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Background Endothelial dysfunction (ED) has a well-known role in promoting vascular inflammation in Behçet disease (BD). α-klotho is involved in regulation of endothelial function, and its reduction has been reported to be associated with ED.  Objective To assess serum α-klotho in patients with BD, compared with healthy control individuals. Methods In a cross-sectional study, 55 patients with BD and 30 age- and sex-matched healthy controls were enrolled, and their serum levels of α-klotho were measured. Results Common clinical symptoms in patients with BD were oral aphthous ulcers, uveitis, and genital ulcers. Median (IQR) serum α-klotho levels in the BD and control groups were 0.30 (0.20–0.70) and 1.00 (0.70–2.52) ng/mL, respectively. The difference was statistically significant (P  = .005). No significant correlation was observed between serum α-klotho and age (r  = 0.194; P  = .14). Serum α-klotho levels in patients with uveitis were significantly lower. Conclusion α-klotho may have a role in the pathogenesis of ED and is a potential biomarker for uveitis in BD. [ABSTRACT FROM AUTHOR]

The dose‐dependent adverse effects of anticancer agents need new methods with lesser toxicity. The objective of the current research was to evaluate the efficacy of GLUT1 inhibitor, as an inhibitor of glucose consumption in cancer cells, in augmenting the efficiency of docetaxel with respect to cytotoxicity and apoptosis. Cell cytotoxicity was assessed by using methylthiazolyldiphenyl‐tetrazolium bromide (MTT) assay. Annexin V/PI double staining was employed to evaluate apoptosis percentage. Quantitative real‐time polymerase chain reaction (RT‐PCR) analysis was accomplished to detect the expression of genes involved in the apoptosis pathway. The IC50 values for docetaxel and BAY‐876 were 3.7 ± 0.81 and 34.1 ± 3.4 nM, respectively. The severity of synergistic mutual effects of these agents on each other was calculated by synergy finder application. It showed that the percentage of apoptotic cells following co‐administration of docetaxel and BAY‐876 increased to 48.1 ± 2.8%. In comparison without GLUT1 co‐administration, the combined therapy decreased significantly the transcriptome levels of the Bcl‐2 and Ki‐67 and a remarkable increase in the level of the Bax as proapoptotic protein(p < 0.05). Co‐treatment of BAY‐876 and docetaxel depicted a synergistic effect which was calculated using the synergy finder highest single agent (HSA) method (HSA synergy score: 28.055). These findings recommend that the combination of GLUT‐1 inhibitor and docetaxel can be considered as a promising therapeutic approach for the treatment of patients with lung cancer. [ABSTRACT FROM AUTHOR]

Background. Oral lichen planus (OLP) is a multifactorial chronic inflammatory condition with unknown etiology. This condition has been associated with Helicobacter pylori. This study aimed to investigate the relationship between the treatment of H. pylori infection and improvements in OLP lesions. Methods. In this cohort study, 42 patients with erosive or ulcerative OLP lesions were evaluated in terms of H. pylori infection using the H. pylori stool antigen (HpSA) test. The patients were divided into three groups. The first group consisted of 12 H. pylori-negative patients. The second group consisted of 21 H. pylori-positive patients receiving antibacterial treatment. The third group included nine H. pylori-positive patients not willing to receive treatment. All the three groups underwent the usual OLP treatment. Patients in the second and third groups were re-evaluated by the HpSA test after two months. The efficacy indexes and visual analog scale were used to evaluate clinical improvements. Results. The efficiency index and pain scores were affected by the intervention (P < 0.001). The logistic regression analysis showed that the severity index before treatment was significantly effective (OR = 0.745 (95% CI: 0.602-0.923; P = 0.007). No statistical significance for factors affecting other variables (P > 0.05) was obtained. Conclusion. Pain intensity was higher in patients with H. pylori than in those without H. pylori before treatment. Also, in patients with H. pylori, the treatment affects the complete recovery rate. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of onion juice on sodium-selenite induced cataract formation. Materials and Methods: Thirty-two 10-day-old Wistar-albino rat pups were divided into four equal groups. Group 1 received only subcutaneous saline injection. In Group 2, sodium-selenite (30 nmol / g body weight) was injected subcutaneously. In Group 3, subcutaneous sodium-selenite was injected and one drop 50% diluted fresh juice of crude onion was instilled every 8 h into the right eye for 14 days; the left eye received no treatment. Group 4 rats were similar to those of Group 3, the only difference being that of undiluted fresh juice of crude onion. The development of cataract was assessed. Rat lenses were analyzed for total antioxidant (TA) level, and for activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD). Results: Both eyes of all rats in Group 1 did not exhibit cataract formation . In Group 2, all rats developed Grade 3 cataract in the lenses of both eyes. The difference in exhibited cataract in the lens of the right eyes in all rats between Group 2 and any eyes of groups 3 or 4 were significant ( P = 0.001). The mean TA level and mean activities of SOD and GPX in Group 2 rat lenses were significantly lower than the values in lenses of all rats in Group 1 ( P = 0.001, 0.003, 0.001), and in the lenses of the right eyes of rats in Groups 3 and 4 ( P = 0.001, 0.020, 0.001). Conclusion: Instillation of onion juice into the rat eyes can effectively prevent selenite-induced cataract formation. This effect was associated with increased TA level, SOD and GPX activities in the lens.

