Influence of circulating nesfatin-1, GSH and SOD on insulin secretion in the development of T2DM.

Aims: To evaluate the correlation of nesfatin-1, GSH and SOD levels with ß-cell insulin secretion and their influence on insulin secretion in the development of type 2 diabetes mellitus (T2DM). Materials and methods: 75 patients with T2DM, 67 with prediabetes and 37 heathy participants were recruited in this study. Serum levels of nesfatin-1, GSH and SOD were quantified and statistically analyzed. Results: The levels of nesfatin-1, GSH and SOD in T2DM were significantly decreased (P < 0.001) compared to either in prediabetes or in healthy control, and significant reduction of these biomarkers was also observed in prediabetes when compared to the control (P < 0.001). Circulating nesfatin-1, GSH and SOD were not only strongly correlated with ß-cell insulin secretion, but also exerted remarkable influence on the secretion. Conclusion: Serum nesfatin-1, GSH and SOD are important factors involving insulin secretion in the development of T2DM, which may help provide new ideas for forthcoming investigations on the roles of these factors in pathogenesis of T2DM, as well as for active prediction and prevention of prediabetes before it develops into overt T2DM.

BMP-4 impedes endothelial cell migration in neointimal hyperplasia via FoXO-3 specific modulation of reactive oxygen species.

BACKGROUND AND AIMS: Endothelial cell injury causes vascular barrier dysfunction and leukocyte recruitment to the underlying tissue. Bone morphogenetic protein 4 (BMP-4) is a transforming growth factor that exerts pro-inflammatory effects on the endothelium. Here, we investigated the effects of BMP-4 on endothelial cell (EC) migration following balloon injury in SD rats. METHODS: An intimal hyperplasia model was established using balloon injury. Hematoxylin-eosin staining (HE) and silver staining were used to detect the alteration of endothelial cells recovery after balloon injury. Serum BMP-4 levels were assessed by ELISA. Human umbilical vein endothelial cells (HUVECs) were cultured. MTT assay was used to measure cell viability. Protein expression was detected by Western blot. Intracellular reactive oxygen species (ROS) was detected by dichloro-dihydro-fluorescein diacetate (DCFH-DA). HUVECs migration was measured via transwell assay and scratch wound assay. RESULTS: The results indicated that BMP-4 inhibition significantly decreased total plasma activity of BMP-4 and reduced neointimal hyperplasia by stimulating endothelial cell migration, but did not affect the medial area following balloon injury. BMP-4 suppressed the formation of ROS via forkhead box O3 (FoXO-3)/superoxide dismutase 1 (SOD-1). In vitro, a high level of ROS induced by BMP-4 impeded HUVECs migration. CONCLUSIONS: The results suggest that BMP-4 inhibition is a potential means of preventing intimal hyperplasia formation after balloon injury.

Age- and sex-specific reference intervals for superoxide dismutase enzyme and several minerals in a healthy adult cohort.

INTRODUCTION: The aim of this study was to establish RIs for clinically important markers including superoxide dismutase (SOD), serum copper, zinc, calcium, magnesium, and phosphate in a cohort of healthy Iranian adults. MATERIALS: A subsample from MASHAD cohort study was used to assess serum SOD, copper, zinc, calcium, magnesium and phosphate. Serum SOD was measured according to its inhibitory potential of pyrogallol oxidation. Micro- and macro-minerals were measured using flame atomic absorption spectrometry and a BT3000 autoanalyzer, respectively. Sex- and age-specific RIs were then calculated based on CLSI Ep28-A3 guidelines. RESULTS: Reference value distributions for studied parameters did not demonstrate any age-specific differences that were statistically significant. In addition, sex partitioning was not required for all parameters, apart from serum magnesium, which showed a wider range in females (0.81-1.26 mg/dl) compared with males (0.82-1.23 mg/dl). CONCLUSION: The RIs established in this study can be expected to improve mineral assessment and clinical decision-making in the Iranian adult population.

