Oligopin® Supplementation Mitigates Oxidative Stress in Postmenopausal Women with Osteopenia: A Randomized, Double-blind, Placebo-Controlled Trial.

BACKGROUND: Evidence indicates a close association between oxidative stress and the etiopathogenesis of osteopenia. In vitro and animal studies report that Oligopin®, an extract of French maritime pine bark extract, has beneficial effects on oxidative stress. PURPOSE: Here, we aimed to determine whether supplementation with Oligopin® affects bone turnover markers, antioxidant enzymes, and oxidative stress markers in these patients. METHODS: Forty-three postmenopausal women with osteopenia were randomized in a placebo-controlled, double-blind clinical trial to receive either 150 mg/day Oligopin® (n = 22) or placebo (n = 21) for 12 weeks. Plasma levels of bone turnover markers; osteocalcin (OC), type I collagen cross-linked C-telopeptide (CTX-1), OC/CTX1 ratio along with total antioxidant capacity(TAC), malondialdehyde (MDA) concentration, protein carbonyl, and total thiol contents in plasma, activities of manganese superoxide dismutase (MnSOD) and catalase in both peripheral blood mononuclear cells (PBMCs) and plasma as well as mRNA expression of MnSOD, catalase, and Nrf2 in PBMCs were measured at the baseline and the end of the intervention. RESULTS: Oligopin® supplementation significantly increased OC levels and the ratio of OC to CTX1 in women with osteopenia compared to placebo intervention after 12 weeks. Oligopin® significantly decreased plasma protein carbonyl content in postmenopausal women compared with the after placebo treatment. Moreover, Oligopin® intervention significantly increased plasma total thiol content, TAC, plasma activity of both MnSOD and catalase, and the transcript level of Nrf2, MnSOD, and catalase in comparison with the placebo group. CONCLUSION: Supplementation with 150 mg/day Oligopin® for 12 weeks exerts beneficial effects in postmenopausal osteopenia through improving the antioxidant defense system in the plasma and PBMCs that was accompanied by an increase in indicators of bone turnover.

Differential expressions of SIRT1, SIRT3, and SIRT4 in peripheral blood mononuclear cells from patients with type 2 diabetic retinopathy.

This study investigated the mRNA and protein levels of SIRT1, SIRT3, and SIRT4 in peripheral blood mononuclear cells (PBMCs) from type 2 diabetes patients with retinopathy (diabetic retinopathy (DR) patients) (n = 86) and those without retinopathy (n = 103). The mRNA expression of SIRT1 and SIRT3 was found to be significantly higher in diabetic patients with retinopathy compared to those without retinopathy. Notably, protein levels of SIRT1, SIRT3, and SIRT4 were higher in patients with DR compared with controls after adjusting for diabetes duration and taking metformin (p = .001 for SIRT1; p = .001 for SIRT3; p = .005 for SIRT4). In the logistic model, there was a significant association between SIRT3 and DR (p = .0001) independent of age and sex and hyperglycaemia markers including FBS, HbA1c, and diabetic duration. These findings suggest an emerging role of sirtuins in the pathogenesis of retinopathy, but further studies are necessary to establish this concept.

Effects of French maritime pine bark extract (Oligopin®) supplementation on bone remodeling markers in postmenopausal osteopenic women: A randomized clinical trial.

French maritime pine bark extract (FMPBE; Oligopin®), a dietary supplement, is rich in procyanidin. The objective of this study was to determine the effects of FMPBE on bone remodeling in postmenopausal osteopenic women. This randomized, double-blinded, placebo-controlled clinical trial was conducted on 40 postmenopausal osteopenic women. Individuals were randomly assigned to either FMPBE (250 mg/day, n = 21) or placebo (250-mg starch/day, n = 19) for 12 weeks. Biochemical indices, including bone remodeling marker, were assessed before and after the intervention. After the 12-week intervention, that is, FMPBE supplementation, a significant increase in bone alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) levels and a significant decrease in C-terminal telopeptide of type I collagen (CTx1) were observed. Compared with the control group, FMPBE supplementation resulted in a significant increase in P1NP (0.015), BAP levels (0.001), and BAP/CTx1 ratio (p = 0.001) and a significant decrease in CTx1 levels (0.006). FMPBE supplementation for 12 weeks in postmenopausal osteopenic women produced favorable effects on bone markers. Meanwhile, further research is needed to determine whether FMPBE supplements can be used as a preventive strategy for bone loss in postmenopausal osteopenic women.

