Search

Early diagnosis of Alzheimer's disease (AD) using potential biomarkers may help with implementing early therapeutic interventions, monitoring, and ultimately disease treatment. The current study aimed to evaluate serum levels of DKK-1, TNC, and oxidative stress markers, as well as analyzing the expression of LRP6, GSK3A, and GSK3B genes in patients with AD. Serum levels of DKK-1, TNC, TOS, TAC, and MDA were measured in 40 AD patients and 40 healthy individuals. Additionally, the relative expressions of LRP6, GSK3A, and GSK3B genes in whole blood were evaluated. Receiver operating characteristic (ROC) analysis was used to investigate the incremental diagnostic value of each factor in the study groups. Mean serum levels of DKK-1, TNC, TOS, TAC, and MDA were significantly higher in the AD group compared to the healthy group (p0.001). Moreover, a significant difference was observed in the expression of LRP6 and GSK3A genes (p0.001) between patients and healthy groups. However, the expression of GSK3B did not significantly differ between the two groups (p0.05). With considerable sensitivity and specificity, ROC analysis demonstrated the diagnostic efficacy of DKK-1 and TNC serum levels in AD within an area under the ROC curve of ≥ 0.98 (p ˂ 0.001). The results showed that evaluating serum levels of DKK-1 and TNC, as well as assessing the expression of LRP6, could be utilized for diagnosis and monitoring of AD patients.

Introduction: Nephrotoxicity as a side effect caused by the immunosuppressive drug, cyclosporine-A (CsA), can be a major problem in transplant medicine. Oxidative stress may play an important role in the CsA-induced nephrotoxicity. It has been shown that the antihypertensive drug, valsartan (Val), has also renoprotective effects but, its molecular mechanism is largely unknown. In the present study, it was aimed to evaluate the Val effect in the alleviation of CsA nephrotoxicity via probable renal glutathione peroxidase (GPx) upregulation and oxidative stress decrease. Methods: Thirty-two Sprague-Dawley rats were divided into four groups based on CsA and/or Val administration: group A (Control, 1 mL/kg/day of olive oil as vehicle), group B (CsA, 30 mg/kg/day), group C (CsA+Val, 30+30 mg/kg/day), and group D (Val, 30 mg/kg/day). After the administration period (six weeks), renal GPx expression was evaluated by real-time polymerase chain reaction (PCR). Plasma levels of GPx and 8-Hydroxydeoxyguanosine (8-OHdG) were measured by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) and protein carbonyl groups (PCG) were measured by spectrophotometer. Plasma levels of urea and creatinine were measured by an autoanalyzer. Results: CsA treatment led to the decrease in renal expression and plasma levels of GPx in comparison to other study groups. Rats received CsA were detected to have significantly (p

Objective Multiple Sclerosis (MS) is a disease of the central nervous system, which ultimately may lead to various disabilities in patients. No definitive cure has yet been developed for the disease. MRI is the method of choice for imaging MS plaques, which would be useful in disease diagnosis as it becomes progressive. Therefore, this study aimed to investigate the serum levels of ANT1 (adenine nucleotide translocase 1), ATG5 (autophagy-related protein 5), and Parkin in patients with MS, all of which play essential roles in MS pathophysiology, as novel serum biomarkers for early diagnosis of the disease. Design and methods Forty patients in the early stages of the disease, and 40 healthy individuals were selected as the case and control groups. Upon sampling, the serum levels of the biomarkers were measured. Results The results indicated that autophagy, mitophagy, and mitochondrial apoptosis were different in the case and control groups. The oxidative stress level evaluation revealed low concertation of total antioxidant status (TAS) in the MS patients, while a partial increase accompanied the malondialdehyde (MDA). No significant correlation was observed between oxidative stress and autophagy or mitophagy factors. Conclusion According to the results obtained from this study, the evaluation of serum levels of ANT1, ATG5, and Parkin could be applied in the diagnosis and follow-up of MS patients.

