Search

Purpose: Our objective was to compare the serum Adropin levels between patients with wet-type Age-Related Macular Degeneration (AMD) and otherwise healthy individuals., Method: The study included 45 patients with wet-type AMD and 45 individuals without age-related macular degeneration. Patients with co-morbidities such as diabetes, hypertension, autoimmune diseases, and a previous history of visual impairment; were excluded. FBS, Hemoglobin A1C (HbA1C), lipid profile, and serum Adropin level were checked., Results: The mean serum Adropin level of patients with wet-type AMD was significantly lower than the control group (P-value < 0.001). Also, the mean High-sensitivity C-reactive protein ( hsCRP) level and High Density Lipoprotein (HDL) were significantly higher in wet-type AMD patients (P-value = 0.031 and < 0.001 respectively)., Conclusions: In our study, wet-type AMD was associated with a lower level of serum Adropin. Because of Adropin involvement in glucose metabolism and age-related changes, it may have a role in the pathogenesis of AMD, but it requires more investigations at the molecular level to elucidate its function., (© 2024. The Author(s).)

Remdesivir (REM) and dexamethasone (DEX) both have been used to treat coronavirus disease 2019 (COVID-19). The present study aimed to evaluate the effects of REM and DEX on kidney structure and function with particular focus on the probable renal sirtuin-1 (SIRT1) expression alteration in rats. Twenty-four male Wistar rats were divided into four groups, as follows: group A (control) received normal saline (5 mL/kg/day for 10 days); group B (REM) received REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days); group C (REM + DEX) received both REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days) and DEX (7 mg/kg/day, for 10 days); group D (DEX) received DEX (7 mg/kg/day for 10 days). Renal SIRT1 expression and kidney structure and function-related factors were evaluated by standard methods. The mean levels of urea in the REM + DEX group (60.83 ± 6.77, mg/dL) were significantly higher than in the control (48.33 ± 3.01, mg/dL; p = 0.002) and DEX (51.22 ± 4.99, mg/dL; p = 0.018) groups. The mean levels of creatinine in the REM (0.48 ± 0.08, mg/dL) and REM + DEX (0.50 ± 0.04, mg/dL) groups were higher than in the control group (48.33 ± 3.0 mg/dL) significantly (p = 0.022 and p = 0.010, respectively). The renal SIRT1 expression was significantly (p = 0.018) lower in the REM + DEX group (0.36 ± 0.35) than in the control group (1.34 ± 0.48). Tubulointerstitial damage (TID) scores in REM + DEX-treated rats (2.60 ± 0.24) were significantly higher than in the control (0.17 ± 0.17, p = 0.001) and DEX (0.50 ± 0.29, p = 0.005) groups. The administration of DEX and REM might lead to kidney injury associated with SIRT1 downregulation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recurrent seizures in epilepsy may lead to progressive neuronal damage, which can diminish health-related quality of life. Evaluation and control of pathological processes in the brain is valuable. It seems imperative that new markers and approaches for seizure alleviation be discovered. Klotho (Kl), an antiaging protein, has protective effects in the brain against neurological disorders. It may also have antiseizure effects by improving creatine transfer to the brain, upregulating excitatory amino acid transporters, and inhibiting insulin/insulin-like growth factor-1 (IGF-1), Wingless (Wnt), transforming growth factor-beta (TGF-β), and retinoic-acid-inducible gene-I (RIG-I)/nuclear translocation of nuclear factor-κB (NF-κB) pathways. Stimulation and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and apoptosis signal-regulating kinase 1 (ASK1)/p38 mitogen‑activated protein kinase (MAPK) signaling pathways could also be considered other possible antiseizure mechanisms of Kl. In the present review, the roles of Kl in the central nervous system as well as its possible anti-seizure properties are discussed for the first time., Competing Interests: Declaration of Competing Interest Nasrin Ranjbar and Mohammadreza Raeisi are equally contributed as first authors. The authors declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-β levels in SLE patients and evaluate it as a potential biomarker in assessing SLE activity and predicting organ involvement., Methods: In a cross-sectional study, 60 patients diagnosed with SLE and 30 age- and sex-matched healthy controls were enrolled. Disease activity of SLE patients was assessed by the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K). Serum levels of salusin-ß were measured using a human salusin-ß enzyme-linked immunosorbent assay kit., Results: Serum salusin-β levels in SLE and control groups were 474.2 ± 117.1 pg/ml and 157.7 ± 88.7 pg/ml, respectively. The difference was significant (P = 0.001). There was no significant correlation between serum salusin-β levels with age (r =  - 0.06, P = 0.632) and SLEDAI (r =  - 0.185, P = 0.158). In patients with nephritis and thrombosis, serum salusin-β was significantly higher. In addition, in patients with serositis, serum salusin-β was significantly lower. Multiple linear regression analysis showed that serum salusin-β levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis., Conclusions: Our findings showed that salusin-β might have a possible role in the pathogenesis of SLE. Salusin-β may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-β levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-β levels with age and SLEDAI. • Serum salusin-β levels retained a significant association with nephritis and thrombosis., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

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 IC 50 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., (© 2023 Wiley Periodicals LLC.)