Possible association between circulating CTRP3 and knee osteoarthritis in postmenopausal women.

BACKGROUND: Osteoarthritis (OA) is considered as one of the most common cause of chronic pain and functional disabilities in the elderly. AIM: To examine serum levels of complement-C1q TNF-related protein 3 (CTRP3) in postmenopausal women with knee OA. METHODS: A population-based cross-sectional study was performed in women who complained of chronic knee pain. All subjects were followed by clinical and weight-bearing bilateral anteroposterior radiographical examinations. The Kellgren and Lawrence (K&L) score was used for knee OA classification. Two groups of postmenopausal women were chosen to investigate CTRP3 as an OA marker who had the K&L score ≥ 3 as a case group and K&L ≤ 1 as a control group. Serum levels of CTRP3 were measured in two groups. RESULTS: According to K&L classification, 36 subjects with knee OA and 54 age-matched without or mild OA were selected. After adjusting the obtained data for taking NSAID drugs, the concentration of Ln CTRP3 in serum of patients with OA was lower compared to control group [mean ± SE, (0.39 ± 0.05 ng/ml vs. 0.48 ± 0.03 ng/ml, respectively, p = 0.04)]. DISCUSSION: There is a possible role for CTRP3 as an anti-inflammatory mediator in knee OA in postmenopausal women. CONCLUSIONS: Our results indicate an association between CTRP3 and knee OA. However, a much more robust study is required to draw that circulating CTRP3 could be a clinical marker for osteoarthritis.

Air pollution during pregnancy and placental adaptation in the levels of global DNA methylation.

BACKGROUND: Health in early life is crucial for health later in life. Exposure to air pollution during embryonic and early-life development can result in placental epigenetic modification and foetus reprogramming, which can influence disease susceptibility in later life. Objectives: The aim of this paper was to investigate the placental adaptation in the level of global DNA methylation and differential gene expression in the methylation cycle in new-borns exposed to high fine particulate matter in the foetal stage. STUDY DESIGN: This is a nested case-control study. We enrolled pregnant healthy women attending prenatal care clinics in Tehran, Iran, who were residents of selected polluted and unpolluted regions, before the 14th week of pregnancy. We calculated the regional background levels of particle mass- particles with aerodynamics diameter smaller than 2.5 µm (PM2.5) and 10 µm (PM10)-of two regions of interest. At the time of delivery, placental tissue was taken for gene expression and DNA methylation analyses. We also recorded birth outcomes (the new-born's sex, birth date, birth weight and length, head and chest circumference, gestational age, Apgar score, and level of neonatal care required). RESULTS: As regards PM2.5 and PM10 concentrations in different time windows of pregnancy, there were significantly independent positive correlations between PM10 and PM2.5 in the first trimester of all subjects and placental global DNA methylation levels (p-value = 0.01, p-value = 0.03, respectively). The gene expression analysis showed there was significant correlation between S-adenosylmethionine expression and PM2.5 (p = 0.003) and PM10 levels in the first trimester (p = 0.03). CONCLUSION: Our data showed prenatal exposures to air pollutants in the first trimester could influence placental adaptation by DNA methylation.

Direct costs of osteoporosis-related hip fractures: protocol for a cross-sectional analysis of a national database.