Background: Diabetic nephropathy (DN) is characterized by albuminuria, hypertension, and a progressive decline in glomerular filtration rate. The 3-hydroxy-3-methylglutaryl coenzyme A is a well-known agent that is active in lowering total plasma and low-density lipoprotein cholesterol (LDL-C) levels in cases with hypercholesterolemia. Hence, in this study, proteinuria changes at the beginning and after the withdrawal of lovastatin in patients with type 2 DN (T2DN) were studied. Materials and Methods: Lovastatin was administered for thirty male patients with T2DN and then was withdrawn. Twenty-four hours, urine creatinine and protein levels were determined. Results: The mean levels of total cholesterol and LDL-C were reduced without any change in the triglyceride (TG) level while the high-density lipoprotein cholesterol (HDL-C) level was increased. There was a reverse linear correlation between the changes in the level of HDL-C and the changes in the level of 24 h urine protein after 90 days of lovastatin therapy (P = 0.007, r = −0.484). Conclusions: Short-term 3-month lovastatin therapy has no effect on proteinuria levels in patients with T2DN despite the antihyperlipidemic effects and reverse correlation of proteinuria with HDL-C.

Aim The present study aimed to determine the effects of Elaeagnus angustifolia L. supplement on serum antioxidant status in females with knee osteoarthritis. Methods In this 8-week randomized clinical trial, 90 females with knee osteoarthritis were randomly assigned to one of three groups—medulla powder (15 g medulla powder), whole fruit powder (15 g whole fruit powder) or placebo. Information on dietary intake was collected using 24-h recall method for 3 days (one weekend day included). The serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA) were measured using the Randox ® assay and the fluorometry method respectively. Paired sample t -test, ANOVA and ANCOVA were used for statistical analysis. Results The mean serum TAC level in the medulla, whole fruit and placebo groups increased from 1.12 ± 0.34 to 1.28 ± 0.27, 1.30 ± 0.28 to 1.50 ± 0.28 and 1.18 ± 0.19 to 1.30 ± 0.22 mmol/L respectively. In terms of the TAC level, the significant increase was only observed in the whole fruit group ( P = 0.001). The mean serum MDA level in the medulla, whole fruit and placebo groups decreased from 3.80 ± 0.33 to 3.30 ± 0.41, 3.25 ± 0.51 to 2.45 ± 0.43 and 3.38 ± 0.63 to 2.56 ± 0.41, respectively. A statistically significant reduction was observed only in the whole fruit group ( P = 0.009). Discussion Based on the results, E. angustifolia L. in the form of whole fruit had beneficial effects on serum TAC and MDA levels in females with knee OA. This may show a possible disease modifying effect of E. angustifolia L. in knee osteoarthritis.

Purpose: Oxidative stress plays a key role in the onset and development of diabetes complications. In this study, we evaluated whether voluntary exercise could alleviate oxidative stress in the heart and blood of streptozotocin - induced diabetic rats. Methods: 28 male Wistar rats were randomly divided into four groups (n=7): control, exercise, diabetes and exercise + diabetes. Diabetes was induced by injection of streptozotocin in male rats. Rats in the trained groups were subjected to voluntary running wheel exercise for 6 weeks. At the end of six weeks blood and heart tissue samples were collected and used for determination of antioxidant enzymes (including SOD, GPX and CAT activities) and MDA level. Results: Exercise significantly reduced MDA levels both in the heart tissue (p

BACKGROUND Nephrotoxicity side effect of the immunosuppressive drug, cyclosporine A (CsA), can be a major issue in transplantation medicine. Cyclosporine A-induced nephrotoxicity is multifactorial but oxidative stress has a critical role in this process. It has been demonstrated that Valsartan (Val) as an angiotensin receptor blocker has renoprotective effects, but the molecular mechanisms responsible for the renal protection, independent from its blood pressure lowering effect, have not yet been fully understood. The present study is aim at evaluating the Val effect in alleviation of CsA nephrotoxicity by probable increase in renal Klotho expression and/or reducing oxidative stress. METHODS Thirty-two Sprague-Dawley rats were divided into 4 groups based on the administration of CsA and/or Val: group A (control, 1 mL/kg per day of olive oil as vehicle), group B (CsA, 30 mg/kg per day), group C (CsA + Val, 30 + 30 mg/kg per day), and group D (Val, 30 mg/kg per day). Real-time polymerase chain reaction and Western blotting were used to evaluate Renal Klotho expression. Serum Klotho level was measured by enzyme-linked immunosorbent assay. 8-Hydroxy-deoxy guanosine and malondialdehyde levels as markers of oxidative stress were measured by enzyme-linked immunosorbent assay and spectrophotometrically, respectively. RESULTS Cyclosporine A treatment reduced renal expression and serum levels of Klotho, improved malondialdehyde and 8-hydroxy-deoxy guanosine levels, and also deteriorated renal function. Valsartan prevented CsA-induced oxidative stress as well as Klotho downregulation and could alleviate CsA-induced renal histological changes and function. CONCLUSIONS Administration of Val might lead to amelioration of CsA nephrotoxicity by probably diminishing CsA-induced renal Klotho downregulation and oxidative stress.