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., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Author(s).)

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., (©2022 The Author(s).)

Purpose: To evaluate the serum vitamin D levels of patients with vernal keratoconjunctivitis (VKC)., Method: A total of 39 VKC patients (21 males and 18 females) and 32 healthy individuals (19 males and 13 females) were enrolled in this study with the mean age of 18.38 ± 8.83 and 21.6 ± 9.43, respectively. The type and the grade of VKC were identified for each patient and serum 25-hydroxyvitamin D (25(OH)D) levels of all subjects were evaluated., Results: The patients affected by VKC had statistically significant lower 25(OH)D levels (27.64 ± 8.50 ng/mL) than healthy subjects group (35.96 ± 11.34 ng/mL) ( p  = 0.001). A reverse correlation was found between the serum vitamin D levels and the severity of the VKC but it was not statistically significant ( r  = -0.159, p  = 0.33). Besides, there were a few cases with severe and very severe VKC (2 in grade 3 and 4 in grade 4). Patients with the mixed type of the disease had lower serum vitamin D levels in comparison to tarsal and limbal forms but the difference was not statistically significant ( p  = 0.38)., Conclusion: This study shows that the patients affected by VKC have lower vitamin D levels in comparison to healthy subjects and the screening of all patients with VKC for vitamin D levels seems rational.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that may emerge at a young age and often lasts for life. It often goes through phases of recurrence and remission and has a devastating effect on quality of life. The exact etiology of the disease is still unclear, but it appears that an inappropriate immune response to intestinal flora bacteria in people with a genetic predisposition may cause the disease. Managing inflammatory bowel disease is still a serious challenge. Oxidative stress and free radicals appear to be involved in the pathogenesis of this disease, and a number of studies have suggested the use of antioxidants as a therapeutic approach. The antioxidant and anti-inflammatory properties of some trace elements have led some of the research to focus on studying these trace elements in inflammatory bowel disease. Zinc and selenium are among the most important trace elements that have significant anti-inflammatory and antioxidant properties. Some studies have shown the importance of these trace elements in inflammatory bowel disease. In this review, we have attempted to provide a comprehensive overview of the findings of these studies and to gather current knowledge about the association of these trace elements with the inflammatory process and inflammatory bowel disease.

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 known Free 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 new Melatonin 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., (© 2021 John Wiley & Sons Ltd.)

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.

Background: The present study aimed to evaluate serum YKL-40 levels in patients with rheumatoid arthritis (RA) compared to healthy subjects and to search whether there is an association between YKL-40 levels and disease characteristics in RA., Methods: In this cross-sectional study, 60 RA patients based on 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 YKL-40 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 YKL-40 level was significantly higher in RA patients (951.63±639.98 pg/mL) compared to healthy controls (444.92±150.37 pg/mL) (P<0.001). There was no significant difference in serum YKL-40 level according to the activity of disease (p>0.05). There were significant positive correlations between serum YKL-40 level with disease activity (r=0.347, P=0.007) and rheumatoid factor (r=0.396, P=0.002). There were no significant correlations between serum YKL-40 level with demographic characteristics as well as biochemical measurements including serum creatinine, blood urea nitrogen, erythrocyte sedimentation rate, C-reactive protein and anti-cyclic citrullinated peptide., Conclusion: Our study revealed higher serum YKL-40 levels in RA patients compared to healthy controls, which correlated positively with disease activity. Therefore, YKL-40 can be considered as a novel biomarker for disease activity estimation in RA., Competing Interests: The authors declare that they have no conflict of interest.

Background: One of the important factors in the occurrence of acute kidney injury (AKI) among renal transplant patients (RTPs) is ischemia reperfusion injury (IRI). The current study aimed at determining the anti-inflammatory and anti-oxidative effects of melatonin on the complications of IRI and the level of Klotho expression in these patients., Methods: A total of 40 renal transplant candidates were randomly assigned into placebo or melatonin group receiving the same dose of 3 mg/day. In order to measure serum melatonin levels, inflammatory and oxidative stress factors, renal function biomarkers, and Klotho gene/protein expression, venous blood samples were taken from patients over two different time points, i e, 24 h before the transplantation and at discharge from hospital., Results: Melatonin was associated with improvement in renal transplantation, since the serum level of neutrophil gelatinase-associated lipocalin, as a renal functional marker, significantly decreased (P < .001). The effect of melatonin as a suppressor of inflammation and oxidative stress was also evident in the melatonin group due to a significant reduction in the serum levels of MDA, CP, 8-OHdG, and TNF-α markers (P < .001)., Conclusions: Reduction in serum levels of renal function and oxidative stress/inflammatory markers in the melatonin group indicates that melatonin can inhibit IRI outcomes in RTPs through its anti-oxidant and anti-inflammatory properties. However, these properties do not appear as a result of influence on the level of Klotho gene/protein expression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hyperlipidemia and oxidative stress are indispensable features of chronic kidney disease (CKD) that favor the development of atherogenic plaques and cardiovascular disease (CVD). A number of vasoactive mediators including proprotein convertase subtilisin-kexin type 9 (PCSK9), endothelin-1, nitric oxide, and angiotensin II have fundamental roles in the pathophysiology of atherosclerotic events; moreover, their levels are affected by dyslipidemia and oxidative stress due to renal dysfunction. Therefore, therapeutic measures aimed at correcting dyslipidemia and alleviating oxidative stress could potentially protect against CVD in CKD patients. In this review, we discuss the relation between dyslipidemia, oxidative stress, and vasoactive mediators as well as the available treatment options against these disturbances in CKD patients.