Background. Lichen planus is considered a potentially malignant condition with an unknown etiology. This study aimed to determine the carcinoembryonic antigen (CEA) and IgG serum levels in different oral lichenoid lesions before and after treatment with local corticosteroids. Methods. Two groups of 23 individuals, including oral ulcerative lichenoid lesions patients and healthy ones, were evaluated. Toluidine blue staining and biopsy examinations were carried out while visual analog scale (VAS) was used to evaluate symptoms. By applying corticosteroids, CEA and IgG serum levels were determined before and three weeks after intervention and at the end of the study (9 weeks) with ELISA and turbidimetry methods, respectively. Results. Before the intervention, there was no significant difference in CEA serum levels between the control and case groups (P = 0.19). Moreover, the CEA serum levels indicated no significant difference before and after treatment in the case group (P = 0.30). While IgG serum level was significantly higher before the intervention (P = 0.01), it decreased significantly in the case group after treatment (P = 0.02). In addition, pain intensity reduced significantly in the case group (P = 0.05). According to statistics, 8.2% out of 21.7% of patients with positive staining results exhibited dysplasia signs. Conclusion. However, neither CEA nor IgG serum levels were different in patients diagnosed with or without dysplasia and positive or negative staining results (P > 0.05). IgG serum levels and pain severity effectively decreased in the oral ulcerative lichenoid lesions patients treated with local corticosteroids. Therefore, this treatment can be considered an effective and low-complication treatment modality for lichenoid lesions. [ABSTRACT FROM AUTHOR]

Background: Considering pathological significance of oxidative stress in systemic lupus erythematosus (SLE), current research aimed to evaluate the effects of melatonin supplementation on oxidative stress markers and disease activity in SLE. Method: In this randomised double‐blind, placebo‐controlled trial, 32 SLE females were selected and randomly assigned into two groups to take 10 mg/day melatonin or placebo for 12 weeks. Before and after trial, serum malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured and disease activity was determined by Systemic lupus erythematosus disease activity index 2000 (SLEDAI‐2K). Results: Twenty‐five patients (13 in the melatonin and 12 in the placebo groups) completed the trial. Melatonin supplementation caused significant reduction in serum MDA compared with baseline (P =.003) and placebo group (P =.004). Serum TAC level did not change significantly in the melatonin group compared with baseline and placebo group (P >.05). Furthermore, melatonin supplementation did not cause significant change in disease activity compared to baseline and placebo group (P >.05). Conclusion: This study demonstrated affirmative effects of melatonin in decreasing oxidative stress in SLE patients without any effect on disease activity. Further investigations are required to affirm these primitive findings and to achieve concise conclusions.What's knownFree radical damage and oxidative stress has a remarkable function in systemic lupus erythematosus (SLE) pathogenesis. Products derived from oxidative modification cascades are found in biological fluids and their redundancy has a correlation with disease activity and organ damage in SLE. Dietary supplements, which decrease oxidative stress, would be useful in managing SLE. Melatonin is a potent antioxidant and has anti‐inflammatory and immunomodulatory characteristics. Limited in vitro and animal studies are available indicating desirable effects of melatonin in preventing from SLE organ damage, thereby opening a new area of investigation that can contribute to using melatonin as a therapy or co‐therapy for SLE.What's newMelatonin supplementation caused significant reduction in serum MDA compared with baseline and placebo group. Serum TAC level did not change significantly in the melatonin group compared with baseline and placebo group. Furthermore, melatonin supplementation did not cause significant change in disease activity compared to baseline and placebo group. [ABSTRACT FROM AUTHOR]

