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Effect of Rosuvastatin on Cholesterol Efflux Capacity and Endothelial Function in Type 2 Diabetes Mellitus and Dyslipidemia.
Jung, KY, Kim, KM, Han, SK, Yun, HM, Oh, TJ, Choi, SH, Park, KS, Jang, HC, Lim, S
Circulation journal : official journal of the Japanese Circulation Society. 2018;(5):1387-1395
Abstract
BACKGROUND Quality and quantity of high-density lipoprotein cholesterol (HDL-C) may be associated with cardiovascular risk. We investigated the effect of rosuvastatin on cholesterol efflux (CE) for HDL function and vascular health.Methods and Results:We enrolled 30 dyslipidemic patients with type 2 diabetes mellitus and 20 healthy subjects as controls. Vascular health was assessed on flow-medicated dilation (FMD), nitroglycerin-induced dilatation of the brachial artery and carotid artery intima-media thickness (cIMT). These parameters were compared between patients and controls, and between baseline and at 12 weeks of treatment with rosuvastatin 20 mg. Age and body mass index were 49.8±11.3 years and 25.8±3.7 kg/m2in the patients, and 28.8±3.2 years and 22.4±2.4 kg/m2in the controls, respectively. The biomarkers related to lipid and glucose metabolism and lipoprotein (a), high-sensitivity C-reactive protein, and cIMT were significantly higher, and CE and FMD were significantly lower in the patients than in the controls. In the patients, rosuvastatin 20 mg decreased low-density lipoprotein cholesterol by 54.1% and increased HDL-C by 4.8%. The CE increased significantly after rosuvastatin treatment (12.26±2.72% vs. 14.05±4.14%). FMD also increased, and lipoprotein (a) and cIMT decreased significantly and were associated with changes of CE. CONCLUSIONS Rosuvastatin-induced changes in HDL function are significantly associated with cardiovascular benefit.
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The effects of coenzyme Q10 supplementation on gene expression related to insulin, lipid and inflammation in patients with polycystic ovary syndrome.
Rahmani, E, Jamilian, M, Samimi, M, Zarezade Mehrizi, M, Aghadavod, E, Akbari, E, Tamtaji, OR, Asemi, Z
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2018;(3):217-222
Abstract
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.
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In vitro evaluation of the toxic effects of MgO nanostructure in Hela cell line.
Akram, MW, Fakhar-E-Alam, M, Atif, M, Butt, AR, Asghar, A, Jamil, Y, Alimgeer, KS, Wang, ZM
Scientific reports. 2018;(1):4576
Abstract
MgO is an attractive choice for carcinogenic cell destruction in photodynamic therapy, as confirmed by manifold analysis. The prime focus of the presented research is to investigate the toxicity caused by morphologically different MgO nanostructures obtained by annealing at various annealing temperatures. Smart (stimuli-responsive) MgO nanomaterials are a very promising class of nanomaterials, and their properties can be controlled by altering their size, morphology, or other relevant characteristics. The samples investigated here were grown by the co-precipitation technique. Toxicity-dependent parameters were assessed in a HeLa cell model after annealing the grown samples at 350 °C, 450 °C, and 550 °C. After the overall characterization, an analysis of toxicity caused by changes in the MgO nanostructure morphology was tested in a HeLa cell model using a neutral red assay and microscopy. The feasibility of using MgO for PDT was assessed. Empirical modelling was applied to corroborate the experimental results obtained from assessing cell viability losses and reactive oxygen species. The results indicate that MgO is an excellent candidate material for medical applications and could be utilized for its potential ability to upgrade conventionally used techniques.
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Magnesium-Zinc-Calcium-Vitamin D Co-supplementation Improves Hormonal Profiles, Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.
Maktabi, M, Jamilian, M, Asemi, Z
Biological trace element research. 2018;(1):21-28
Abstract
Data on the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS) are scarce. The objective of this study was to assess the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress in women with PCOS. Sixty PCOS women were randomized into two groups and treated with 100 mg magnesium, 4 mg zinc, 400 mg calcium plus 200 IU vitamin D supplements (n = 30), or placebo (n = 30) twice a day for 12 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were assessed at baseline and at end-of-treatment. After the 12-week intervention, compared with the placebo, magnesium-zinc-calcium-vitamin D co-supplementation resulted in significant reductions in hirsutism (-2.4 ± 1.2 vs. -0.1 ± 0.4, P < 0.001), serum high sensitivity C-reactive protein (-0.7 ± 0.8 vs. +0.2 ± 1.8 mg/L, P < 0.001), and plasma malondialdehyde (-0.4 ± 0.3 vs. +0.2 ± 1.0 μmol/L, P = 0.01), and a significant increase in plasma total antioxidant capacity concentrations (+46.6 ± 66.5 vs. -7.7 ± 130.1 mmol/L, P = 0.04). We failed to find any significant effect of magnesium-zinc-calcium-vitamin D co-supplementation on free androgen index, and other biomarkers of inflammation and oxidative stress. Overall, magnesium-zinc-calcium-vitamin D co-supplementation for 12 weeks among PCOS women had beneficial effects on hormonal profiles, biomarkers of inflammation, and oxidative stress.