FGF23, a novel muscle biomarker detected in the early stages of ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.

The rs2234694 and 50 bp Insertion/Deletion polymorphisms of the SOD1 gene are associated with breast cancer risk in a Mexican population.

OBJECTIVE: The rs2234694 and 50 bp insertion/deletion (Ins/Del) polymorphisms of the SOD1 gene have been shown to be associated with many diseases, but in breast cancer (BC) their association has not been detected. The purpose of this study was to determine the frequency and association of SOD1 gene polymorphisms (rs2234694 and 50 bp Ins/Del) in BC patients in the Mexican population. MATERIALS AND METHODS: The SOD1 polymorphisms were determined by Polymerase Chain Reaction (PCR) in Mexican healthy subjects and BC patients. RESULTS: The rs2234694 polymorphism was associated with BC susceptibility when BC patients and the control group were compared for the AC genotype (p<0.0001), the AC/CC genotype (dominant model: p<0.0001), and the C allele (p<0.0001). The 50 bp Ins/Del polymorphism was associated with BC susceptibility for the Del allele (p=0.048), although the association between the dominant model AC/CC (rs2234694) and BC patients was evident for menopause [adjusted odds ratio (OR) 1.65 (95% CI 1.05-2.7); p=0.048], Ki-67 (≥15%) (OR1.9, 95% CI 1.14- 3.16, p=0.016), and the presence of DM2 (OR 2.4, 95% CI 1.35- 4.31, p=0.003). A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for estrogen receptor (ER) and progesterone receptor (PR), carrying the AC genotypes (OR 0.47, 95% CI 0.23-0.94, p= 0.033) and CC (OR 0.11, 95% CI 0.013-1.07, p=0.047). The association between the InsDel/DelDel (dominant model; 50 bp Ins/Del) genotype and BC with metastatic lymph nodes (OR 1.5, 95% CI 1.1-2.25, p=0.019), hematologic toxicity (OR 1.5, 95%CI 1.1-2.23, p=0.015), gastric toxicity (OR 1.5, 95%CI 1.1-2.07, p=0.030), and Ki-67 (≥15%) (OR1.6, 95%CI 1.2-2.26, p=0.002) was evident, indicating that these factors may contribute significantly to BC risk. The C/Ins haplotype was also associated with BC susceptibility (OR3.47, 95% CI 1.62-7.74, p=0.001). CONCLUSIONS: rs2234694 and 50 bp Ins/Del polymorphisms in the SOD1 gene were associated with BC susceptibility in a Mexican population. A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for ER and PR, carrying the AC genotypes. The haplogenotypes AA/InsIns and AC/InsDel could contribute significantly to BC risk in gastric and hematologic toxicities, metastatic lymph nodes, and the presence of DM2 in the Mexican population analyzed.

Alterations in Concentration/Activity of Superoxide Dismutases in Context of Obesity and Selected Single Nucleotide Polymorphisms in Genes: SOD1, SOD2, SOD3.

Little is known about the contribution of each of the three superoxide dismutase isozymes (SODs) to the total SOD activity in extracellular fluids. This study was aimed to investigate the alterations in concentration/activity of (SODs) in plasma, in context of sex, obesity, exposition to cigarette smoke, and genotypic variability of five selected single nucleotide polymorphisms (SNPs) in genes SOD1, SOD2, SOD3. Men showed higher SOD1 concentration, lower SOD3 concentration and higher total antioxidative capacity (TAC) values. Intersexual variability was observed in concentration of copper, zinc, and cadmium. The obese showed higher total oxidative capacity regardless of sex. An increase in SOD2 activity was coexistent with obesity in men, and exposition to cigarette smoke in non-obese individuals. Additionally, in state of this exposition, Cu,Zn-SOD contribution to the total SOD was lower. Interestingly, over 90% of the obese were of C/T genotype of rs4880 (SOD2). Non-obese of T/T genotype (rs4880) were of lower total SOD activity due to decrease in both Cu,Zn-SOD and Mn-SOD activities. SNP rs2234694 was associated with differences in concentration of SODs, depending on obesity status. Correlations indicate that both TAC and SODs, together, may adapt to insulin resistance and inflammation-derived oxidative stress found in obesity. This topic should be further investigated.