Abstract Abstract Hyperlipidemia and increased degree of oxidative stress are among the important risk factors for Atherosclerosis in renal transplant recipients (RTR). The Medical treatment of hyperlipidemia in RTR because of drugs side effects has been problematic, therefore alternative methods such as using of Garlic as an effective material in cholesterol lowering and inhibition of LDL Oxidation has been noted. For evaluation of garlic effect on RTR, 50 renal transplant patients with stable renal function were selected and divided into 2 groups. They took one clove of garlic (1 gr) by chewing or swallowing for two months, after one month wash-out period, they took garlic by the other route. Results indicated that although lipid profile, BUN, Cr, serum levels of cyclosporine and diastolic blood pressure did not change, Systolic blood pressure decreased from138.2 to 132.8 mmHg (p=0.001) and Malondialdehyde (MDA) decreased from 2.4 to1.7 nmol/ml (p=0.009) by swallowing route, Cholesterol decreased from 205.1 to 195.3 mg/dl (p=0.03), triglyceride decreased from 195.7 to 174.8 mg/dl (p=0.008), MDA decreased from 2.5 to 1.6 nmol/ml (p=0.001), systolic blood pressure decreased from 137.5 to 129.8 mmHg (p=0.001), diastolic blood pressure decreased from 84.6 to 77.6 mmHg (p=0.001) and Cr decreased from 1.51 to 1.44 mg/dl (p=0.03) by chewing route too. However HDL, LDL and cyclosporine serum levels had no significant differences by both of swallowing and chewing routes. We conclude that undamaged garlic (swallowed) had no lowering effect on lipid level of serum. But Crushed garlic (chewed) reduces cholesterol, triglyceride, MDA and blood pressure. Additionally creatinine reduced without notable decrease in cyclosporine serum levels may be due to cyclosporine nephrotoxicity ameliorating effect of garlic.

Abstract Malnutrition, anemia and increased atherosclerosis are the main causes of mortality in hemodialysis patients. Therapies designed to improve the disorders might therefore be expected to improve outcome. The effects of Nandrolone Decanoate (ND), in 64 stable hemodialysis patients, were studied with respect to the following parameters: nutritional status, hematological indexes, lipid profiles including serum levels of lipoprotein(a) [Lp(a)] in terms of differences in apolipoprotein(a) [apo(a)]. The patients were treated with ND at dose of 100 mg/I.M./week for 4 months. After 2 and 4 months of treatment the elevations in the serum levels of albumin (p < 0.0001), creatinine (p < 0.009), hemoglobin (p < 0.03), hematocrit (p < 0.03), cholesterol (p = 0.007) and triglyceride (p < 0.04) were noticed. Marked decrease in the concentration of high-density lipoprotein cholesterol (p = 0.007) and Lp(a) (p < 0.0001) were also found. These effects after 2 months of treatment withdrawal were relatively constant. By dividing patients according to the baseline Lp(a) levels and molecular weight of apo(a) isoform, it was noticed that the decrease in serum Lp(a) was significant in patients with high Lp(a) (>30 mg/dl) than those of with low Lp(a) (