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High-dose ω-3 Fatty Acid Plus Vitamin D3 Supplementation Affects Clinical Symptoms and Metabolic Status of Patients with Multiple Sclerosis: A Randomized Controlled Clinical Trial.
Kouchaki, E, Afarini, M, Abolhassani, J, Mirhosseini, N, Bahmani, F, Masoud, SA, Asemi, Z
The Journal of nutrition. 2018;(8):1380-1386
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Abstract
BACKGROUND Combined omega-3 fatty acid and vitamin D supplementation may improve multiple sclerosis (MS) by correcting metabolic abnormalities and attenuating oxidative stress and inflammation. OBJECTIVE This study aimed to determine the effects of ω-3 fatty acid and vitamin D cosupplementation on the disability score and metabolic status of patients with MS. METHODS This was a randomized, placebo-controlled clinical trial with Expanded Disability Status Scale (EDSS) score and inflammation as primary outcomes and oxidative stress biomarkers and metabolic profile as secondary outcomes. Patients, aged 18-55 y, were matched for disease EDSS scores, gender, medications, BMI, and age (n = 53) and randomly received a combined 2 × 1000 mg/d ω-3 fatty acid and 50,000 IU/biweekly cholecalciferol supplement or placebo for 12 wk. The placebos were matched in colour, shape, size, packaging, smell, and taste with supplements. Fasting blood samples were collected at baseline and end of intervention to measure different outcomes. Multiple linear regression models were used to assess treatment effects on outcomes adjusting for confounding variables. RESULTS Patients taking ω-3 fatty acid plus vitamin D supplements showed a significant improvement in EDSS (β -0.18; 95% CI: -0.33, -0.04; P = 0.01), compared with placebo. Serum high-sensitivity C-reactive protein (β -1.70 mg/L; 95% CI: -2.49, -0.90 mg/L; P < 0.001), plasma total antioxidant capacity (β +55.4 mmol/L; 95% CI: 9.2, 101.6 mmol/L; P = 0.02), total glutathione (β +51.14 µmol/L; 95% CI: 14.42, 87.87 µmol/L; P = 0.007), and malondialdehyde concentrations (β -0.86 µmol/L; 95% CI: -1.10, -0.63 µmol/L; P < 0.001) were significantly improved in the supplemented group compared with the placebo group. In addition, ω-3 fatty acid and vitamin D cosupplementation resulted in a significant reduction in serum insulin, insulin resistance, and total/HDL-cholesterol, and a significant increase in insulin sensitivity and serum HDL-cholesterol concentrations. CONCLUSION Overall, taking ω-3 fatty acid and vitamin D supplements for 12 wk by patients with MS had beneficial effects on EDSS and metabolic status. This trial was registered at the Iranian website (www.irct.ir) for registration of clinical trials as IRCT2017090133941N20.
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Rett-like Severe Encephalopathy Caused by a De Novo GRIN2B Mutation Is Attenuated by D-serine Dietary Supplement.