Antioxidant status and cytogenetic damage in hospital workers occupationally exposed to low dose ionizing radiation.

The aim of the present study was to assess the oxidative stress level and chromosomal damage induced by occupational exposure to low dose ionizing radiation (LDIR). Two hundred and eighteen hospital workers occupationally exposed to LDIR were included in this study, along with 118 healthy age- and gender-comparable controls. Occupational dosimetry records were collected over the last year and revealed that the accumulated annual dose for each hospital worker was below the permissible limit of the International Commission on Radiological Protection (ICRP). The individuals' oxidative and antioxidative status were determined by measuring the activities of copper zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), catalase (CAT) enzymes, and the levels of malondialdehyde (MDA) in erythrocytes. The effect of radiation on chromosomal integrity was measured by the frequency of micronuclei (MN) formation using the cytokinesis block technique. Our results showed that the activities of CuZn-SOD and CAT enzymes and MDA levels observed in the hospital workers were higher than those in the controls (p < 0.05). We did not find significant difference in GSH-Px enzyme activity between the two groups (p = 0.247). A higher frequency of MN was found in exposed groups than in the controls [3(1-5) ‰ versus 2(0.75-4) ‰; p<0.001]. The difference was significant for males (p = 0.012), but not females (p = 0.14). Multiple linear regression analysis showed differences in the oxidant activities and MN frequency between hospital workers and controls adjusted for age, gender, smoking status and drinking status. Correlation analysis indicated that the frequency of MN was positively associated with MDA levels (p < 0.05). Altogether, these results support the detrimental effects of chronic low dose radiation in humans, which involves the induction of oxidative stress and chromosomal damage.

The Evaluation of the Antioxidant and Intestinal Protective Effects of Baicalin-Copper in Deoxynivalenol-Challenged Piglets.

The present study was performed to evaluate the antioxidant and intestinal protective effects of baicalin-copper on deoxynivalenol-challenged piglets. Forty weaned piglets were randomly divided into four groups and assigned to different diets: (1) basal diet (Con), (2) 4 mg/kg deoxynivalenol of basal diet (DON), (3) 5 g/kg baicalin-copper of basal diet (BCU); and (4) 4 mg/kg deoxynivalenol + 5 g/kg baicalin-copper of basal diet (DBCU). The results showed that the ADFI and ADG of piglets in the DON group were markedly lower than those in the Con group, but the ADFI and ADG of the DBCU group were not significantly different from those of the Con group. In piglets fed a DON-contaminated diet, dietary supplementation with BCU significantly decreased the mRNA levels of P70S6K, 4E-BP1, and HSP70 in the liver, the protein expression of HO-1 in the jejunum, and the expression of p-Nrf2 and p-NF-κB in the ileum but increased Mn-SOD activity in serum. Dietary supplementation with BCU increased jejunal maltase, ZIP4 and MT mRNA levels, and serum concentrations of Arg, Val, Ile, Leu, Lys, and Tyr in DON-contaminated piglets. In summary, BCU can alleviate the growth impairment induced by DON and enhance antioxidant capacity and nutrition absorption in piglets fed DON-contaminated diets.

The Effects of Synbiotic Supplementation on Antioxidant Capacity and Arm Volumes in Survivors of Breast Cancer-Related Lymphedema.

