P < .001) and nitric oxide levels (ß = 2.99 µmol/L, 95% CI 0.71-5.28, P = .01) were observed compared with the placebo. CONCLUSION: Overall, melatonin supplementation for 12 weeks to diabetic HD patients had beneficial effects on mental health, glycemic control, inflammatory markers, and oxidative stress.