Introduction: Kidney involvement is a hallmark of systemic lupus erythematosus (SLE) and evaluation of its inflammatory response is demanding. It was the aim of the present study to evaluate the levels of CXCL10 and vitamin D in serum samples of cases with active lupus nephritis (LN)., Methods: Fifty lupus patients were enrolled in our study, 25 patients had lupus nephritis and 25 patients were without evidence of LN. Thirty-nine healthy subjects were also participated as a control group. Complete biochemical and serological parameters were measured and their correlation with serum levels of vitamin D and CXCL10 were assessed in the studied groups., Results: Serum levels of CXCL10 were significantly elevated (P≤ 0.020), while vitamin D were diminished in SLE group and active LN as compared with healthy controls and SLE patients without nephritis, respectively. CXCL10 correlated with SLE disease activity index (SLEDAI) and renal activity (P < .05), while vitamin D correlated with C3 and anti-dsDNA antibody (P < .05). Based on the receiver operator characteristic (ROC) curve analysis, CXCL10 and vitamin D levels were not better than conventional biomarkers for discriminating LN patients from non-nephritis SLE patients; however, they could differentiate most of SLE cases from healthy individuals with area under the curve (AUC) ≥ 0.703 (P < .05)., Conclusion: Results indicated the importance of elevated levels of CXCL10 and deficiency of vitamin D on the pathogenesis of active LN disease.

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.

Cisplatin is a broadly prescribed anti-tumor agent for the treatment of diverse cancers. Therapy with cisplatin, however, is associated with various adverse effects including nephrotoxicity and ototoxicity. AMP kinase (AMPK), an evolutionarily conserved enzyme, functions as the fundamental regulator of energy homeostasis. While AMPK activation protects normal tissues against cisplatin-induced toxicities, its impact in cancer is context-dependent and there is no single, uniform role for AMPK. On one hand, some report that AMPK activation augments cisplatin-induced apoptosis in cancer, while on the other hand, few reports indicate that AMPK activation rescues cancer cells from the cytotoxicity induced by cisplatin. Here we review the most salient signaling pathways regulated by AMPK with an emphasis on their relation to cisplatin toxicity and yet discuss context-dependent functions of AMPK in cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Mild traumatic brain injury (mTBI) is a major public health risk for developing anxiety-related disorders and hypothalamus-pituitary-adrenal (HPA) axis dysregulation in humans. Extensive research has shown that dietary intake or supplementation of the natural flavonoid quercetin might be useful for treating anxiety-related symptoms. The objectives of this study were to determine whether quercetin treatment can attenuate anxiogenic-like behaviors and normalize HPA axis function in mice with mTBI. Animals subjected to mTBI were treated daily with quercetin (50 mg/kg) or diazepam (positive control, 3 mg/kg) for 14 days. Four behavioral tests (open field, plus maze, light-dark box, and zero maze) were used to assess anxiety-related behaviors in mice. To evaluate HPA axis function, adrenocorticotropic hormone and corticosterone were measured in the serum of mice after the anxiety tests. Quercetin treatment was found to significantly reduce anxiety-like behaviors in mTBI-induced mice. A strength of this study is the consistency of results among anxiety tests. The dysregulation of the HPA axis in mTBI-induced mice treated with quercetin was also attenuated, with decreased levels of adrenocorticotropic hormone and corticosterone. The effects of quercetin were comparable with those of diazepam treatment. Taken together, these results suggest that quercetin might be useful for treating anxiety-related symptoms and HPA axis hyperreactivity in patients with mTBI.

Objectives: 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., Competing Interests: All authors declare no conflicts of interest.