Background and Aims: Synbiotics found to be beneficial in breast cancer survivors (BCSs) through its antioxidant properties. The aim of this study was to assess the effects of synbiotic supplementation on edema volume and some oxidative markers among obese and overweight patients with BCRL.Method: This randomized double-blind, placebo-controlled trial was conducted on 88 overweight and obese BCSs aged 18-65 years. All the subjects were given a specified low-calorie diet (LCD) and were randomly assigned into two groups to intake 109 CFU/day synbiotic supplement (n = 44) or placebo (n = 44) for 10 wk. Edema volume and serum total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) concentration were measured at baseline and after the 10-wk intervention.Results: Ten-wk supplementation with synbiotics leads to a significant reduction in serum MDA levels (P = 0.001) and an increase in serum SOD concentration (P = 0.007) compared to placebo. No significant changes were observed in serum GPx, TAC, and edema volume between groups.Conclusion: Our findings reveal that 10-wk synbiotic supplementation along with a LCD program-reduced serum MDA levels and elevate the activity of SOD in overweight and obese patients with BCRL. However, its effect on serum GPx, TAC, and edema volume was not significant.

Antioxidant enzymes expression in lymphocytes of patients undergoing carotid endarterectomy.

To remedy carotid artery stenosis and prevent stroke surgical intervention is commonly used, and the gold standard being carotid endarterectomy (CEA). During CEA cerebrovascular hemoglobin oxygen saturation decreases and when this decrease reaches critical levels it leads to cerebral hypoxia that causes neuronal damage. One of the proposed mechanism that affects changes during CEA and contribute to acute brain ischemia (ABI) is oxidative stress. The increased production of reactive oxygen species and reactive nitrogen species during ABI may cause an unregulated inflammatory response and further lead to structural and functional injury of neurons. Antioxidant activity are involved in the protection against neuronal damage after cerebral ischemia. We hypothesized that neuronal injury and poor outcomes in patients undergoing CEA may be results of oxidative stress that disturbed function of antioxidant enzymes and contributed to the DNA damage in lymphocytes.

Effects of postprandial hydroxytyrosol and derivates on oxidation of LDL, cardiometabolic state and gene expression: a nutrigenomic approach for cardiovascular prevention.

BACKGROUND AND AIM: Cardiovascular diseases (CVDs) are the most frequent causes of death in the world. Inflammation and oxidative damage contribute significantly to the development of atherosclerosis and CVDs. European Food Safety Authority scientific opinion has acknowledged that hydroxytyrosol (3,4-dihydroxyphenylethanol) and derivatives, contained in extra virgin olive oil (EVOO), typically used in Mediterranean diet may play a crucial role in the reduction of the inflammatory pathway and in the prevention of CVDs. The aim of the study was to determine the effect in healthy volunteers of 25 g of phenols-rich EVOO (p-EVOO). METHODS: The clinical study was a randomized, controlled trial to determine the acute effect in the postprandial time of 25 g of p-EVOO. We evaluated nutritional status using anthropometric parameters, body composition, serum metabolites, oxidative stress biomarkers and gene expression of eight genes related to oxidative stress and human inflammasome pathways, lasting 2 h after p-EVOO administration. Twenty-two participants resulted as eligible for the study. RESULTS: A significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index was highlighted (P < 0.05). Significant upregulation of catalase, superoxide dismutase 1 and upstream transcription factor 1 were observed (P < 0.05). CONCLUSION: The current study shows that intake of 25 g of p-EVOO has been able to be modulated, in the postprandial time, the antioxidant profile and the expression of inflammation and oxidative stress-related genes, as superoxide dismutase 1, upstream transcription factor 1 and catalase. We also observed a significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index. We have demonstrated that a daily intake of phenols and antioxidants can reduce the inflammatory pathway and oxidative stress and therefore the risk of atherosclerosis and CVDs. More studies on a larger population are necessary before definitive conclusions can be drawn.Trial registration ClinicalTrials.gov NCT01890070.

Effects of chia (Salvia hispanica L.) on oxidative stress and inflammation in ovariectomized adult female Wistar rats.