INTRODUCTION: It is estimated that Iran accounted for about 1% of hip fracture burden of the world in 2007, but these data are based on incomplete evidence. As the country's population is ageing, it is expected that a dramatic rise in hip fracture incidence will result. There is no single national study that accurately estimates the incidence of all hip fractures in the country or identifies the direct costs for affected patients. To help fill this gap, the current study has been designed to determine the incidence of hip fracture associated with osteoporosis in the Iranian population and to assess the direct costs involved. METHODS AND ANALYSIS: This is a cross-sectional analysis of 2 years of hospital admissions due to hip fracture in Iran from October 2014 to October 2016 using an electronic health record called SEPAS. SEPAS is a nationwide health information system established by Information Technology (IT) and the Statistics Department of the Ministry of Health. SEPAS has recorded more than 8.5 million inpatient hospitalizations since October 2014. Our study will identify reported hip fracture data in SEPAS among admitted adult hospital patients aged ≥50 in Iran. International Classification of Diseases ICD-9 and 10 will be used as diagnostic codes. Study factors are demographic data, types of fracture, types of treatment, duration of admission, early complications, in-hospital mortality and direct cost of fracture treatment. The accuracy of the SEPAS fracture data will be ascertained through a pilot study that compares the SEPAS data with the data directly extracted from medical records of the Shariati Hospital in Tehran during the study period. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the National Institute for Medical Research Development of Iran. Dissemination plans include academic publications, conference presentations and social media.

Impact of air pollution on vitamin D deficiency and bone health in adolescents.

The association between air pollution and bone health was evaluated in adolescents in the city of Tehran. This study is essentially ecological. Vitamin D deficiency among adolescents has been reported at higher rates in polluted areas than in non-polluted areas. Additionally, residence in polluted areas is associated with lower levels of bone alkaline phosphatase. PURPOSE: The aim of this study was to evaluate the association between ambient air pollution and bone turnover in adolescents and to compare the prevalence of vitamin D deficiency between polluted and non-polluted areas of Tehran. METHODS: This cross-sectional population-based study was conducted on 325 middle- and high-school students (both girls and boys) in Tehran in the winter. During the study period, detailed daily data on air pollution were obtained from archived data collected by Tehran Air Quality Control Company (AQCC). Serum levels of calcium, phosphorus, parathyroid hormone (PTH), bone-specific alkaline phosphatase, 25(OH) vitamin D, osteocalcin, cross-linked C-telopeptide (CTX), total protein, albumin, and creatinine were obtained from the study group. RESULTS: Vitamin D deficiency was more prevalent in polluted areas than in non-polluted areas. After adjustment for age and sex, residence in the polluted area showed a statistically significant positive association with vitamin D deficiency and a statistically significant negative association with bone turnover. Interestingly, high calcium intake (>5000 mg/week) protects against the effects of air pollution on bone turnover. CONCLUSIONS: Air pollution is a chief factor determining the amount of solar UVB that reaches the earth's surface. Thus, atmospheric pollution may play a significant independent role in the development of vitamin D deficiency.

Epigenetic Alterations and Exposure to Air Pollutants: Protocol for a Birth Cohort Study to Evaluate the Association Between Adverse Birth Outcomes and Global DNA Methylation.

BACKGROUND: Prenatal exposure to air pollutants can increase the risk of adverse birth outcomes and susceptibility to a number of complex disorders later in life. Despite this general understanding, the molecular and cellular responses to air pollution exposure during early life are not completely clear. OBJECTIVE: The aims of this study are to test the association between air pollution and adverse pregnancy outcomes, and to determine whether the levels of maternal and cord blood and of placental DNA methylation during pregnancy predict adverse birth outcomes in polluted areas. METHODS: This is a birth cohort study. We will enroll pregnant healthy women attending prenatal care clinics in Tehran, Iran, who are resident in selected polluted and unpolluted regions before the 14th week of pregnancy. We will calculate the regional background levels of fine particulate matter (particles with a diameter between 2.5 and 10 µm) and nitrogen dioxide for all regions of by using data from the Tehran Air Quality Control Company. Then, we will select 2 regions as the polluted and unpolluted areas of interest. Healthy mothers living in the selected polluted and non polluted regions will be enrolled in this study. A maternal health history questionnaire will be completed at each trimester. During the first and second trimester, we will draw mothers' blood for biochemical and DNA methylation analyses. At the time of delivery time, we will collect maternal and cord blood for biochemical, gene expression, and DNA methylation analyses. We will also record birth outcomes (the newborn's sex, birth date, birth weight and length, gestational age, Apgar score, and level of neonatal care required). RESULTS: The project was funded in March 2016 and enrollment will be completed in August 2017. Data analysis is under way, and the first results are expected to be submitted for publication in November 2017. CONCLUSIONS: We supposed that prenatal exposures to air pollutants can influence fetal reprogramming by epigenetic modifications such as DNA methylation. This could explain the association between air pollution and adverse pregnancy outcomes.