Chitosan is a cationic polysaccharide and multi-potential polymer with the ability to interact with other natural and synthetic polyanionic/polymeric compounds, with or without a cross-linking agent. It has been able to composite nano-microparticles with a variety of features. This compound has the ability to carry quercetin, as an anti-tumor subject, through the various epithelial systems and release in the sustained and controlled state to the target site. This paper reviews published studies on detailed physicochemical properties of chitosan and quercetin in the fight against the tumor. This also focused on how the chitosan polymer interacts with other polymeric and polyanion species in order to improve its efficiency to make a more suitable capsule or matrix for a variety of drugs, especially quercetin, in oral delivery systems., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: There is increasing evidence showing that mild traumatic brain injury (mTBI) is associated with increased depression-related disorders in humans. Recent studies suggest that dietary intake or supplementation of natural flavonoids like hesperidin can be used for therapy of patients with brain injury and depression. However, the exact mechanisms by which hesperidin indicates its neuroprotective effects are not fully understood. The purpose of this study was to explore the influence of hesperidin on depression-related symptoms in a mouse model of mTBI, and that what mechanisms are primarily involved in the antidepressant effects of this bioflavonoid., Main Methods: Ten days after mTBI-induction, mice received oral hesperidin treatment (50 mg/kg/14 days), then animals were subjected to different depression tests including sucrose preference test, forced swim test, novelty-suppressed feeding test, and tail suspension test. We also measured levels of tumor necrosis factor (TNF)-α, interleukin-(IL)-1β, malondialdehyde (MDA), and brain-derived-neurotrophic-factor (BDNF) in the hippocampus., Key Findings: Our results show that mTBI induction induced depressive-like behaviors in mice by increasing inflammatory cytokines (IL-1β and TNF-α) and oxidative stress marker (MDA), and reducing BDNF levels in the hippocampus. Interestingly, hesperidin treatment was effective to significantly reduce depression-related symptoms in mTBI-induced mice. In addition, hesperidin decreased the levels of IL-1β, TNF-α and MDA, and increased BDNF levels in the hippocampus. The major strength of our study is that four behavioral tests gave similar results., Significance: This study suggests that the antidepressant-like effect of hesperidin may be mediated, at least in part, by decreased neuroinflammation and oxidative damage, and enhanced BDNF production in the hippocampus., (Copyright © 2018. Published by Elsevier Inc.)

Introduction: Nontraditional risk factors for cardiovascular disease (CVD), including mineral disorder, high fibroblast growth factor 23 (FGF23), low klotho, and low soluble TWEAK could predict the incipient risk of CVD in chronic kidney disease (CKD). The present study evaluates the effect of sevelamer on soluble tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and klotho levels in adenine-induced CKD rats., Methods and Materials: Normal control rats without sevelamer were compared with 3 groups of adenine-induced CKD rats, including CKD rats without sevelamer, CKD rats treated with 3% sevelamer, and rats receiving adenine and 3% sevelamer concurrently. After 4 weeks of sevelamer treatment, serum levels of klotho and soluble TWEAK were measured, along with biochemical parameters related to kidney function., Results: Sevelamer significantly reduced serum levels of phosphate and increased serum levels of klotho and soluble TWEAK. Decreased levels of phosphate were negatively correlated with elevated levels of klotho and soluble TWEAK (r = -0.70, P = .003; r = -0.58, P = .02; respectively) in serum., Conclusions: Sevelamer successfully reduced serum levels of phosphate, and meanwhile, it led to an elevation in serum levels of klotho and soluble TWEAK in rat models of CKD.

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 <0.05) compared with the CKD control rats. A dose-dependent decrease in serum FGF-23 levels was observed, and the most significant results were obtained in rats receiving 3% sevelamer compared with the CKD control rats (142.60±83.95 pg/mL vs. 297.15±131.10 pg/mL, P <0.01)., Conclusions: Higher sevelamer doses significantly reduced serum phosphate and FGF-23 levels in adenine-induced CKD rats., Competing Interests: No potential conflict of interest relevant to this article was reported.

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., (© 2018 Wiley Periodicals, Inc.)

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., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Cardiovascular disease, as the leading cause of patient death with chronic kidney disease, could be predicted by carotid atherosclerosis. The aim of the present study was to evaluate a possible relationship between serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and Vitamin D levels with mean right/left carotid intima-media thickness (cIMT), in the hemodialysis (HD) patients. In this cross-sectional study, serums were obtained from 50 stable chronic HD patients and 39 healthy controls. The serum levels of sTWEAK, Vitamin D, intact parathyroid hormone (iPTH) in both groups, and cIMT were determined in HD patients by standard methods. Serum levels of sTWEAK were higher [808.8 (521.6-5032.4) pg/ml vs. 664.4 (487.4-2955.8) pg/ml ( p  = 0.006)] and Vitamin D levels were lower [13.4 (2.5-153) ng/ml vs. 27.8 (18.4-59.0) ng/ml ( p  = 0.001)] in the hemodialysis patients than in the healthy control. No important correlation was found between sTWEAK Vitamin D levels (r = 0.010/ p  = 0.946), and mean right(r = -0.194/ p  = 0.178) and left (r = 0.061/ p  = 0.673) cIMT in the HD patients. Our study shows that sTWEAK levels are elevated in HD patients. This elevation has no association with the cIMT., Competing Interests: The authors declare they have no competing interests or conflicts of interest associated with this manuscript.The ethics committee at the Tabriz University of Medical Sciences reviewed and approved the present study, in compliance with the Declaration of Helsinki.Informed consent was obtained from all participants.

Statins, inhibitors of hydroxy methyl glutaryl coenzyme-A (HMG-CoA) reductase, are the most widely used drugs for treating hypercholesterolemia. However, statins can cause disabling myopathy as their main adverse effect. Several molecular mechanisms underlie the statin-induced myopathy including the decrease in the levels of essential mevalonate and cholesterol derivatives. This review discusses a further mechanism involving the loss of other anti-oxidant defenses besides ubiquinone (Co-Q) in skeletal muscles which produce a significant amount of reactive oxygen species (ROS). Therefore, to maintain their function, skeletal muscles need a high level of anti-oxidants.