The present study investigated the influence of chia consumption on inflammation, oxidative stress, and lipid profiles in adult female ovariectomized rats fed a high-fat diet. Forty ovariectomized and 40 intact (SHAM) rats were allocated into 8 groups (n = 10), and each rat received one of the following four diets: standard diet (ST); standard diet + chia (STC); high-fat diet (HF); and high-fat diet + chia (HFC) for 126 days. Biochemical parameters and biomarkers of lipid peroxidation, inflammation, and oxidative stress were evaluated. The mRNA expression levels of PPAR-α, NFκB, TNF-α and Zn-SOD1 were analyzed, as well as those of TNF-α and IL-1ß. Chia intake increased HDL cholesterol (HDL-c) and reduced LDL cholesterol (LDL-c) levels. Plasma catalase activity was elevated in the STC group. Concentrations of TBARS were higher in all groups fed HF. PPAR-α mRNA expression was elevated, and levels of NFκB mRNA expression were reduced in the STC group. mRNA expression and protein levels of TNF-α were lower in rats fed the standard diet. Protein levels of IL-1ß were reduced in rats fed the standard diet, and the high fat diet with chia. In general, ovariectomy did not influence the inflammatory and oxidative stress parameters. Chia intake improved antioxidant activity by increasing SOD expression, PPAR-α expression, catalase activity, and HDL-c levels. In addition, chia consumption decreased the concentrations of the inflammatory markers IL-1ß and LDL-c.

Evaluation and Monitoring of Superoxide Dismutase (SOD) Activity and its Clinical Significance in Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND This systematic review of the literature and meta-analysis aimed to review the evaluation and monitoring of superoxide dismutase (SOD) activity and its clinical significance in gastric cancer. MATERIAL AND METHODS Systematic review involved searching the PubMed, Embase, Ovid, and the China National Knowledge Infrastructure (CNKI) databases. Search terms included 'superoxide dismutase,' and 'gastric cancer.' Studies that included measurements of SOD activity in peripheral blood samples in patients with SOD activity compared with healthy controls. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS Ten controlled clinical studies were identified that included six studies that measured SOD in serum, three in erythrocytes, and one study that measured SOD on whole blood. Meta-analysis, using the standardized mean difference (SMD) and the 95% confidence interval (CI), showed that patients with gastric cancer had significantly decreased SOD activity when compared with the healthy controls (SMD, -0.840; 95% CI, -1.463 to -0.218; p=0.008). Subgroup analysis was conducted on SOD distribution in the blood (erythrocyte: SMD, -1.773; 95% CI, -2.504 to -1.042; p=0.000) (serum SMD, -0.322; 95% CI, -1.006-0.361; p=0.355) (whole blood: SMD, -1.251; 95% CI, -1.731 to -0.771; p=0.000) and for male subjects (SMD, -2.090; 95% CI, -2.725 to -1.456; p<0.001). CONCLUSIONS Meta-analysis showed that SOD measurements from blood samples, especially in erythrocytes, had potential as a diagnostic and monitoring parameter in patients with gastric cancer.

Effects of chia (Salvia hispanica L.) on calcium bioavailability and inflammation in Wistar rats.

Chia is a good source of calcium, however it is not been previously reported its bioavailability associated with an inflammatory condition. Thus, the present study evaluated the effect of chia on calcium bioavailability, inflammation, and oxidative stress in Wistar rats fed a high-fat diet or standard diet for 35 days. Chia consumption resulted in lower calcium balance and calcium absorption and retention rates. In addition, the urinary calcium concentration was lower in groups that were fed chia. The bone resistance of animals feed chia was lower than that in rats fed the standard diet receiving calcium carbonate. Animals that were fed chia showed lower total, very low-density lipoprotein, and low-density lipoprotein cholesterol levels than animalsfed calcium carbonate. Animals fed standard diet showed higher superoxide dismutase plasma concentrations than animals in the high fat calcium carbonate group. PPAR-α protein levels were higher in animals fed chia whereas TNF-α and IL-10 were lower in these animals. NFκB mRNA expression and protein levels were lower in the groups that received chia compared with HFD + CC. Chia intake presented low calcium bioavailability regardless of the type of diet consumed and was able to improved inflammation and the lipid profile in young Wistar rat. Besides this, the consumption of this seed increased the activity of antioxidants enzymes.

