Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial

We are not aware of any study examining the effects of long term vitamin D administration on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This study was performed to evaluate the effects of long-term vitamin D administration on regression and metabolic status of patients with CIN1. This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1. CIN1 diagnosis was performed based on specific diagnostic procedures of biopsy, pathological diagnosis, and colposcopy. Patients were randomly allocated into two groups to take 50,000 IU vitamin D3 supplements (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Fasting blood samples were taken at the beginning of the study and end-of-trial to measure related markers. After 6 months of vitamin D administration, greater percentage of women in the vitamin D group had regressed CIN1 (84.6 vs. 53.8%, P = 0.01) than those in the placebo group. Long-term vitamin D supplementation increased serum-25(OH) vitamin D levels in the intervention group compared to the placebo group (+12.3 ± 11.4 vs. -0.1 ± 3.7 ng/mL, P < 0.001). In addition, vitamin D intake led to significant decreases in serum insulin levels (−5.3 ± 7.3 vs. +2.4 ± 5.9 μIU/mL, P < 0.001), homeostasis model of assessment-insulin resistance (−1.2 ± 1.6 vs. +0.5 ± 1.2, P < 0.001), homeostatic model assessment-Beta cell function (P = 0.005) and a significant elevation in quantitative insulin sensitivity check index (+0.03 ± 0.04 vs. -0.007 ± 0.02, P < 0.001) compared with the placebo group. Additionally, significant increases in plasma nitric oxide (NO) (+15.5 ± 10.3 vs. +4.0 ± 13.4 μmol/L, P = 0.001), total antioxidant capacity (TAC) (P = 0.04), total glutathione (GSH) (+11.8 ± 153.5 vs. -294.2 ± 595.1 μmol/L, P = 0.01) and a significant reduction in plasma malondialdehyde (MDA) levels (−0.8 ± 1.0 vs. -0.03 ± 1.4 μmol/L, P = 0.03) were observed following the administration of vitamin D supplements compared with the placebo group. In conclusion, vitamin D3 administration for 6 months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism, plasma NO, TAC, GSH and MDA levels. Clinical trial registration numberwww.irct.ir: IRCT201412065623N30

ZIF-8 Modified Polypropylene Membrane: A Biomimetic Cell Culture Platform with a View to the Improvement of Guided Bone Regeneration.

PurposeDespite the significant advances in modeling of biomechanical aspects of cell microenvironment, it remains a major challenge to precisely mimic the physiological condition of the particular cell niche. Here, the metal-organic frameworks (MOFs) have been introduced as a feasible platform for multifactorial control of cell-substrate interaction, given the wide range of physical and mechanical properties of MOF materials and their structural flexibility.ResultsIn situ crystallization of zeolitic imidazolate framework-8 (ZIF-8) on the polydopamine (PDA)-modified membrane significantly raised surface energy, wettability, roughness, and stiffness of the substrate. This modulation led to an almost twofold increment in the primary attachment of dental pulp stem cells (DPSCs) compare to conventional plastic culture dishes. The findings indicate that polypropylene (PP) membrane modified by PDA/ZIF-8 coating effectively supports the growth and proliferation of DPSCs at a substantial rate. Further analysis also displayed the exaggerated multilineage differentiation of DPSCs with amplified level of autocrine cell fate determination signals, like BSP1, BMP2, PPARG, FABP4, ACAN, and COL2A. Notably, osteogenic markers were dramatically overexpressed (more than 100-folds rather than tissue culture plate) in response to biomechanical characteristics of the ZIF-8 layer.ConclusionHence, surface modification of cell culture platforms with MOF nanostructures proposed as a powerful nanomedical approach for selectively guiding stem cells for tissue regeneration. In particular, PP/PDA/ZIF-8 membrane presented ideal characteristics for using as a barrier membrane for guided bone regeneration (GBR) in periodontal tissue engineering

The effect of cumin cyminum l. Plus lime administration onweight loss and metabolic status in overweight subjects: A randomized double-blind placebo-controlled clinical trial