Post-transplant ischemic acute kidney injury (AKI), secondary to ischemia reperfusion injury (IRI), is a major problem influencing on the short and long term graft and patient survival. Many molecular and cellular modifications are observed during IRI, for example, tissue damage result production of reactive oxygen species (ROS), cytokines, chemokines, and leukocytes recruitment which are activated by NF-κB (nuclear factor kappa B) signaling pathway. Therefore, inhibiting these processes can significantly protect renal parenchyma from tissue damage. Klotho protein, mainly produced in distal convoluted tubules (DCT), is an anti-senescence protein. There is increasing evidence to confirm a relationship between Klotho levels and renal allograft function. Many studies have also demonstrated that expression of the Klotho gene would be down regulated with IRI, so it will be used as an early biomarker for acute kidney injury after renal transplantation. Other studies suggest that Klotho may have a renoprotective effect for attenuating of kidney injury. In this review, we will discuss pathophysiology of IRI-induced acute kidney injury and its relation with klotho level in renal transplantation procedure., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Clinical and experimental studies have shown that mild traumatic brain injury (mTBI) is associated with increased anxiety- and depression-related behaviors and inflammation in the brain. Unfortunately, there are no specific therapies for long-term behavioral consequences of mTBI. This study set out to determine whether silymarin treatment compared to diazepam (DZP) and fluoxetine (FLX) can reduce neuroinflammation, anxiety- and depression-like behaviors after mTBI induction in mice. We used open field, elevated plus maze, light-dark box, zero maze, sucrose preference, forced swim, and tail suspension tests to assess anxiety and depression-like behaviors in mTBI-induced mice. The levels of tumor necrosis factor (TNF)-α protein, a marker of inflammation, in the prefrontal cortex and hippocampus was also measured. This study identified that the long-term treatment with DZP, FLX or SIL results in decreased anxiety and depression-like behaviors in mTBI-induced mice. The results also showed that these drugs reduced TNF-α levels in the prefrontal cortex and hippocampus. In addition, there were no significant differences between the effects of SIL and DZP or SIL and FLX on behavioral and cytokine levels in mTBI-induced mice. Our findings support the idea that mTBI could be a risk factor for anxiety- and depression-related disorders and neuroinflammation in the brain. Taken together, this study demonstrates that DZP, FLX or SIL can significantly reduce anxiety- and depression-like symptoms, and neuroinflammation after mTBI induction in mice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.

Background: Pregnancy Associated Osteoporosis (PAO) can lead to serious difficulties such as fragility fractures, elongated back pain and height loss in affected women. Soluble Receptor Activator of Nuclear Factor-Kappa B ligand (sRANKL) to Osteoprotegerin (OPG) ratio is chosen as a bone metabolism equation in many bone diseases characterized by bone resorption, such as post-menopausal osteoporosis and would be modified with folic acid supplementation. This study was done to compare the effects of high dose (5mg/day) and low dose (0.5 mg/day) folic acid in the RANKL/OPG ratio and Tumor Necrosis Factorα (TNFα) concentration during pregnancy., Methods: Forty-five pregnant women who visited the AL-Zahra Hospital, Tabriz Iran, from September 2013 to November 2014 were assigned into two groups in this randomized, double-blind, clinical trial, included women who took 5 mg/day (group1) and who took 0.5 mg/day (Group 2) folic acid supplementation before pregnancy until 36 th pregnancy. The biochemical variables in serum of pregnant women were measured before and at the end of the study. The study was registered in the Iranian Registry of Clinical Trials (IRCT) as ID, IRCT2013122315903N1., Results: OPG levels were significantly higher compared with the baseline value ( P =0.008), although sRANKL ( P <0.001), TNFα ( P =0.005) and sRANKL/OPG ratio ( P <0.001) reduced significantly with high dose of folic acid supplementation. A significant positive correlation was observed between the decreased RANKL and TNFα levels (r=0.451, P =0.031) at the end of study in high dose group., Conclusion: High dose of folic acid supplementation could decrease bone resorptive biomarkers and may prevent PAO in pregnant women by increasing OPG and decreasing sRANKL and TNFα.

Background: Scleroderma is a chronic connective tissue disease of unknown etiology. Vitamin D and parathyroid hormone (PTH) that play particular functions in calcium and phosphate homeostasis may be involved in the etiology of this disorder. Klotho, the co-receptor of the fibroblast growth factor 23 (FGF-23), can interfere with calcium and phosphate metabolism. The purpose of this study was to evaluate serum Klotho, FGF-23, intact PTH (iPTH) and vitamin D levels in scleroderma patients compared with the healthy controls., Methods: The study was performed in Biotechnology Research Center, Tabriz University of Medical Sciences (TUMS) from 2014-2015. Sixty scleroderma patients based on the classification criteria of systemic sclerosis and 30 age- and sex-matched healthy controls were included in this study. Serum Klotho, FGF-23, 25-hydroxy vitamin D (25-OH Vit D), and iPTH levels were analyzed using ELISA., Results: Serum levels of Klotho and 25-OH Vit D in the scleroderma patients were lower than those in the healthy controls ( P <0.001). In addition, scleroderma patients had higher serum iPTH levels than the controls ( P <0.001). There was no significant difference in serum FGF-23 levels between the patients and controls ( P =0.202)., Conclusion: The decreased serum Klotho, 25-OH Vit D, and increased iPTH levels in the scleroderma patients may be associated with the pathogenesis of this disease and could be considered a future therapeutic target.