The aims of this study were to determine the effects of synbiotic (probiotic plus prebiotic) supplementation on total antioxidant capacity (TAC) and malondialdehyde (MDA) levels of human breastmilk.In this randomized, double-blind, placebo-controlled trial, 80 lactating mothers were randomly divided into two groups to receive a daily supplement of synbiotic (n=40) or a placebo (n=40) for 30 days. Information on dietary intake was collected from lactating women using the 24-hour recall method for 3 days before and after supplementation. The TAC was measured by using a Randox (Crumlin, County Antrim, United Kingdom) assay, and the MDA level of breastmilk as thiobarbitaric acid complexes was measured by the fluorometry method. Data analysis was carried out using Nutritionist IV (Axxya Systems, Stafford, TX) and SPSS (SPSS, Inc., Chicago, IL).The TAC of breastmilk increased significantly from 0.312±0.16 to 0.481±0.2 mmol/L in the supplemented group (p0.039), whereas it decreased from 0.317±0.18 to 0.255±0.13 mmol/L in the placebo group (p0.13). Although the MDA level decreased slightly from 1.62±0.69 to 1.6±0.95 μmol/L in the supplemented group, it increased significantly in the placebo group from 1.71±0.86 to 2.16±0.277 μmol/L after the experimental period (p0.001). Also, maternal vitamin A, E, and C, zinc, and selenium intake did not change significantly in both groups during the study period. Moreover, no significant correlation was found between weight for age Z-score of infants and TAC and MDA levels in breastmilk.Based on these results, synbiotic supplementation may have positive effects on the TAC and MDA levels in breastmilk; however, these findings require confirmation from future trials.

Objective: To study the effect of erythropoietin (EPO) treatment on renal and lung injury following renal ischemia/reperfusion (I/R). Materials and Methods: Thirty male Wistar rats were assigned to three groups of 10 rats each. The first group was sham-operated, the second was subjected to renal I/R (30 min of ischemia followed by 24 h of reperfusion). The third group was subjected to renal I/R and treated with EPO in two doses: the first dose 1 h prior to ischemia (1,000 U/kg) and the second dose 6 h after ischemia (1,000 U/kg). Results: The renal and lung tissue injury index, tissue serum blood urea nitrogen and creatinine (Cr) were higher in the renal I/R group compared to the renal I/R + EPO group; the difference was statistically significant (p < 0.05). Kidney and lung tissue glutathione peroxidase and superoxide dismutase levels were higher in the renal I/R + EPO group than the renal I/R group; the difference was also statistically significant (p < 0.05). Conclusion: The data showed that EPO pretreatment could be effective in reducing renal and lung injury following renal I/R and could improve the cellular antioxidant defense system. Hence EPO pretreatment may be effective for attenuating renal and lung injury after renal I/R-induced injury during surgical procedures, hypotension, renal transplantation and other conditions inducing renal I/R.

The clinical evaluation and management of impacted third molars remain challenging. The aim of the present study was to investigate possible associations between follicular tissue cytokines and radiographic manifestations of impacted third molar. The population included 72 patients who underwent surgical extraction of impacted third molars. All these patients underwent a preliminary panoramic radiograph. Levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and transforming growth factor beta (TGF-β) in tissue extracts were determined using ELISA. There were no significant differences between bony and tissue impaction as regards IL-1β, IL-6 and TGF-β levels. Moreover, the same results were obtained as far as the amount of pericoronal space and the presence or absence of a history of pericoronitis are concerned. These results suggest that radiographic findings or a history of pericoronitis are not associated with levels of expression of pro-inflammatory cytokines in patients undergoing surgical removal of impacted third molars. However, further studies are needed to address the possibility of variability during disease progression.