New insight into determining indicators of metabolic status in women: Expression of PPARγ and FABP4 in PBMCs.

Adiposity and its metabolic disturbances could be regulated by adipocyte-specific peroxisome proliferator-activated receptor gamma and fatty acid-binding protein4. Although these two proteins are mainly expressed in adipose tissues, they can also be expressed in peripheral blood mononuclear cells, which could be useful for predicting body composition and blood parameters. Thus, this cross-sectional study was performed during January 2013-January 2014 with 229 women (age range, 22-52 years) who were classified as obese or nonobese. Serum glucose, insulin, lipids, and body composition were measured in the fasting state. Peripheral blood mononuclear cells were isolated to extract ribonucleic acid (RNA) and to determine gene expression by real time polymerase chain reaction (PCR). All serum parameters and components of body composition were significantly higher in obese than in nonobese women. Gene expression analysis showed that serum levels of glucose and lipids, except high-density lipoprotein (HDL), were higher in the group that expressed high fatty acid-binding protein4. Increased expression of the peroxisome proliferator-activated receptor gamma was associated with a significant reduction of blood sugar and increased HDL and other lipids and visceral fat. Therefore, it seems that the level of expression of these genes in peripheral blood mononuclear cells may indicate metabolic status.

Association Between Two Common Polymorphisms of Vitamin D Binding Protein and the Risk of Coronary Artery Disease: A Case-control Study.

BACKGROUND: Coronary Artery Disease (CAD) is one of the most widespread non-communicable diseases. Vitamin Dbinding protein (VDBP) and its genetic poly morphisms have been highlighted as the susceptible components for CAD. The aim of the present study was to examine the association of VDBP single nucleotide poly morphisms (SNPs) - rs7041 and rs4588 - with CAD susceptibility among the Iranian population. METHODS: A total of 143 men with CAD and 145 healthy age-sex matched controls underwent genotyping for the - rs7041 and rs4588 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Serum level of 25(OH)D was assayed using microplate colorimetric enzyme immunoassay. RESULTS: We found a significant association between GG genotype (rs7041) and CAD (p=0.02, OR=0.537 95% CI =0.306-0.944). Regarding rs4588 polymorphism, a significant difference was observed in which the CA genotype (p=0.00032, OR=2.578, 95% CI=1.579-4.208) and allele A (P=0.028, OR=1.491, 95% CI=1.043-2.132) were significantly higher in CAD patients compared to controls. In spite of lower serum levels of 25(OH)D in CAD patients, we found no significant association between these SNPs and Vitamin D serum concentrations. CONCLUSION: We concluded that VDBP polymorphisms affect the susceptibility to CAD in Iranian men. Therefore, further studies are required to clarify the association of VDBP phenotypes and its serum levels with CAD.

Effects of Resveratrol on Crosstalk between Canonical Β-Catenin/Wnt and FOXO Pathways in Coronary Artery Disease Patients with Metabolic Syndrome: A Case Control Study.

Coronary artery disease (CAD) is the major cause of mortality and morbidity worldwide. The aim of this study was to explore the effect of resveratrol (RES) on Canonical ß-catenin/Wnt and forkhead box O (FOXO) pathways in CAD patients. We performed this study on 10 metabolic syndrome patients with three-vessel CAD and 10 sex-aged matched healthy subjects. The effects of RES on ß-Catenin, manganese superoxide dismutase (MnSOD), and peroxisome proliferator-activated receptor delta (PPAR-δ) expression were evaluated in peripheral blood mononuclear cells (PBMCs) of participants. RES could increase the MnSOD expression in CAD patients (38%, p < 0.0001). After RES treatment, the MnSOD expression of patients is still non-significantly lower than controls. In both blank and RES treatments, a significant positive correlation between ß-catenin and MnSOD mRNA expressions was found in controls, whereas no correlation between these gene expressions was found in untreated PBMCs of CAD patients. However, RES could modestly improve this pathway in CAD. RES could increase the MnSOD activity in healthy and CAD subjects (p = 0.051 and p = 0.009, respectively). Furthermore, in both blank and RES treatments, the significant correlation was found between total ß-catenin protein and the MnSOD activity in PBMCs of the controls but not in patients. The cross-talk between ß-catenin/Wnt and FOXO pathways was impaired in PBMCs of CAD patients. RES treatment could lead to a modest increase in the MnSOD activity independent of ß-catenin/FOXO pathway. Despite a modest improvement in the ß-catenin/FOXO pathway after RES treatment, this pathway was not completely repaired in CAD patients.