Considering the importance of toll-like receptor (TLR) 4 and oxidative stress in the pathogenesis of autoimmune disorders, present study was designed to assess serum TLR4, 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a marker of oxidative DNA damage, and total antioxidant capacity (TAC) in rheumatoid arthritis (RA) patients and to study their relation with disease activity and their predictive potential. 44 RA patients and 44 matched controls were studied. Disease activity score (DAS-28) was assessed. Serum TLR4, 8-OHdG and TAC were measured. The mean age of patients was 44 ± 10.4 years, 33 females and 11 males with and disease duration 5.5 ± 3.8 months. The mean DAS-28 was 4.6 ± 0.6 (3.45–6.01). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were both positive in 20 patients. Compared to control, the mean ± SD of serum TLR4 (2.41 ± 4.50 vs. 1.20 ± 1.67 ng/ml), and 8-OHdG (67.67 ± 20.57 vs. 45.34 ± 30.61 ng/ml) were significantly higher in patients (p < 0.001); whilst serum TAC (1.3 ± 0.5 vs. 2.01 ± 0.55 µmol/L) was significantly lower (p < 0.001). TLR4, 8-OHdG were significantly increased and TAC decreased in patients with positive RF/anti-CCP compared to negative (p < 0.001, p = 0.005 and p = 0.036 respectively). TLR4 was significantly higher in patients with higher DAS-28 (p = 0.003) and both significantly correlated (p < 0.001). Areas under the ROC curve of TLR4 (0.87; 95%CI: 0.78–0.96) and 8-OHdG (0.88; 95%CI: 0.79–0.97) were greater than that of TAC (0.19, 95%CI: 0.09–0.29) (p < 0.001). The TLR4, 8-OHdG and TAC showed high predictive value in RA disease. TLR4 can be remarked as a sensitive and specific marker for determining disease activity in RA. [ABSTRACT FROM AUTHOR]

Objective: Behcet's disease (BD) is a chronic inflammatory disorder characterized by recurrent oral and genital aphthous ulcers, uveitis and skin lesions. Oxidative stress and inflammation have important role in the pathogenesis of BD. The aim of this study was to assess the effect of Nigella sativa (NS) oil administration on malondialdehyde (MDA), total anti-oxidant capacity (TAC), tumor necrosis factor-α (TNF-α), IL-10 and high sensitivity C-reactive protein (hs- CRP) levels in patients with BD. Materials and Methods: In this randomized, double-blind and placebo-controlled clinical trial, 96 BD patients were randomly assigned to NS or placebo groups. Study groups received 1000 mg/day NS oil and placebo soft gels for 8 weeks. Serum levels of TNF-α, IL-10, hs-CRP, MDA and TAC were measured before and after treatment. Results: Eighty-nine individuals completed the study. Significant decreases in the serum levels of MDA and increases in the serum levels of TAC were found in the NS group. However, differences in the changes of MDA and TAC in the NS and placebo groups were not significant. Pre- and post-intervention changes of TNF-α, IL-10 and hs-CRP levels in the NS group were non-significant. Conclusion: NS 1000 mg per day is probably not effective in reducing the inflammatory and oxidative markers in BD. [ABSTRACT FROM AUTHOR]

Objective: Considering the important role of serum soluble receptor for advanced glycation end product (sRAGE/RAGE)-ligand system in rheumatoid arthritis (RA), this study aimed to evaluate serum sRAGE levels in RA patients compared to healthy subjects and to assess whether there is an association between sRAGE levels and disease characteristics in RA. Methods: In this cross-sectional study, 60 RA patients according to the ACR/EULAR 2010 criteria and 30 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and disease activity score 28 (DAS-28) measure of disease activity was assessed. Serum sRAGE level was measured using ELISA kit. Results: The mean ± SD age of patients and controls was 54.86 ± 11.65 and 50.71 ± 3.72 years, respectively). Serum sRAGE level was significantly higher in RA patients (median [25th and 75th percentiles], 1000.3 [792.00, 1486.8]) compared to healthy controls (median [25th and 75th percentiles], 293.25 [220.35, 364.24]) (p<.001). There was significant difference in serum sRAGE level according to the activity of disease (p<.001). There were significant positive correlations between serum sRAGE level with disease activity (r=0.67, p<.001), ESR (r=0.411, p=.001) and CRP (r=0.273, p=.035). There were no significant correlations between serum sRAGE level with demographic characteristics as well as biochemical measurements including serum creatinine, BUN, RF, and Anti-CCP (p>.05). Conclusions: Our study revealed higher serum sRAGE levels in RA patients compared to healthy controls, which correlated positively with disease activity. [ABSTRACT FROM AUTHOR]