Objectives: To investigate the effect of lovastatin therapy and withdrawal on paraoxonase 1 (PON1) and arylesterase (ARE) activities, and low-density lipoprotein cholesterol (LDL-C) susceptibility to oxidation in people with type 2 diabetic nephropathy (T2DN). Design and methods: Lovastatin (20 mg/day) was administered to 30 people with T2DN for 90 days and then withdrawn for 30 days. PON1 and ARE activities were measured by the spectrophotometric method. Susceptibility of LDL-C to oxidation was determined as the production of conjugated dienes. Results: After 90 days of lovastatin intervention, PON1 and ARE activities and LDL-C lag phase were significantly increased (p = 0.004, 0.002, and

Introduction Hepatic ischemia/reperfusion (I/R) injury leads to free radical generation and acute inflammatory responses that cause liver damage, an important problem for liver transplantation. Pioglitazone is known to protect I/R injury in various tissues; however, the mechanism of cytoprotection is not well understood. This study investigated the effects of pioglitazone administration in a warm hepatic I/R model on tumor necrosis factor (TNF)-α level, tissue injury, and antioxidant enzyme activity. Materials and Methods Eighty wistar strain rats were divided into 4 groups (n = 20): Group 1 sham hosts; Group 2 hepatic I/R; Group 3 hepatic I/R + pioglitazone (10 mg/kg); and Group 4 hepatic I/R + vehicle. Rat livers were subjected to 30 minutes of ischemia followed by 6 hours of reperfusion. After reperfusion rats were humanely killed to obtain liver tissue to study glutathione peroxidase (GPx), superoxide dysmutase (SOD), malondialdehyde (MDA) levels and for histopathologic assessment. TNF-α, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in serum. Results Pioglitazone pretreatment significantly reduced liver enzyme content (ALT, 176.80 ± 13.75 vs 235.28 ± 31.92 and AST, 748.20 ± 79.29 vs 944.85 ± 101.87) and TNF-α level (9:8.60 ± 8.67 vs 138.28 ± 9.99) after I/R compared with the control group. MDA level (3.02 ± 0.37 vs 4.36 ± 0.38) and hepatocytic degeneration were reduced in the pioglitazone-treated group. GPx (2.40 ± 0.25 vs 1.36 ± 0.31) and SOD activity (2.22 ± 0.30 vs 1.40 ± 0.35) were significantly higher in the pioglitazone-treated group compared with the control group. Conclusion The present study showed that pioglitazone administration improved hepatic I/R injury that was associated with enhanced antioxidant enzyme activities and suppression of TNF-α, ALT, and AST levels. Because peroxisome proliferator-activated receptor-γ agonists are widely used to treat diabetic patients, it may be relatively easy to expand their clinical indication. However, further investigations will be required to delineate protective mechanisms by which pioglitazone attenuates hepatic tissue injury after I/R.

Considering the pathologic importance of oxidative stress and altered lipid metabolism in osteoarthritis (OA), this study aimed to investigate the effect of l-carnitine supplementation on oxidative stress, lipid profile, and clinical status in women with knee OA. We hypothesized that l-carnitine would improve clinical status by modulating serum oxidative stress and lipid profile. In this randomized double-blind, placebo-controlled trial, 72 overweight or obese women with mild to moderate knee OA were randomly allocated into 2 groups to receive 750 mg/d l-carnitine or placebo for 8 weeks. Dietary intake was evaluated using 24-hour recall for 3 days. Serum malondialdehyde (MDA), total antioxidant capacity (TAC) and lipid profile, visual analog scale for pain intensity, and patient global assessment of severity of disease were assessed before and after supplementation. Only 69 patients (33 in the l-carnitine group and 36 in the placebo group) completed the study. l-Carnitine supplementation resulted in significant reductions in serum MDA (2.46 ± 1.13 vs 2.16 ± 0.94 nmol/mL), total cholesterol (216.09 ± 34.54 vs 206.12 ± 39.74 mg/dL), and low-density lipoprotein cholesterol (129.45 ± 28.69 vs 122.05 ± 32.76 mg/dL) levels compared with baseline (P.05), whereas these parameters increased in the placebo group. Serum triglyceride, high-density lipoprotein cholesterol, and TAC levels did not change significantly in both groups (P.05). No significant differences were observed in dietary intake, serum lipid profile, MDA, and TAC levels between groups after adjusting for baseline values and covariates (P.05). There were significant intragroup and intergroup differences in pain intensity and patient global assessment of disease status after supplementation (P.05). Collectively, l-carnitine improved clinical status without changing oxidative stress and lipid profile significantly in women with knee OA.