The association between bone turnover markers and microvascular complications of type 2 diabetes.

BACKGROUND: Global epidemic of diabetes is a serious health care concern because of its complications and consequently reduced life expectancy and increased morbidity. However, the bone turnover and thus bone health may be affected or even compromised by diabetes and its complications. The aim of this study was to assess whether bone turnover markers are associated with diabetes micro-vascular complications. METHODS: A total of 204 type 2 diabetes patients (104 patients with diabetic micro-vascular complications (retinopathy and/or nephropathy) as a case group and 100 patients without retinopathy and/or nephropathy) as a control group were recruited in this case-control study. The biochemical and metabolic parameters and bone turnover markers were assessed in all patients. RESULTS: Our findings showed serum levels of osteocalcin (OC) (p = 0.0001) and, carboxy-terminal collagen crosslinks (CTX) (p = 0.006) were higher in diabetic patients with both diabetic retinopathy and nephropathy compared with control group. However, there was no significant difference in serum levels of procollagen I aminoterminal propeptide (P1NP) between diabetic patients with diabetic retinopathy (DR) and/or diabetic nephropathy (DN) compared with control. In diabetes patients with complications, there were significant negative correlation between OC and CTX with estimated-glomerular filtration rate (e-GFR) and also positive correlation between each bone marker (OC and CTX) and PTH levels (p = 0.0001) and BUN (p = 0.0001). In a general linear model, after adjusting for age, sex and BMI, and microvascular complications, there was not any significant association between three bone turnover markers and metabolic markers including fasting glucose, insulin, and lipid profile. Among kidney markers, there were significant positive associations between serum levels of CTX and OC with BUN (p < 0.05) as well as PTH (p < 0.0001). CONCLUSIONS: Our data suggest the possible role of PTH and BUN levels in modulating bone turnover markers in diabetic patients.

Vitamin D deficiency, bone turnover markers and causative factors among adolescents: a cross-sectional study.

BACKGROUND: This cross-sectional population-based study was conducted to elucidate the prevalence of vitamin D deficiency, bone turnover marker's variation and its influencing factors among adolescents of Tehran. METHODS: Totally 444 middle and high school (53.6 % in high school) students (both girls and boys) were recruited. A short food frequency questionnaire designed to estimate dietary calcium and vitamin D consumption. Serum levels of calcium, phosphorus, parathyroid hormone (PTH), bone specific alkaline phosphates, 25 (OH) vitamin D, osteocalcin, cross-linked C-telopeptide (CTX), total protein, albumin and creatinine were determined. RESULTS: Vitamin D deficiency was prevalent in adolescents and only 22.4 % of students had normal serum vitamin D. Results revealed that vitamin D insufficiency reported in 34.2 % of students and vitamin D deficiency was in 43.3 % of them. Serum vitamin D, osteocalcin, CTX and bone specific alkaline phosphates were significantly higher in boys in all different ages. Serum levels of 25 (OH) vitamin D had positive influences on bone turnover markers and had negative correlation with PTH. CONCLUSIONS: Vitamin D deficiency and insufficiency is common among healthy adolescents of Tehran. There is a pressing need to improve vitamin D status among adolescents. Increasing vitamin D fortification of dairy products can be considered as a population-wide public health strategy in Iran.

Modulatory Role of Omentin-1 in Inflammation: Cytokines and Dietary Intake.