The impact of antihypertensive pharmacotherapy on interplay between protein-bound uremic toxin (indoxyl sulfate) and markers of inflammation in patients with chronic kidney disease.

PURPOSE: Indoxyl sulfate (IS) is one of the most potent uremic toxins involved in chronic kidney disease (CKD) progression, induction of inflammation, oxidative stress, and cardiovascular diseases occurrence. It is proved that hypertension is a common CVD complication and a major death risk factor as well as contributes for decline in a renal function. The aim of our study was to investigate how implementing of antihypertensive therapy impact IS concentrations and the associations between IS and markers of renal function, inflammation and oxidative stress. METHODS: Study was conducted on 50 patients diagnosed with CKD and hypertension, divided into three groups: without hypotensive therapy (CKD-NONE), hypotensive monotherapy (CKD-MONO), and hypotensive polypharmacotherapy (CKD-POLI), and 18 healthy volunteers. The markers of inflammation [interleukin-6, tumor necrosis factor-alpha (TNF-α), high-sensitive C-reactive protein (hs-CRP), neopterin, ferritin], oxidative status [superoxide dismutase (Cu/Zn-SOD), antibodies against oxidized low-density lipoprotein (oxLDL-abs)], and selectins were determinate using immunoenzymatic methods. IS levels were assayed using high-performance liquid chromatography and other parameters were analysed using routine laboratory techniques. Then cross-sectional analysis was performed. RESULTS: Elevated levels of IS, indicators of kidney function, markers of inflammation and blood pressure values were observed in each CKD subgroups. There was no effect of antihypertensive therapy on IS levels between studied groups, as well as there was no clear relationship between IS and blood pressure values in each studied group. The positive associations between IS and Cu/Zn SOD, neopterin, hs-CRP, creatinine and neutrophils/lymphocytes ratio were observed in CKD-NONE and CKD-POLI subgroups. Additionally, in CKD-POLI group IS positively correlated with TNF-α, ferritin and neutrophils. In CKD-MONO group, IS was positively related to oxLDL-abs, neopterin, E-selectin and creatinine, whereas it was inversely associated with hs-CRP. CONCLUSIONS: Our study showed for the first time that the antihypertensive therapy has no impact on IS levels in CKD patients with hypertension. However, the introduction of the antihypertensive therapy modified the dependencies between IS and the studied markers of kidney function, inflammation, oxidative stress and hematological parameters that are crucial for mortality and morbidity amongst the CKD patients with hypertension.

Oxidative stress and inflammation, two features associated with a high percentage body fat, and that may lead to diabetes mellitus and metabolic syndrome.

Obesity is an important feature of the metabolic syndrome and is associated with an increased risk of type 2 diabetes mellitus, cardiovascular disease, and some cancers. The aim of this study was to determine the relationship between body fat percentage and an imbalance of the prooxidant/antioxidant balance (PAB), serum superoxide dismutase (SOD1) and inflammation (serum hs-CRP) and increase risk of metabolic syndrome and diabetes mellitus. In this study, 9154 individuals were recruited as part of the Mashhad Stroke and Heart Association Disorder (MASHAD) study. Subjects were categorized into two groups according to body fat percentage as defined >25% in male and > 30% in female, according to gender. Biochemical factors, including serum PAB, SOD1, and hs-CRP were measured in all subjects. SPSS version 18 was used for statistical analyses for all. GraphPad Prism 6 for figures was used. Of total number of subjects (9154), 6748 (73.7%) were found to have a high body fat (BF) percentage. Serum hs-CRP and PAB were significantly higher in individuals with a high BF percentage (P < 0.05) but SOD1 was not significantly different between the two groups (P > 0.05). BF percentage, serum PAB and serum hs-CRP were significantly higher in individuals with metabolic syndrome and diabetes versus those without metabolic syndrome and diabetes mellitus (P < 0.05), however serum SOD1 was significantly lower in individuals with metabolic syndrome (P < 0.005). Oxidative stress and inflammation are two factors that may link the presence of high BF percentage with the development of metabolic syndrome, diabetes, and cardiovascular disease. © 2018 BioFactors, 45(1):35-42, 2019.