Soto, D, Olivella, M, Grau, C, Armstrong, J, Alcon, C, Gasull, X, Gómez de Salazar, M, Gratacòs-Batlle, E, Ramos-Vicente, D, Fernández-Dueñas, V, et al
Biological psychiatry. 2018;(2):160-172
Abstract
BACKGROUND N-Methyl-D-aspartate receptors (NMDARs) play pivotal roles in synaptic development, plasticity, neural survival, and cognition. Despite recent reports describing the genetic association between de novo mutations of NMDAR subunits and severe psychiatric diseases, little is known about their pathogenic mechanisms and potential therapeutic interventions. Here we report a case study of a 4-year-old Rett-like patient with severe encephalopathy carrying a missense de novo mutation in GRIN2B(p.P553T) coding for the GluN2B subunit of NMDAR. METHODS We generated a dynamic molecular model of mutant GluN2B-containing NMDARs. We expressed the mutation in cell lines and primary cultures, and we evaluated the putative morphological, electrophysiological, and synaptic plasticity alterations. Finally, we evaluated D-serine administration as a therapeutic strategy and translated it to the clinical practice. RESULTS Structural molecular modeling predicted a reduced pore size of mutant NMDARs. Electrophysiological recordings confirmed this prediction and also showed gating alterations, a reduced glutamate affinity associated with a strong decrease of NMDA-evoked currents. Moreover, GluN2B(P553T)-expressing neurons showed decreased spine density, concomitant with reduced NMDA-evoked currents and impaired NMDAR-dependent insertion of GluA1 at stimulated synapses. Notably, the naturally occurring coagonist D-serine was able to attenuate hypofunction of GluN2B(p.P553T)-containing NMDARs. Hence, D-serine dietary supplementation was initiated. Importantly, the patient has shown remarkable motor, cognitive, and communication improvements after 17 months of D-serine dietary supplementation. CONCLUSIONS Our data suggest that hypofunctional NMDARs containing GluN2B(p.P553T) can contribute to Rett-like encephalopathy and that their potentiation by D-serine treatment may underlie the associated clinical improvement.
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Effect of educational interventions on health in childhood: A meta-analysis of randomized controlled trials.
Wang, X, Zhou, G, Zeng, J, Yang, T, Chen, J, Li, T
Medicine. 2018;(36):e11849
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BACKGROUND The purpose of this study was to summarize the evidences from randomized controlled trials (RCTs) investigating the effects of educational interventions in overweight/obesity childhood by using meta-analytic approach. METHODS PubMed, Embase, and the Cochrane Library databases were searched from the inception to April 2018. Weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were used to measure the effects of educational interventions during childhood in the random-effects models. RESULTS Thirty RCTs reporting data on 35,296 children were included in the meta-analysis. The summary WMD indicated that children received educational interventions had lower levels of body mass index (BMI) (WMD: -0.15; 95% CI: -0.24 to -0.05; P = .003), BMI z-score (WMD: -0.03; 95% CI: -0.05 to -0.02; P < .001), waist circumference (WMD: -0.97; 95% CI: -1.95 to -0.00; P = 0.050), triceps skinfold (WMD: -1.39; 95% CI: -2.41 to -0.37; P = .008), systolic blood pressure (WMD: -1.13; 95% CI: -2.20 to -0.07; P = .037), total cholesterol (WMD: -4.04; 95% CI: -7.18 to -0.90; P = .012), and triglyceride (WMD: -2.62; 95% CI: -4.33 to -0.90; P = .003). However, educational interventions were not associated with the levels of waist-to-hip ratio, diastolic blood pressure, high-density lipoprotein, and low-density lipoprotein. CONCLUSION The study findings elucidate the positive effects of educational interventions on BMI, BMI z-score, waist circumference, triceps skinfold, systolic blood pressure, total cholesterol, and triglyceride.
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Long-term effects of combined simvastatin and metformin treatment on the clinical abnormalities and ovulation dysfunction in single young women with polycystic ovary syndrome.
Seyam, E, Hefzy, E
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2018;(12):1073-1080
Abstract
The aim of the current work was to investigate the value of the long term effects of combined use of simvastatin and metformin treatment for a year versus the effects of their individual treatment on the clinical, biochemical abnormalities, and ovulation dysfunction in young single women with polycystic ovary syndrome (PCOS). It was a randomized, double-blind controlled study. Where two hundreds (n = 200) single young women with PCOS were randomized into seventy (n = 70) women using simvastatin 20 mg daily combined with metformin 500 mg three times daily considered as group A (study group), and another 2 sixty five (n = 65) women groups using simvastatin and metformin individually as a single treatment use, and considered as groups (B & C), respectively. Medications period extended for twelve months treatment period. The primary outcome measures were the changes in serum androgen levels (testosterone, androstendione, and dehydro-epiandrostenion sulfate-DHEAS), LH, FSH, LH/FSH ratio, and insulin resistance (IR), in addition to menstrual regularity, hirsutism, BMI, and W/H ratio. Spontaneous ovulation, confirmed with both trans-abdominal sonography (TAS) and luteal serum progesterone as well had been also evaluated. After 12 months' treatment, in group A serum testosterone showed significant decline by 37%, with significant drop in LH serum level (51%) and a marked decline of the LH/FSH ratio (53%). IR showed a significant improvement in groups A and C but still relatively higher in group B. There was also a clear decrease of total cholesterol (36%), low-density lipoprotein (LDL; 48%), and triglycerides (26%), and increased high-density lipoprotein (HDL) by 24% in groups A and B. Improved menstrual regularity and decreased hirsutism, acne, ovarian volume, and BMI had been significantly noticed in the study groups A and C, although still relatively higher in group C. Spontaneous ovulation had been confirmed in group A: songoraphically (TAS), and biochemically (progesterone >10 ng) in 10 women after the first six months treatment, and 26 at the end of 12 months treatment, compared to 5 & 8 in group B, and 2 & 5 in group C, respectively. Combined simvastatin and metformin treatment showed significant improvement of PCOS clinical and ovarian dysfunction abnormalities much better than their individual treatment.