PURPOSE: Obesity is known as a chronic inflammatory state whereby anti-inflammatory adipokines, such as omentin-1 levels, are decreased. The present study aims to determine omentin-1 levels in relation to dietary intake, inflammation, and immune response in healthy obese individuals. METHOD: A total of 170 obese participants (body mass index [BMI] ≥ 30) were recruited in this cross-sectional study. Body composition was evaluated by a body composition analyzer, and inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin (IL)-4, IL-6, IL-1ß, IL-17, IL-10, IL-13, and tumor necrosis factor-alpha [TNF-α]) were measured by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: We observed associations between higher serum levels of omentin-1 and lower levels of fasting insulin, glucose, total cholesterol, IL-6, and TNF-α concentrations; higher levels of IL-13, IL-4, and IL-1ß were associated with higher serum levels of omentin-1 (all p < 0.05). Omentin-1 levels were not associated with IL-10, hs-CRP, and IL-17 concentrations. We also observed associations between higher intake of saturated fatty acid (SFA) and omentin-1 levels, even after adjustment for total energy intake (p = 0.04). Women with low intake of SFA had higher levels of omentin-1 (p = 0.03); a similar relation was not observed in men. CONCLUSION: Omentin-1 has an anti-inflammatory role in obesity and exerts its effects probably by inducing an increase in Th-2 cytokines comprising IL-13 and IL-4. Omentin-1 is not related to IL-17, a regulatory T cell cytokine, which modulates T helper balance. Levels of inflammatory cytokines are decreased in higher concentrations of omentin-1, except IL-1ß. Lower intake of SFA may modify omentin-1 levels in women. Our study demonstrated the probable protective role of omentin-1 in obesity-related inflammation and insulin resistance.

Transcriptomic Profiling of Extracellular RNAs Present in Cerebrospinal Fluid Identifies Differentially Expressed Transcripts in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a debilitating neurological disorder for which prognostic and diagnostic biomarkers are lacking. Cerebrospinal fluid (CSF) is an accessible body fluid that comes into direct contact with the central nervous system (CNS) and acts as a nuclease-free repository where RNA transcripts shed by brain tissues can reside for extended periods of time. OBJECTIVE: We studied the RNA species present in the CSF of PD patients to identify novel diagnostic biomarkers. METHODS: Small volumes of CSF from 27 PD patients and 30 healthy age- and sex-matched controls were used for RNA extraction followed by next-generation sequencing (RNA-seq) using the Illumina platform. CSF contains a number of fragmented RNA species that were individually sequenced and analyzed. Comparing PD to control subjects, we observed a pool of dysregulated sequencing tags that were further analyzed and validated by quantitative real-time PCR (qRT-PCR). RESULTS: A total of 201 differentially expressed sequencing tags (DETs), including 92 up-regulated and 109 down-regulated DETs were identified. We validated the following DETs by real time PCR in the patient samples: Dnmt1, Ezh2, CCR3, SSTR5,PTPRC, UBC, NDUFV2, BMP7, SCN9, SCN9 antisense (AC010127.3), and long noncoding RNAs AC079630 and UC001lva.4 (close to the LRRK2 gene locus), as potential PD biomarkers. CONCLUSIONS: The CSF is a unique environment that contains many species of RNA. Our work demonstrates that CSF can potentially be used to identify biomarkers for the detection and tracking of disease progression and evaluation of therapeutic outcomes.

Can Melatonin Act as an Antioxidant in Hydrogen Peroxide-Induced Oxidative Stress Model in Human Peripheral Blood Mononuclear Cells?