Increased IL-1ß levels are associated with an imbalance of "oxidant/antioxidant" status during Behçet's disease.

Behçet's disease is a multisystem disease. It stands at the crossroad between the autoimmunity and auto-inflammatory disorders. In this study, we sought to address a relationship that might exist between interleukin-1ß (IL-1ß) and the oxidants/antioxidants markers in Behçet's patients. Behçet's disease patients (n = 78: active stage, n = 28; inactive stage, n = 50) and 41 healthy controls have been included in our study. In this context, we investigated the plasma levels of IL-1ß and the nitrosative/oxidative markers: nitric oxide (NO), advanced oxidative protein products (AOPP) and fatty acids peroxidation-malondialdehyde (MDA). The antioxidant system was assessed by measuring the plasma level of superoxide dismutase (SOD) activity. The Mann-Whitney's U and Pearson's correlation tests were used for statistical analyses. Our case-control study showed that patients in active stage displayed higher plasma levels of IL-1ß, NO, AOPP and MDA versus healthy controls and patients in inactive stage. Patients in active stage showed significantly lower SOD levels related to patients in inactive stage and healthy controls respectively, whereas patients in inactive stage showed statistically insignificant SOD level versus healthy controls. Correlation studies showed a significant positive correlation between IL-1ß and AOPP, IL-1ß and NO, and negative correlation between IL-1ß and SOD among Behçet's disease patients. In addition, we showed positive correlation between AOPP and NO, AOPP and MDA and negative correlation between NO and SOD, AOPP and SOD in Behçet's disease patients. Interestingly, our study revealed that IL-1ß levels increased and correlated with an imbalance of oxidants/antioxidants system, especially during active stage of Behçet disease. Collectively, our study indicates a possible link between IL-1ß production and nitrosative/oxidative markers during Behçet's disease. Exploiting this relationship might provide valuable outputs in the follow-up and prognosis of Behçet's disease with a potential therapeutic value.

Oxidative stress in electrohypersensitivity self­reporting patients: Results of a prospective in vivo investigation with comprehensive molecular analysis.

A total of 32 electrohypersensitivity (EHS) self­reporting patients were serially included in the present prospective study for oxidative stress and antioxidative stress response assessment. All thiobarbituric acid­reactive substances (TBARs) were measured in the plasma, particularly malondialdehyde (MDA) for lipid peroxidation; additional measurements included total thiol group molecules, reduced glutathione (GSH), oxidized glutathione (GSSG) for oxidative stress assessment and nitrotyrosine, a marker of peroxynitrite­induced oxidative/nitrosative stress. In addition, the activity of Cu­Zn superoxide dismutase (SOD1) was measured in red blood cells (RBCs) and glutathione reductase (GR) and glutathione peroxidase (GPx) in RBCs and plasma. Depending of the biomarker considered, 30­50% of EHS self­reporting patients presented statistically significantly increased TBARs, MDA, GSSG and NTT mean plasmatic level values in comparison with normal values obtained in healthy controls (P<0.0001). By contrast, there were no plasmatic level values above the upper normal limits for GSH, GSH/GSSG ratio, total glutathione (GluT) and GSH/GluT ratio, and values for these GSH­associated biomarkers were statistically significantly decreased in 20­40% of the patients (P<0.0001). Furthermore, in RBCs, mean SOD1 and GPx activities were observed to be statistically significantly increased in ~60% and 19% (P<0.0001) of the patients, respectively, while increased GR activity in RBCs was observed in only 6% of the patients. The present study reports for the first time, to the best of our knowledge, that overall ~80% of EHS self­reporting patients present with one, two or three detectable oxidative stress biomarkers in their peripheral blood, meaning that these patients­as is the case for cancer, Alzheimer's disease or other pathological conditions­present with a true objective new pathological disorder.