Background: Limited data are available regarding the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight subjects. Objectives: The current study aimed to assess the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight. Patients and Methods: This randomized double-blind placebo-controlled clinical trial was conducted on 72 subjects with overweight, aged 18 - 50 years old. Participants were randomly divided into three groups: Group A received high-dose Cumin cyminum L. and lime capsules (75 mg each, n = 24), group B low-dose Cumin cyminum L. and lime capsules (25 mg each, n = 24) and group C placebos (n = 24) twice daily for eight weeks. Results: After eightweeksof intervention, comparedwithlow-dose C.cyminumL. plus limeandplacebo, taking high-dose C.cyminum L. plus lime resulted in significant weight loss (in the high-dose group: -2.1±1.7 vs. in the low-dose group: -1.2±1.5 and in the placebo group: + 0.2 ± 1.3 kg, respectively; P < 0.001) and body mass index (-0.8 ± 0.6 vs. -0.5 ± 0.5 and +0.1 ± 0.5 kg/m2, respectively; P < 0.001). In addition, administration of high-dose C. cyminum L. plus limecomparedwith low-dose C. cyminum L. plus limeandplacebo, led to a significant reduction in fasting plasma glucose (FPG) (P < 0.001) and a significant rise in quantitative insulin sensitivity check index (QUICKI) (+ 0.02 ± 0.02 vs. + 0.01 ± 0.02 and 0.01 ± 0.01, respectively; P = 0.01). Moreover, a significant decrease in serum triglycerides (-14.1 ± 56.2 vs. +13.9 ± 36.8 and + 10.6 ± 25.1 mg/dL; respectively; P = 0.03), total-cholesterol (-18.4 ± 28.6 vs. +8.6±28.5 and -1.0±24.8 mg/dL; respectively; P = 0.004) and low density lipoproteins-(LDL)-cholesterol levels (-11.8±20.7 vs. +6.5 ±23.2 and -2.9±20.4 mg/dL, respectively; P = 0.01) was observed following the consumption of high-dose C. cyminum L. plus lime compared with low-dose C. cyminum L. plus lime and placebo. Conclusions: Results of the current study indicated that taking high-dose C. cyminum L. plus lime for eight weeks among subjects with overweight had beneficial effects on weight, BMI, FPG, QUICKI, triglycerides, total-cholesterol and LDL-cholesterol levels. © 2016, Iranian Red Crescent Medical Journal

The effects of curcumin on glycemic control and lipid profiles among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials

Background: This systematic review and meta-analysis of randomized controlled trials (RCTs), were performed to determine the effects of curcumin intake on glycemic control and lipid profiles among patients with metabolic syndrome (MetS) and related disorders. Methods: We searched the following databases up until January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and evaluated for quality of the studies in accordance with the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (MDs) with 95 confidence intervals (95 CI). Results: Twenty-six trials with 1890 participants were included in the current meta-analysis. The findings demonstrated the significant association between curcumin intake and reduced fasting glucose levels (SMD-0.78; 95 CI,-1.20,-0.37; P<0.001), homeostasis model of assessment-estimated insulin resistance (SMD-0.91; 95 CI,-1.52,-0.31; P=0.003) and HbA1c (SMD-0.92; 95 CI,-1.37,-0.47; P<0.001). In addition, curcumin supplementation was significantly associated with triglyceride (SMD-1.21; 95 CI,-1.78,-0.65; P<0.001) and total cholesterol reduction (SMD-0.73; 95 CI,-1.32,-0.13; P= 0.01). However, curcumin intake significantly increased insulin levels (SMD 0.92; 95 CI, 0.06, 1.78; P=0.036). We found no significant effect of curcumin supplementation on LDL-(SMD-0.52; 95 CI,-1.14, 0.11; P=0.10) and HDL-cholesterol levels (SMD 0.28; 95 CI,-0.22, 0.77; P=0.27). Conclusion: Overall, curcumin consumption was associated with a significant reduction in fasting glucose, HOMA-IR, HbA1c, triglycerides and total cholesterol levels among patients with MetS and related disorders, but did not affect LDL-and HDL-cholesterol levels. © 2018 Bentham Science Publishers

The Effects of Selenium Supplementation on Gene Expression Related to Insulin and Lipid Metabolism, and Pregnancy Outcomes in Patients with Gestational Diabetes Mellitus: a Randomized, Double-Blind, Placebo-Controlled Trial