This work aimed to evaluate serum pentraxin 3 (PTX3) levels in rheumatoid arthritis (RA) patients and to study the association with the disease activity. Sixty RA patients and 26 matched controls were included. In patients, clinical examination was performed and disease activity score (DAS28) assessed. Serum PTX3, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured. The mean age of the patients was 54.9 ± 11.7 years, and the median (Min–Max) of disease duration was 24 (3.96–60) months and 91.7% were females. The mean DAS28 was 4.16 ± 1.77, the ESR was 38.6 ± 23.03 mm/1st h, CRP was 14.9 ± 8.6 mg/l, RF was 49.6 ± 28.1 IU/ml and the median anti-CCP was 375. Serum PTX3 level was significantly higher in RA patients (2.82 ± 0.48 pg/ml) compared to controls (2.56 ± 0.29 pg/ml) (p = 0.003). There was a significant difference in serum PTX3 level according to the disease activity: remission (2.49 ± 0.16 pg/ml), low (2.61 ± 0.33 pg/ml), moderate (2.90 ± 0.53 pg/ml) and high (3.01 ± 0.51 pg/ml) (p = 0.016). There was a significant correlation between serum PTX3 level with disease activity (r = 0.39, p = 0.002) and CRP (r = 0.49, p < 0.001). There was no significant correlation between serum PTX3 level and the RF (r = 0.25, p = 0.054), anti-CCP (r = 0.18, p = 0.17) and ESR (r = 0.09, p = 0.51). PTX3 and CRP showed a good sensitivity and specificity in predicting RA disease (p = 0.006 and p < 0.001, respectively). PTX3 can be considered as a marker of a positive acute phase response and may serve as a potential novel biomarker for detecting RA activity. [ABSTRACT FROM AUTHOR]

Objective(s): Cisplatin is an effective antineoplastic agent; its clinical utility, however, is limited by a few salient toxic side effects like nephrotoxicity. This study aimed to determine the potential protective effects of tangeretin, a citrus-derived flavonoid, against renal tubular cell injury in cisplatin-induced renal toxicity of rats. Materials and Methods: Tangeretin was injected intraperitoneally at 2.5 and 5 mg/kg doses for 10 days, and a single dose of cisplatin (8 mg/kg) was injected on the 7th day. Tests of kidney function and tubular injury in renal tissues and urine together with oxidative stress and inflammation markers were examined. Results: Tangeretin ameliorated cisplatin-induced elevations in serum creatinine, BUN, and histopathologic changes. It also attenuated kidney oxidative stress elicited by cisplatin as demonstrated by reduced MDA and increased GSH, CAT, and SOD activities, elevated Nrf2 expression and protein levels of its downstream effectors, HO-1 and NQO-1. Tangeretin further alleviated inflammation evoked by cisplatin as indicated by reduced NF-κB p65 subunit phosphorylation with a simultaneous decrement in its downstream effectors IL-1β and TNF-α expression and protein levels. Moreover, it declined caspase-3 protein levels and TUNEL positive cells in the kidneys, the markers of apoptosis and DNA fragmentation, thus improving renal endurance. Additionally, tangeretin mitigated renal levels of KIM-1 and NGAL, as well as urinary cystatin C and β2-microglobulin concentrations, the markers of renal tubular injury. Conclusion: Collectively, these data signify the binary profit of tangeretin: enhancement of renal protective mechanisms against cisplatin and attenuation of renal tubular cell injuries induced by the agent. [ABSTRACT FROM AUTHOR]