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Comparative study of cyto- and genotoxic potential with mechanistic insights of tungsten oxide nano- and microparticles in lung carcinoma cells.
Chinde, S, Poornachandra, Y, Panyala, A, Kumari, SI, Yerramsetty, S, Adicherla, H, Grover, P
Journal of applied toxicology : JAT. 2018;(6):896-913
Abstract
The exigency of semiconductor and super capacitor tungsten oxide nanoparticles (WO3 NPs) is increasing in various sectors. However, limited information on their toxicity and biological interactions are available. Hence, we explored the underlying mechanisms of toxicity induced by WO3 NPs and their microparticles (MPs) using different concentrations (0-300 μg ml-1 ) in human lung carcinoma (A549) cells. The mean size of WO3 NPs and MPs by transmission electron microscopy was 53.84 nm and 3.88 μm, respectively. WO3 NPs induced reduction in cell viability, membrane damage and the degree of induction was size- and dose-dependent. There was a significant increase in the percentage tail DNA and micronuclei formation at 200 and 300 μg ml-1 after 24 hours of exposure. The DNA damage induced by WO3 NPs could be attributed to increased oxidative stress and inflammation through reactive oxygen species generation, which correlated with the depletion of reduced glutathione content, catalase and an increase in malondialdehyde levels. Cellular uptake studies unveiled that both the particles were attached/surrounded to the cell membrane according to their size. In addition, NP inhibited the progression of the cell cycle in the G2 /M phase. Other studies such as caspase-9 and -3 and Annexin-V-fluorescein isothiocyanate revealed that NPs induced intrinsic apoptotic cell death at 200 and 300 μg ml-1 concentrations. However, in comparison to NPs, WO3 MPs did not incite any toxic effects at the tested concentrations. Under these experimental conditions, the no-observed-significant-effect level of WO3 NPs was determined to be ≤200 μg ml-1 in A549 cells.
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Positive Effects against UV-A Induced Damage and Oxidative Stress on an In Vitro Cell Model Using a Hyaluronic Acid Based Formulation Containing Amino Acids, Vitamins, and Minerals.
Stellavato, A, Pirozzi, AVA, Donato, S, Scognamiglio, I, Reale, S, Di Pardo, A, Filosa, S, Vassallo, V, Bellia, G, De Rosa, M, et al
BioMed research international. 2018;:8481243
Abstract
Ultraviolet (UV) radiations are responsible for skin photoaging inducing alteration of the molecular and cellular pathways resulting in dryness and reduction of skin elasticity. In this study, we investigated, in vitro, the antiaging and antioxidant effects of hyaluronan formulations based hydrogel. Skinkò E, an intradermic formulation composed of hyaluronic acid (HA), minerals, amino acids, and vitamins, was compared with the sole HA of the same size. For this purpose, HaCaT cells were subjected to UV-A radiations and H2O2 exposure and then treated with growth medium (CTR) combined with M-HA or Skinkò E to evaluate their protective ability against stressful conditions. Cells reparation was evaluated using a scratch in vitro model and Time-Lapse Video Microscopy. A significant protective effect for Skinkò E was shown with respect to M-HA. In addition, Skinkò E increased cell reparation. Therefore, NF-kB, SOD-2, and HO-1 were significantly reduced at the transcriptional and protein level. Interestingly, γ-H2AX and protein damage assay confirmed the protection by hyaluronans tested against oxidative stress. G6pdΔ ES cell line, highly susceptible to oxidative stress, was used as a further cellular model to assess the antioxidant effect of Skinkò E. Western blotting analyses showed that the treatment with this new formulation exerts marked antioxidant action in cells exposed to UV-A and H2O2. Thus, the protective and reparative properties of Skinkò E make it an interesting tool to treat skin aging.