This study was performed to evaluate the effects of selenium supplementation on gene expression related to insulin and lipid metabolism, and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). The current randomized, double-blind, placebo-controlled clinical trial was conducted in 36 patients with GDM. Participants were randomly divided into two groups to intake either 200 μg/day selenium supplements as selenium yeast or placebo (n = 18 each group) for 6 weeks. Selenium supplementation upregulated peroxisome proliferator-activated receptor gamma (P = 0.03) and glucose transporter 1 (GLUT-1) (P = 0.01) in lymphocytes of subjects with GDM compared with the placebo. Selenium supplementation did not affect gene expression of low-density lipoprotein receptor (LDLR) and lipoprotein(a) Lp(a). Supplementation with selenium had a significant decrease in incidence of newborns� hyperbilirubinemia (5.6% vs. 33.3%, P = 0.03) and newborns� hospitalization (5.6% vs. 33.3%, P = 0.03) compared with the placebo. Overall, we found that selenium supplementation for 6 weeks among patients with GDM significantly increased PPAR-γ and GLUT-1 expression, but did not affect gene expression of LDLR and LP(a). It also reduced incidence of newborns� hyperbilirubinemia and newborns� hospitalization. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N35. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

The Effects of Synbiotic Supplementation on Pregnancy Outcomes in Gestational Diabetes

Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidative actions. This study was designed to evaluate the effects of synbiotic administration on biomarkers of inflammation, oxidative stress, and pregnancy outcomes among gestational diabetic (GDM) women. This randomized, double-blind, placebo-controlled clinical trial was carried out among 60 subjects with GDM who were not on oral hypoglycemic agents. Patients were randomly assigned to consume either one synbiotic capsule containing Lactobacillus acidophilus strain T16 (IBRC-M10785), L. casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 � 10 9  CFU/g each) plus 800 mg inulin (HPX) (n = 30) or placebo (n = 30) for 6 weeks. Compared with the placebo, synbiotic supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (� 1.9 ± 4.2 vs. +1.1 ± 3.5 mg/L, P = 0.004), plasma malondialdehyde (MDA) (� 0.1 ± 0.6 vs. + 0.3 ± 0.7 μmol/L, P = 0.02), and significantly increased total antioxidant capacity (TAC) (+ 70.1 ± 130.9 vs. � 19.7 ± 124.6 mmol/L, P = 0.009) and total glutathione (GSH) levels (+ 28.7 ± 61.5 vs. � 14.9 ± 85.3 μmol/L, P = 0.02). Supplementation with synbiotic had a significant decrease in cesarean section rate (16.7 vs. 40.0, P = 0.04), lower incidence of hyperbilirubinemic newborns (3.3 vs. 30.0, P = 0.006), and newborns� hospitalization (3.3 vs. 30.0, P = 0.006) compared with the placebo. Synbiotic supplementation did not affect plasma nitric oxide (NO) levels and other pregnancy outcomes. Overall, synbiotic supplementation among GDM women for 6 weeks had beneficial effects on serum hs-CRP, plasma TAC, GSH, and MDA; cesarean section; incidence of newborn�s hyperbilirubinemia; and newborns� hospitalization but did not affect plasma NO levels and other pregnancy outcomes. http://www.irct.ir: www.irct.ir: IRCT201704205623N108. © 2017, Springer Science+Business Media, LLC

The Effects of Probiotic Supplementation on Clinical Symptom, Weight Loss, Glycemic Control, Lipid and Hormonal Profiles, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis of Randomized Controlled Trials