Background High serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD. Methods CKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods. Results Serum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P

Background: Endotheline-1 (ET-1), an endothelial mediator, influences on mineral metabolism; especially vascular calcification in uremic patients. Objectives: The aim of the present study was to evaluate of ET-1, high-sensitivity C-reactive protein (hs-CRP) and mineral metabolites as the main factors for vascular calcification and inflammation in hemodialysis (HD) patients. Patients and Methods: In this cross-sectional study, 46 chronic stable HD patients were selected from nephrology departments of Tabriz University of Medical Sciences affiliated hospitals and classified based on phosphorus (P), Ca-P product (Ca × P) and intact Parathyroid Hormone (iPTH) levels. We evaluated fasting serum ET-1and hs-CRP levels by the standard methods and compared with 46 healthy control subjects. Results: The levels of serum hs-CRP and ET-1 were significantly higher in the patient’s group compared with controls (4.40 ± 1.26 vs. 1.38 ± 1.61, P < 0.0001, and 2.31 ± 0.87 vs. 0.75 ± 0.48, P < 0.0001, respectively) and with regard to Ca × P product cut-off point (3.99 ± 0.78 vs. 5.33 ± 1.64, P < 0.0001, and 2 ± 0.73 vs. 3.04 ± 0.73, P < 0.0001 respectively). ET-1 was correlated significantly with hs-CRP level (r = 0.776, P < 0.0001). Serum P, Ca × P and iPTH levels directly and Ca indirectly were correlated with serum ET-1 in HD patients (r = 0.932, P < 0.0001, r = 0.766, P < 0.0001, r = 0.514, P < 0.0001, r = -0.538, P < 0.0001 respectively). Multiple regression analysis demonstrated that serum P were independently associated with ET-1 levels (β = 0.932, P < 0.0001). Conclusions: Serum P and iPTH levels were independently associated with ET-1 and those may play a role in development of endothelial dysfunction in chronic kidney disease.

This paper1 was simultaneously submitted by the authors to "Transplantation" journal under the title "The Effects of Valsartan on Renal Klotho Expression and Oxidative stress in Alleviation of Cyclosporine Nephrotoxicity" and was accepted for publication in that journal. On the basis of BioImpacts policy in accordance with the Committee on Publication Ethics (COPE), any duplicate submission is considered as an ethical misconduct. The accepted manuscript in Transplantation shared considerable overlapping text and data (identical images and materials) with the published paper1 in BioImpacts. The Editor-in-Chief of BioImpacts, Prof. Y. Omidi, was alerted by the Editor-in-Chief of Transplantation, Prof. Jeremy R. Chapman, on such duplication. A comprehensive investigation through comparison of both papers was conducted by the editorial office of BioImpacts along with the Ethics Committee of Tabriz University of Medical Sciences (TUOMS) under Prof. M. R. Rashidi, who also acts as Director-in-Charge of BioImpacts and TUOMS Vice Chancellor of Research and Technology Affairs. As a result, they decided to retract this paper in line with the COPE recommendations. The authors were informed and advised on this serious ethical breach. Therefore, the paper is retracted at the request of authors, the aforementioned committee and the Editor-in-Chief of BioImpacts, even though the corresponding author believed that two papers were different in their aims, studied animals, and factors. By the way, they apologize for any inconvenience this may have caused. One of the conditions of submission of a paper to BioImpacts is that authors declare explicitly that "This manuscript has been exclusively submitted to this journal and is not under review or accepted for publication elsewhere". As such, this paper represents abuse of the scientific publishing system. As a peer-review multidisciplinary international "Publish Free" and "Access Free" journal, BioImpacts strongly adheres to the "Publication Ethics", and its foremost goal is to preserve the integrity of the scientific reports in the highest standards, therefore the journal takes all issues of publication misconduct seriously.

Methotrexate (MTX), a folate antagonist agent, is mainly used in treatment of malignant tumors and auto immune diseases and affects not only tumor cells, but also gastrointestinal mucosa. The present study was undertaken to determine whether lipoic acid (LA) could ameliorate methotrexate-induced oxidative intestine injury in rabbits. Twenty-one rabbits were randomly assigned into three groups: Group 1 (control group), Group 2 (received 20 mg/kg MTX), Group 3 (received MTX plus LA 75 mg/kg orally). On the 6th day rabbits were anesthetized and intestinal tissue sampled for pathologic and biochem- ical assessment. The intestinal tissue injury index and malondialdehyde (MDA) levels were lower in MTX+LA group as compared to the MTX group, and tissue glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were higher in MTX+LA group than in the MTX group (p