Abstract: Due to the association of oxidative stress and telomere shortening, it was aimed in the present study to investigate the possibility whether cyclosporine‐A exerts its nephrotoxic side effects via induction of oxidative stress‐induced renal telomere shortening and senescent phenotype in renal tissues of rats. Renal oxidative stress markers, 8‐hydroxydeoxyguanosine, malondialdehyde, and protein carbonyl groups were measured by standard methods. Telomere length and telomerase activity were also evaluated in kidney tissue samples. Results showed that cyclosporine‐A treatment significantly (P < 0.05) enhanced renal malondialdehyde, 8‐hydroxydeoxyguanosine, and protein carbonyl groups levels, decreased renal telomere length, and deteriorated renal function compared with the controls. Renal telomerase activity was not affected by cyclosporine‐A. Renal telomere length could be considered as an important parameter of both oxidative stress and kidney function. Telomere shortening and accelerated kidney aging may be caused by cyclosporine‐induced oxidative stress, indicating the potential mechanism of cyclosporine‐induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study aimed to follow up patients with polymyositis (PM) and/or dermatomyositis (DM) to determine survival rate, pattern of disease, response to treatment, malignancy incidence and poor prognostic factors (PPFs). Method: A total of 76 patients with PM (n = 47) and/or DM (n = 29) based on Bohan and Peter diagnostic criteria referred to the Imam‐Reza Hospital were followed up from 2004 to 2016. The follow‐up period was considered from diagnosis to patient′s death or last visit. All patients underwent physical examinations and data including age, sex, disease duration, disease subtype, pattern of disease, PPFs and malignancy incidence were collected. Results: Mean age at diagnosis was 45.49 ± 10.88 years and women were predominant (84.2%). Course of disease in the majority of patients (52.6%) was polyphasic, followed by monophasic (31.6%) and chronic‐progressive (5.3%). The 1‐, 5‐ and 10‐year survival rates were 96%, 93% and 92%, respectively. Delay in treatment and dysphagia were common PPFs in the present study. The majority of patients responded to treatment (88.2%) and there were significant differences in cancer and dysphagia between responders and non‐responders to treatment (P < 0.05). The most common cause of death was cancer in four of eight deaths. There was significant difference in survival rates between patients with and without pulmonary involvement (P = 0.001). Moreover, the survival rates were significantly lower in patients with malignancy (P = 0.001). Conclusion: Presence of dysphagia and cancer were associated with poor response to treatment. Pulmonary involvement and cancer incidence significantly affect survival rate. Furthermore, since cancer is the most common cause of death, so this study emphasizes the importance of careful cancer screening in these patients. [ABSTRACT FROM AUTHOR]

Statins are widely used drugs for their role in decreasing cholesterol in hypercholesterolemic patients. Statins through inhibition of Hydroxy Methyl Glutaryl-CoA Reductase (HMGCR), the main enzyme of the cholesterol biosynthesis pathway, inhibit mevalonate pathway that provides isoprenoids for prenylation of different proteins such as Ras superfamily which has an essential role in cancer developing. Inhibition of the mevalonate/isoprenoid pathway is the cause of the cholesterol independent effects of statins or pleotropic effects. Depending on their penetrance into the extra-hepatic cells, statins have different effects on mevalonate/isoprenoid pathway. Lipophilic statins diffuse into all cells and hydrophilic ones use a variety of membrane transporters to gain access to cells other than hepatocytes. It has been suggested that the lower accessibility of statins for extra-hepatic tissues may result in the compensatory induction of mevalonate/isoprenoid pathway and so cancer developing. However, most of the population-based studies have demonstrated that statins have no effect on cancer developing, even decrease the risk of different types of cancer. In this review we focus on the cancer developing “potentials” and the anti-cancer “activities” of statins regarding the effects of statins on mevalonate/isoprenoid pathway in the liver and extra-hepatic tissues. [ABSTRACT FROM AUTHOR]

Hydroxy-Methyl-Glutaryl-CoA reductase (HMGCR) -- the main enzyme of the cholesterol biosynthesis pathway -- is mostly inhibited by statins in hepatocytes. In spite of the other tissues, liver utilizes cholesterol in different ways such as the synthesis of bile acids, excretion in to the intestine and synthesis of lipoproteins. Therefore, statins theoretically alter these pathways; although, there have not been such effects. In this review, we aim to show the roles of extrahepatic tissues, in particular intestine, adipose and cutaneous tissues in providing the cholesterol after reduction of the whole body cholesterol content by statins. [ABSTRACT FROM AUTHOR]