The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to determine the effectiveness of probiotic supplementation on clinical symptoms, weight loss, glycemic control, lipid and hormonal profiles, and biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome (PCOS). Eligible studies were systematically searched from Cochrane Library, Embase, Medline, and Web of Science databases until January 2019. Cochran (Q) and I-square statistics were used to measure heterogeneity among included studies. Data were pooled by using random-effect model and expressed as standardized mean difference (SMD) with 95 confidence interval (CI). Eleven articles were included in this meta-analysis. Probiotic supplementation significantly decreased weight (SMD � 0.30; 95 CI, � 0.53, � 0.07; P = 0.01), body mass index (BMI) (SMD � 0.29; 95 CI, � 0.54, � 0.03; P = 0.02), fasting plasma glucose (FPG) (SMD � 0.26; 95 CI, � 0.45, � 0.07; P < 0.001), insulin (SMD � 0.52; 95 CI, � 0.81, � 0.24; P < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (SMD � 0.53; 95 CI, � 0.79, � 0.26; P < 0.001), triglycerides (SMD � 0.69; 95 CI, � 0.99, � 0.39; P < 0.001), VLDL-cholesterol (SMD � 0.69; 95 CI, � 0.99, � 0.39; P < 0.001), C-reactive protein (CRP) (SMD � 1.26; 95 CI, � 2.14, � 0.37; P < 0.001), malondialdehyde (MDA) (SMD � 0.90; 95 CI, � 1.16, � 0.63; P < 0.001), hirsutism (SMD � 0.58; 95 CI, � 1.01, � 0.16; P < 0.001), and total testosterone levels (SMD � 0.58; 95 CI, � 0.82, � 0.34; P < 0.001), and also increased the quantitative insulin sensitivity check index (QUICKI) (SMD 0.41; 95 CI, 0.11, 0.70; P < 0.01), nitric oxide (NO) (SMD 0.33; 95 CI 0.08, 0.59; P = 0.01), total antioxidant capacity (TAC) (SMD 0.64; 95 CI, 0.38, 0.90; P < 0.001), glutathione (GSH) (SMD 0.26; 95 CI, 0.01, 0.52; P = 0.04), and sex hormone binding globulin (SHBG) levels (SMD 0.46; 95 CI, 0.08, 0.85; P = 0.01). Probiotic supplementation may result in an improvement in weight, BMI, FPG, insulin, HOMA-IR, triglycerides, VLDL-cholesterol, CRP, MDA, hirsutism, total testosterone, QUICKI, NO, TAC, GSH, and SHBG but did not affect dehydroepiandrosterone sulfate levels, and total, LDL, and HDL cholesterol levels in patients with PCOS. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Effects of probiotic supplementation on hormonal profiles, biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial

Background: To the best of our knowledge, data on effects of probiotic administration on hormonal profiles, biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome (PCOS) are scarce. This investigation was conducted to assess the effects of probiotic supplementation on hormonal profiles, biomarkers of inflammation and oxidative stress in women with PCOS. Methods: This randomized, double-blind, placebo-controlled trial was conducted on 60 women with PCOS, aged 18-40 years old. Subjects were randomly assigned into 2 groups to receive either probiotics or placebo (n = 30 each group) for 12 weeks. Metabolic profiles were quantified at baseline and after a 12-week intervention. Results: After the 12-week intervention, compared with placebo, probiotic supplementation significantly increased serum sex hormone-binding globulin (SHBG) (+25.9 ± 32.5 vs. +0.5 ± 15.6 nmol/L, P < 0.001) and plasma total antioxidant capacity (TAC) (+8.8 ± 120.5 vs. -98.3 ± 246.4 mmol/L, P = 0.04), and significantly decreased serum total testosterone (-0.2 ± 0.7 vs. +0.2 ± 0.6 ng/mL, P = 0.03), modified Ferriman-Gallwey (mF-G) scores (-1.7 ± 1.5 vs. -0.2 ± 1.0, P < 0.001), serum high-sensitivity C-reactive protein (hs-CRP) (-1150.0 ± 1295.2 vs. +202.5 ± 1426.3 ng/mL, P < 0.001) and plasma malondialdehyde (MDA) concentrations (-0.2 ± 0.6 vs. +0.9 ± 1.3 µmol/L, P < 0.001). We did not observe any detrimental effect of probiotic supplementation on other metabolic profiles. Conclusion: Overall, probiotic supplementation of PCOS women for 12 weeks had beneficial effects on total testosterone, SHBG, mFG scores, hs-CRP, TAC and MDA levels but did not affect other metabolic profiles. © 2018 The Author(s)

The effects of Vitamin D and omega-3 fatty acids co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in patients with gestational diabetes