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 extra-hepatic tissues, in particular intestine, adipose and cutaneous tissues in providing the cholesterol after reduction of the whole body cholesterol content by statins.

Intra-articular glucocorticoid (GC) injection has been used for more than half a century in the treatment of refractory synovitis in patients with rheumatoid arthritis (RA). There are limited data about the efficacy of intra-articular injection of various preparations of GCs on inflamed joint. The aim of this study was to compare the efficacy and side effects of intra-articular injection of dexamethasone (DEX) and triamcinolone hexacetonide (TH) in the treatment of knee joint arthritis in RA. In a double-blind randomized clinical trial, 70 patients with RA and knee joint arthritis were recruited to the study. Swelled knee joints were injected with 40 mg TH or 8 mg DEX randomly. The primary outcome measures were reduction of knee joint swelling and pain 1 and 3 weeks after joint injection. The secondary outcome measures were relapse of knee arthritis at 2, 4, and 6 months after injection and side effects of intra-articular injection. Difference in the knee circumferences between DEX and TH groups at weeks 1 and 3 was not significant. The average times of pain reduction after injection were 3.4 ± 2.3 and 2.3 ± 1.8 days in TH and DEX, respectively. There were no differences of knee pain between the two groups. Relapse of knee arthritis was occurred in two (6.7 %) and three (9.4 %) patients in the DEX and TH groups, respectively. Intra-articular injection of DEX like TH causes rapid and long-term reduction of knee pain and swelling in patients with RA and is safe.

Purpose: Klotho is a newly discovered protein that presumably has an important role in the aging process. The goal of this research is to compare the levels of Klotho and Endothelin-1 (ET-1) in the serum and aqueous humor of patients with pseudoexfoliation syndrome (PES) and pseudoexfoliative glaucoma (PEG)., Patients and Methods: Aqueous humor and serum samples were obtained at the time of cataract surgery from 15 patients with PES, 15 patients with PEG, and 15 control patients. All of the samples were analyzed using enzyme-linked immunosorbent assay to evaluate the levels of ET-1 and Klotho protein., Result: Aqueous and serum levels of Klotho in PES patients (49.02±10.97, 56.32±10.25 ng/mL) and PEG patients (34.53±4.87, 50.49±2.63 ng/mL) were lower than in control patients (56.31±7.68, 65.06±12.32 ng/mL). Both aqueous and serum levels of Klotho in the PEG group were lower than in the PES group (P=0.001). Mean aqueous and serum levels of ET-1 in the PES (1.28±0.09, 1.65±0.75 pg/mL) and the PEG groups (1.45±0.07, 1.58±0.58 pg/mL) were significantly higher than that measured in the control group (1.17±0.09, 1.16±0.34 pg/mL). Aqueous levels of ET-1 in the PEG group were higher than the PES group (P=0.04), but there were no significant difference in serum levels of ET-1 between the PES and the PEG groups (P=0.83)., Conclusions: Aqueous and serum levels of Klotho decreased both in PES and PEG patients, and this decrease in the PEG group was more significant. In contrast, aqueous and serum levels of ET-1 increased in the PES and the PEG patients, and the increase in the aqueous level of ET-1 in PEG patients was more significant.

Introduction: Calcineurin inhibitor nephrotoxicity is major problem after organ transplantation. It is multifactorial, but oxidative stress may have an important role in this process. It has been shown that angiotensin II receptor blockers have renoprotective effects but their molecular mechanism is largely unknown. Antioxidative effect is an important role of the recently known anti-aging protein, klotho. This study aimed to evaluate effect of valsartan in alleviation of cyclosporine A nephrotoxicity via a probable increase in serum klotho levels or decreasing oxidative stress., Materials and Methods: Thirty-two Sprague-Dawley rats were divided into 4 groups to receive 1 mL/kg/d of olive oil as control; 30 mg/kg/d of cyclosporine; 30 mg/kg/d of cyclosporine and 50 mg/kg/d of valsartan; and 50 mg/kg/d of valsartan. After the 6 weeks of administration period, serum levels of klotho and 8-hydroxydeoxyguanosine were measured using an enzyme-linked immunosorbent assay. Serum malondialdehyde level was measured spectrophotometrically., Results: The mean serum level of klotho was significantly lower in the cyclosporine group compared with control and valsartan groups. Klotho level in the valsartan group was significantly higher than those in the other groups. The cyclosporine group was detected to have significantly higher serum 8-hydroxydeoxyguanosine and malondialdehyde levels compared with the other study groups. The levels of klotho were negatively correlated with 8-hydroxydeoxyguanosine and malondialdehyde levels., Conclusions: Administration of valsartan may lead to attenuation of the nephrotoxic side effect of cyclosporine via enhancing klotho and decreasing oxidative stress levels.