Purpose. We aimed to investigate the possible effects of melatonin on gene expressions and activities of MnSOD and catalase under conditions of oxidative stress induced by hydrogen peroxide (H2O2) in peripheral blood mononuclear cells (PBMCs). Materials and Methods. PBMCs were isolated from healthy subjects and treated as follows: (1) control (only with 0.1% DMSO for 12 h); (2) melatonin (1 mM) for 12 h; (3) H2O2 (250 µM) for 2 h; (4) H2O2 (250 µM) for 2 h following 10 h pretreatment with melatonin (1 mM). The gene expression was evaluated by real-time PCR. MnSOD and catalase activities in PBMCs were determined by colorimetric assays. Results. Pretreatment of PBMCs with melatonin significantly augmented expression and activity of MnSOD which were diminished by H2O2. Melatonin treatment of PBMCs caused a significant upregulation of catalase by almost 2-fold in comparison with untreated cells. However, activity and expression of catalase increased by 1.5-fold in PBMCs under H2O2-induced oxidative stress compared with untreated cell. Moreover, pretreatment of PBMCs with melatonin resulted in a significant 1.8-fold increase in catalase expression compared to PBMCs treated only with H2O2. Conclusion. It seems that melatonin could prevent from undesirable impacts of H2O2-induced oxidative stress on MnSOD downregulation. Moreover, melatonin could promote inductive effect of H2O2 on catalase mRNA expression.

Mediatory effect of circulating vaspin on resting metabolic rate in obese individuals.

BACKGROUND/OBJECTIVE: Vaspin is a recently identified adipokine related to obesity and insulin sensitivity. The precise mechanism of vaspin in the body is not well known, and its function in resting metabolic rate (RMR) is even less understood. Therefore, the main aim of this study was to investigate the effect of circulating vaspin on RMR in obese people. MATERIALS AND METHODS: A total of 222 obese participants were included in the current comparative cross-sectional study. Body composition was measured using body composition analyzer. RMR was measured by means of indirect calorimetry. For the measurement of vaspin serum concentrations, an enzyme-linked immunosorbent assay was used. Dietary intake was assessed using 3-day 24-h dietary recall. RESULTS: Between low and high circulating vaspin groups, there was significant difference for sex (P = 0.03), fat percent (P = 0.008), RMR per weight (P < 0.001), and RMR per fat free mass (FFM) (P = 0.007). However, there was no statistical difference between the groups in dietary intake after adjustment for energy intake (P > 0.05). Furthermore, individuals with higher level of RMR had higher vaspin concentration. Weight, visceral fat, FFM, and fat mass had significant effect on increasing RMR (P < 0.05) but after adding vaspin as a covariate in the general linear model; visceral fat (P = 0.078) and fat mass (P = 0.339) missed their effectiveness. CONCLUSION: Circulating vaspin level is higher in women than in men in obese individuals. Moreover, it was found that vaspin had mediator effect between visceral fat and fat mass associations with RMR in obese participants.

Evidence for possible role of melatonin in reducing oxidative stress in multiple sclerosis through its effect on SIRT1 and antioxidant enzymes.

AIMS: Oxidative stress plays a crucial role in the pathogenesis of multiple sclerosis (MS). Melatonin has a central role in the modulation of oxidative stress pathways. We aimed to investigate the effect of melatonin on mRNA expression and activity of sirtuin1 (SIRT1) and its target genes, manganese superoxide dismutase (MnSOD), and catalase in peripheral blood mononuclear cells (PBMCs) from MS patients and healthy subjects. KEY METHODS: This study was performed on 12 patients with relapsing-remitting MS (RRMS) and 14 age- and sex-matched healthy subjects. PBMCs were isolated and treated with pharmacological concentration of melatonin (1mM) for 12h. Gene expression was evaluated by real time-PCR. SIRT1 activity in PBMCs was measured using a fluorometric assay. MnSOD and catalase activities in PBMCs were determined by colorimetric assays. Plasma total antioxidant capacity was measured using the ferric reducing ability of plasma assay. KEY FINDINGS: Melatonin significantly increased activities and mRNA levels of SIRT1 and catalase in both patients and healthy subjects, whereas melatonin treatment caused a pronounced increase in MnSOD mRNA expression and activity only in patients. In MS patients, SIRT1 activity did not correlate with catalase and MnSOD activities before melatonin treatment, while a significant correlation was observed between SIRT1 activity and catalase activity in PBMCs of patients after melatonin treatment. SIGNIFICANCE: It appears that the antioxidant status is affected in PBMCs from MS patients and melatonin could improve impaired antioxidant defense in MS through upregulation of SIRT1, MnSOD and catalase, which might be important in MS management.