Background: This study was carried out to determine the effects of vitamin D and omega-3 fatty acids co- supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in gestational diabetes (GDM) patients. Methods: This randomized, double-blind, placebo-controlled trial was conducted among 120 GDM women. Participants were randomly divided into four groups to receive: 1) 1000 mg omega-3 fatty acids containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) twice a day + vitamin D placebo (n = 30); 2) 50,000 IU vitamin D every 2 weeks + omega-3 fatty acids placebo (n = 30); 3) 50,000 IU vitamin D every 2 weeks + 1000 mg omega-3 fatty acids twice a day (n = 30) and 4) vitamin D placebo + omega-3 fatty acids placebo (n = 30) for 6 weeks. Results: Subjects who received vitamin D plus omega-3 fatty acids supplements compared with vitamin D, omega-3 fatty acids and placebo had significantly decreased high-sensitivity C-reactive protein (-2.0 ± 3.3 vs. -0.8 ± 4.4, -1.3 ± 2.4 and +0.9 ± 2.7 mg/L, respectively, P = 0.008), malondialdehyde (-0.5 ± 0.5 vs. -0.2 ± 0.5, -0.3 ± 0.9 and +0.5 ± 1.4 μmol/L, respectively, P < 0.001), and increased total antioxidant capacity (+92.1 ± 70.1 vs. +55.1 ± 123.6, +88.4 ± 95.2 and +1.0 ± 90.8 mmol/L, respectively, P = 0.001) and glutathione (+95.7 ± 86.7 vs. +23.0 ± 62.3, +30.0 ± 66.5 and -7.8 ± 126.5 μmol/L, respectively, P = 0.001). In addition, vitamin D and omega-3 fatty acids co-supplementation, compared with vitamin D, omega-3 fatty acids and placebo, resulted in lower incidences of newborns' hyperbilirubinemiain (P = 0.037) and newborns' hospitalization (P = 0.037). Conclusion: Overall, vitamin D and omega-3 fatty acids co-supplementation for 6 weeks among GDM women had beneficial effects on some biomarkers of inflammation, oxidative stress and pregnancy outcomes. © 2017 The Author(s)

The effects of Vitamin D and omega-3 fatty acids co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in patients with gestational diabetes

Background: This study was carried out to determine the effects of vitamin D and omega-3 fatty acids co- supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in gestational diabetes (GDM) patients. Methods: This randomized, double-blind, placebo-controlled trial was conducted among 120 GDM women. Participants were randomly divided into four groups to receive: 1) 1000 mg omega-3 fatty acids containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) twice a day + vitamin D placebo (n = 30); 2) 50,000 IU vitamin D every 2 weeks + omega-3 fatty acids placebo (n = 30); 3) 50,000 IU vitamin D every 2 weeks + 1000 mg omega-3 fatty acids twice a day (n = 30) and 4) vitamin D placebo + omega-3 fatty acids placebo (n = 30) for 6 weeks. Results: Subjects who received vitamin D plus omega-3 fatty acids supplements compared with vitamin D, omega-3 fatty acids and placebo had significantly decreased high-sensitivity C-reactive protein (-2.0 ± 3.3 vs. -0.8 ± 4.4, -1.3 ± 2.4 and +0.9 ± 2.7 mg/L, respectively, P = 0.008), malondialdehyde (-0.5 ± 0.5 vs. -0.2 ± 0.5, -0.3 ± 0.9 and +0.5 ± 1.4 μmol/L, respectively, P < 0.001), and increased total antioxidant capacity (+92.1 ± 70.1 vs. +55.1 ± 123.6, +88.4 ± 95.2 and +1.0 ± 90.8 mmol/L, respectively, P = 0.001) and glutathione (+95.7 ± 86.7 vs. +23.0 ± 62.3, +30.0 ± 66.5 and -7.8 ± 126.5 μmol/L, respectively, P = 0.001). In addition, vitamin D and omega-3 fatty acids co-supplementation, compared with vitamin D, omega-3 fatty acids and placebo, resulted in lower incidences of newborns' hyperbilirubinemiain (P = 0.037) and newborns' hospitalization (P = 0.037). Conclusion: Overall, vitamin D and omega-3 fatty acids co-supplementation for 6 weeks among GDM women had beneficial effects on some biomarkers of inflammation, oxidative stress and pregnancy outcomes. © 2017 The Author(s)