Context and Objective: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH)., Design and Settings: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks., Results: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen., Conclusion: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

Unlabelled: Pre-eclampsia is a pregnancy-related multi-systemic hypertensive disorder and affects at least 5% of pregnancies. This randomized clinical trial aimed at assessing the effect of low doses and high doses of folic acid on homocysteine (Hcy) levels, blood pressure, urea, creatinine and neonatal outcome. A randomized clinical trial was done at Alzahra Teaching Hospital, Tabriz University of Medical Sciences from April 2008 to March 2013. Four-hundred and sixty nulliparous pregnant women were randomly assigned into two groups. Group 1 (n = 230) received 0.5 mg of folic acid and group 2 (n = 230) received 5 mg of folic acid per daily. They were followed until delivery. Blood pressure and laboratory changes, including plasma Hcy levels, were measured and compared between the groups. Homocysteine concentrations were significantly higher at the time of delivery in group 1 (13.17±3.89 μmol/l) than in group 2 (10.31±3.54, μmol/l) (p<0.001). No statistically significant differences were observed in systolic and diastolic blood pressure (p = 0.84 and 0.15, respectively). Birth weight was significantly higher in group 2 (p = 0.031) and early abortion was significantly higher in group 1 than group 2 (p = 0.001). This study has provided evidence that a high dosage of folic acid supplements throughout pregnancy reduces Hcy concentrations at the time of delivery., Trial Registration: Iranian Registry of Clinical Trials IRCT201402175283N9.

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 <0.05) higher plasma 8-OHdG, MDA, PCG, urea, and creatinine levels in comparison to other groups. Plasma urea and creatinine levels were negatively correlated with renal GPx expression and positively correlated with the oxidative stress markers. Conclusion: Administration of Val may result in attenuating the nephrotoxic side effect of CsA via probable renal GPx upregulation, and subsequently oxidative stress decrease.

To determine the concentration of inflammatory mediators in the tear film of patients with keratoconus. Basal tears from patients with keratoconus and from normal controls were collected using a capillary tube. Patients with keratoconus were examined in a routine fashion, and keratometric readings were also taken from corneal topographic maps .The concentration of cytokines including Interleukin 6,10,1b and Interferon-γ was measured by enzyme-linked immunoadsorbent assay. Seventy-two subjects were enrolled in the study including 42 patients with keratoconus and 30 normals. Patients with keratoconus had significantly higher levels of Interlukin 6,1b and Interferon-γ (17.49 ± 1.92 pg/ml), (8.58 ± 1.15 pg/ml), and (33.33 ± 7.57 pg/ml) compared with control subjects (13.81 ± 1.71 pg/ml), (4.98 ± 0.52 pg/ml), and (22.99 ± 4.68 pg/ml), (P = 0.0001, P = 0.0001, and P = 0.0001). But the level of Interlukin-10 in keratoconus patients was significantly lower (6.07 ± 1.35 pg/ml) than controls (8.99 ± 0.70 pg/ml) (P = 0.0001). We realized that the proinflammatory markers (Interlukin-6,1-b and Interferon-γ) are over expressed, whereas the anti-inflammatory marker (Interlukin-10) is under expressed, indicating that the pathogenesis of keratoconus may involve complex chronic inflammatory events. Additional future studies will reveal the exact molecular and biochemical mechanisms that are required to better manage the disease and halt its progression.

Aim: To evaluate the high sensitivity C-reactive protein (hsCRP), Fetuin-A and matrix γ-carboxyglutamate protein (MGP) as the main factors for vascular calcification and inflammation in serum of patients with advanced age-related macular degeneration (ARMD) in comparison to healthy controls., Methods: The subjects were 40 patients with choroidal neovascularization (CNV) having a mean age of 70.9±9.1y and a matched group of 49 apparently healthy control subjects. The ARMD was diagnosed using a slit-lamp with superfield lens, fundus photography and fluorescein angiography. Measurement of hsCRP was done by nephelometry method. Levels of Fetuin-A and MGP were measured by enzyme-linked immunosorbent assay (ELISA) technique., Results: hsCRP [0.45(0.07-2.63) mg/L vs 0.25(0.03-1.2) mg/L, P=0.02)] and Fetuin-A levels (50.27±5.04 vs 44.99±10.28 ng/mL, P=0.009) were higher in the patients than in the control groups. We could not find significant difference in MGP level between two groups (P=0.08). There was not a significant correlation between MGP with Fetuin-A and hsCRP among the patients (P=0.7, P=0.9 respectively). A significant negative correlation of hsCRP with Fetuin-A was observed in both case and control groups (P=0.004, r=-0.33 and P=0.001, r=-0.54, respectively)., Conclusion: Although our study shows that serum hsCRP and Fetuin-A is increased in CNV patients as well as negatively correlated with both study groups, their direct role on pathogenesis of ARMD required future studies.