Gallstone Patients with Enhanced Oxidative Stress Biomarker Superoxide Dismutase (SOD1) Plasma Levels Have Significantly Lower Number of Postoperative Analgesic Oxycodone Doses: A Prospective Study with Special Reference to Cancer Patients.

BACKGROUND/AIM: Oxidative stress biomarker superoxide dismutase (SOD1) plasma levels in operated gallstone patients versus cancer patients are unknown. In addition, the number of analgesic doses during the first 24 h postoperatively (NAD24) in gallstone patients operated with laparoscopic cholecystectomy (LC) or minicholecystectomy (MC) is unreported. The aim of the study was to determine a correlation between the plasma SOD1 levels in the LC and MC patients versus cancer patients. PATIENTS AND METHODS: Initially, 114 patients with symptomatic gallstone disease were randomized into LC (n=54) or MC (n=60) groups. The plasma levels of the SOD1 marker were measured just before, immediately after (POP1) and 6 h after the operation (POP2). RESULTS: The median plasma SOD1 levels preoperatively and following surgery in the LC and MC patients versus cancer patients were statistically insignificant (p=0.90, p=0.88, p=0.21, respectively). The median plasma levels of SOD1 increased immediately after operation (POP1) and the postoperative elevation between the preoperative (PRE) and the POP1 values in the SOD1 marker were statistically significant (p=0.027). Then the median plasma levels of SOD1 marker decreased 6 h postoperatively (POP2) and the decrease between the POP1 and POP2 values in the SOD1 marker were statistically highly significant (p<0.001). There is a highly significant inverse correlation between the individual values of the NAD24 and plasma SOD1 values postoperatively in LC and MC patients (r=-0.335, p=0.011). CONCLUSION: The plasma SOD1 levels preoperatively and following surgery in the LC and MC patients versus cancer patients were quite similar. Cholecystectomy patients with enhanced levels of SOD1 appeared to have significantly lower number of analgesic oxycodone doses during the first 24 h postoperatively (NAD24).

Proteomic profiling for plasma biomarkers of tuberculosis progression.

Severe pulmonary tuberculosis (STB) is a life­threatening condition with high economic and social burden. The present study aimed to screen for distinct proteins in different stages of TB and identify biomarkers for a better understanding of TB progression and pathogenesis. Blood samples were obtained from 81 patients with STB, 80 with mild TB (MTB) and 50 healthy controls. Differentially expressed proteins were identified using liquid chromatography­tandem mass spectrometry­based label­free quantitative proteomic analysis. Functional and pathway enrichment analyses were performed for the identified proteins. The expression of potential biomarkers was further validated by western blot analysis and enzyme­linked immunosorbent assays. The accuracy, sensitivity and specificity for selected protein biomarkers in diagnosing STB were also evaluated. A total of 1,011 proteins were identified in all three groups, and 153 differentially expressed proteins were identified in patients with STB. These proteins were involved in 'cellular process', 'response to stimulus', 'apoptotic process', 'immune system process' and 'select metabolic process'. Significant differences in protein expression were detected in α­1­acid glycoprotein 2 (ORM2), interleukin­36α (IL­36α), S100 calcium binding protein A9 (S100­A9), superoxide dismutase (SOD)1 in the STB group, compared with the MTB and control groups. The combination of plasma ORM2, IL­36α, S100A9 and SOD1 levels achieved 90.00% sensitivity and 92.16% specificity to discriminate between patients with STB and MTB, and 89.66% sensitivity and 98.9% specificity to discriminate between patients with STB and healthy controls. ORM2, S100A9, IL­36α and SOD1 were associated with the development of TB, and have the potential to distinguish between different stages of TB. Differential protein expression during disease progression may improve the current understanding of STB pathogenesis.