Introduction: Plasma protein growth arrest-specific 6 (GAS6) and matrix Gla protein (MGP) are crucial mediators of vascular calcification and are involved in the development of vascular complications in chronic kidney diseases. This study was set out to investigate the relationship between plasma GAS6 levels and MGP in patients with end-stage renal disease on maintenance hemodialysis., Materials and Methods: Forty-six hemodialysis and 46 healthy individuals with normal kidneys were recruited. Plasma GAS6 and MGP concentrations and related biochemical factors were quantified as well as collection of data on clinical characteristics., Results: Plasma GAS6 levels were significantly higher in the hemodialysis patients as compared with the control group (763.52 ± 187.91 pg/mL versus 421.63 ± 189.91 pg/mL, P < .001). Plasma MGP concentration was significantly lower in the hemodialysis patients than the control group (52.35 ± 12.35 ng/mL versus 6.60 ± 19.54 ng/mL, P < .001). The levels of GAS6 were inversely associated with MGP (r = -0.341, P = .02) in the hemodialysis patients., Conclusions: Increased GAS6 and decreased MGP levels in hemodialysis patients, as mediators of induction or prevention of vascular calcification, and their inverse correlation may suggest that there might be a role in increased calcification process in hemodialysis patients or only as a secondary phenomenon of advanced kidney failure. Their direct role on vascular calcification needs further studies in the future.

Objective: To explore the probable association of serum hepcidin and haemoglobin levels with iron and inflammation statuses in patients of chronic kidney disease stage 4 with anaemia., Methods: The cross-sectional study was conducted at Tabriz University of Medical Sciences, Iran, from March 2011 to October 2012, and comprised patients of chronic kidney disease stage 4 with anaemia. Serum biochemical factors as well as hepcidin, ferritin, interleukin 6, high sensitivity C-reactive protein and iron levels were measured using standard methods. Statistical correlations were established using regression analysis and Pearson's correlation coefficient., Results: There were 40 patients among whom 15(37.5%) were males and 25(62.5%) were females with an overall mean age of 55.68±14.4 years. There was a significant inverse relationship between hepcidin and haemoglobin levels (p<0.05). There were significant correlations between hepcidin with iron status, nutritional and inflammatory markers such as ferritin, Total iron binding capacity, albumin and interleukin 6 (p<0.05 each)., Conclusions: Hepcidin had negative correlation with haemoglobin level in stage 4 chronic kidney disease patients with adequate iron stores, which could be effective in the development of anaemia in such patients.

Introduction: There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy., Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period., Results: Supplementation of the patients with FA for 36 week decreased the median (minimum- maximum) levels of serum Hcy from 11.40 μmol/L (4.40-28.70) to 9.70 (1.60-20.80) μmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms., Conclusion: Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women.

Introduction: Low fetuin-A and 1,25-hydroxyvitamin D3 (vitamin D) levels accompanied with high intact parathyroid hormone (PTH) contents are associated with cardiovascular disease in dialysis patients. The aim of present study was to evaluate the relationship between vitamin D receptor (VDR) gene FokI and ApaI polymorphisms with serum levels of fetuin-A, vitamin D, and intact PTH in hemodialysis patients., Materials and Methods: Serum was obtained from 46 stable chronic hemodialysis patients and 43 healthy controls. Serum levels of intact PTH, fetuin-A, vitamin D, calcium, and phosphorus were measured. Genotyping of the VDR gene was performed using standard methods., Results: Serum fetuin-A and vitamin D levels were significantly lower, whereas serum levels of PTH, calcium, and Phosphorus were higher in the hemodialysis patients than in the healthy controls. The FokI genotypes were more frequent in the hemodialysis patients than the control group (P = .004). With respect to FokI genotypes, intact PTH level was higher among the hemodialysis patients compared to the controls (P = .02). In contrast, vitamin D level was lower in the hemodialysis patients with ApaI genotypes compared to the control group (P = .04)., Conclusions: Our study shows that increased serum level of PTH and decreased fetuin-A and vitamin D levels may increase susceptibility of atherosclerosis in patients with hemodialysis through VDR gene FokI and ApaI polymorphisms.

Oxidative stress plays a crucial role in the pathogenesis of multiple sclerosis (MS). Previous studies have shown that oxidative stress is one of the main underlying mechanisms of arsenic-induced cellular damage. The aim of this study was to assess the serum levels of arsenic and its relationship with lipid peroxidation in MS patients from Tabriz, as the third polluted city of Iran. The study population included 38 MS female patients and 38 age-matched healthy controls. Serum malondialdehyde (MDA) and arsenic levels were measured using thiobarbituric acid reactive substances (TBARS) assay and electrothermal atomic absorption spectrometry, respectively. The results showed that the arsenic (P < 0.01) and MDA (P = 0.03) levels were significantly higher in patients with MS than those in control. Moreover, serum levels of arsenic and MDA were positively correlated in MS patients. The elevated levels of serum arsenic might explain the increased oxidative stress in MS patients. We suggest that high arsenic levels in serum may lead to MS development, and therefore, exposure to this metal should be limited.