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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.

Cisplatin is a therapeutic drug widely used to treat various solid tumors. Nephrotoxicity is a well-known side effect in patients treated with cisplatin. Falcarindiol (FAD), natural polyacetylene compound greatly found in Apiaceae family, has anti-cancer, -bacterial, -inflammatory and -oxidant activity which is utilized in the present study. Thirty male C57BL/6 mice were randomly divided into five groups of six each; sham, cisplatin (15 mg/kg), cisplatin + FAD (50 and 100 mg/kg/day), and FAD (100 mg/kg/day). Cisplatin administration elevated the concentrations of BUN and creatinine, as well as kidney histopathologic damage. On the other hand, FAD treatment attenuated cisplatin-induced injury, and also down-regulated mRNA levels of TNF-α and IL-1β together with protein expression of p-NF-kB p65. Moreover, FAD induced the protein expression of p-AMPK and nuclear Nrf2 accompanied by its respective target genes such as NQO-1 and HO-1 in a dose-dependent manner. In conclusion, the findings collectively characterize FAD as a drug candidate to treat cisplatin-induced nephrotoxicity thorough down-regulation of NF-kB signaling pathway in mice

Introduction: Doxorubicin (DOX) is one of the most common drugs in cancer treatment. However, its partial solubility along with the high incidence of side effects remains a challenge to tackle. To address these issues, we designed a formulation based on graphene oxide (GO) and used it as an anticancer drug delivery system. Methods: The physical and chemical properties of the formulation were studied using FTIR, SEM, EDX, Mapping, and XRD. Release studies in the in vitro condition were used to evaluate the pH sensitivity of drug release from nanocarriers. Other in vitro studies, including uptake assay, MTT, and apoptosis assay were carried out on the osteosarcoma (cell line. Results: In vitro release studies confirmed that the synthesized formulation provides a better payload release profile in acidic conditions, which is usually the case in the tumor site. On the OS cell line, the cytotoxicity of the DOX-loaded nanocarrier (IC50=0.293 μg/mL) and early apoptosis rate (33.80 % ) were higher in comparison to free DOX (IC50=0.472 μg/mL, and early apoptosis rate= 8.31 % ) after 48 hours. Conclusion: In summary, our results suggest a DOX-loaded graphene oxide carrier as a potential platform for targeting cancer cells.

Objectives Palindromic rheumatism (PR) is characterized by repetitive, afebrile episodes of acute arthritis and peri-arthritis. The aim of this study was considering the long-term outcomes of patients with PR who were treated with tight control strategy using Disease-modifying anti-rheumatic drugs (DMARDs). Methods We reviewed the charts of 106 patients diagnosed with PR who were referred to the Connective Tissue Diseases Research Center (CTDRC). We recruited all the patients diagnosed with PR according to the criteria of Hannonen. They visited the CTDRC clinic regularly and were treated with hydroxychloroquine and low dose prednisolone because of active episodes of PR. In cases that the attacks did not come under control in 3–6 months, methotrexate was added or replaced and the dose was increased up to 25 mg/week. In resistant cases, sulfasalazine was added, followed by the addition of leflunomide and then azathioprine. Disease outcome was evaluated by getting complete or partial remission and prevention of disease evolution to rheumatoid arthritis (RA) or other inflammatory connective tissue diseases. Results This study included 92 patients with PR who were treated with DMARDs. Attacks were controlled completely or partially in 76 (82.6%) patients. Medications free remission was obtained in 16.3% of the patients. RA developed in 8.7% of the patients. By multivariate logistic regression analysis, age ≤40 at disease presentation, non-adherence to therapy and PIP joints involvement were the only factors which independently predicted the risk of treatment failure. Conclusions Tight control strategy by using DMARDs may control PR and prevent disease progression to RA.

Background/aim: This study aimed to evaluate the demographic, clinical, angiographic and prognostic characteristics of Takayasu arteritis TA in Iran. Materials and methods: A total of 75 patients with TA based on the American College of Rheumatology 1990 criteria for TA classification referred to the Rheumatology Centres, were followed-up from 1989 to 2019. Demographic, clinical, angiographic and prognostic characteristics were collected at baseline and last visit. Results: The mean age was 31.9 ± 9.8 years at the disease onset. Female to male ratio was 14. The median latency in diagnosis was 24 months. Pulse discrepancy in the arms, blood pressure discrepancy in the arms, limb claudication, hypertension and constitutional symptoms were the most common clinical features. The most common angiographic type at the time of diagnosis was Type I 42.7% . The most frequent arterial lesion was stenosis 89.4% . Subclavian, carotid and aortic arteries were the most commonly involved arteries. New lesions developed in 28.6% of patients during the 5.25-year follow-up. Vasculitis-induced chronic damage was observed in all patients. Disease activity decreased and vascular damage remained stable throughout the follow-up period. Conclusions: The clinical features and angiographic type of TA in Iran are different from most Asian countries. Differences in angiographic and clinical features may lead to delayed diagnosis. The issue of delay in diagnosis should create awareness among health care providers that TA is not a very rare disease in Iranians and failure to pay attention to warning symptoms may delay the diagnosis.

Aim of the work: 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. Patients and methods: 44 RA patients and 44 matched controls were studied. Disease activity score (DAS-28) was assessed. Serum TLR4, 8-OHdG and TAC were measured. Results: 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

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.

The presence of inflammatory cells and their products in the tumor microenvironment plays a crucial role in the pathogenesis of a tumor. Releasing the cytokines from a host in response to infection and inflammation can inhibit tumor growth and progression. However, tumor cells can also respond to the host cytokines with increasing the growth/invasion/metastasis. Bladder cancer (BC) is one of the most common cancers in the world. The microenvironment of a bladder tumor has been indicated to be rich in growth factors/inflammatory cytokines that can induce the tumor growth/progression and also suppress the immune system. On the contrary, modulate of the cancer progression has been shown following upregulation of the cytokines-related pathways that suggested the cytokines as potential therapeutic targets. In this study, we provide a summary of cytokines that are involved in BC formation/regression with both inflammatory and anti-inflammatory properties. A more accurate understanding of tumor microenvironment creates favorable conditions for cytokines targeting to treat BC.

Receptor for advanced glycation end-products (RAGE) is involved in the pathogenesis of diabetic nephropathy. FPS-ZM1, a selective RAGE inhibitor, in combination with valsartan were investigated for their protective potentials on the renal markers of tubular injury in streptozotocin-induced diabetic rats. Rats were assigned into groups of receiving FPS-ZM1 (1 mg/kg/day), valsartan (100 mg/kg/day), and FPS-ZM1 plus valsartan (1 mg/kg/day and 100 mg/kg/day, respectively) for one month. Kidney histology, renal inflammation and oxidative stress, and renal and urinary markers of tubular injury were investigated. FPS-ZM1 and valsartan in combination more significantly attenuated renal expressions of tumor necrosis factor-alpha and interleukin-6 genes and reduced urinary levels of interleukin-6. Moreover, the combination elevated renal NAD+/NADH ratios and Sirt1 activities, and mitigated nuclear acetylated NF-κB p65 levels. In addition to alleviating indices of oxidative stress i.e. malondialdehyde, superoxide dismutase and glutathione peroxidase, the combination of FPS-ZM1 and valsartan more effectively upregulated the renal levels of master antioxidant proteins Nrf2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase-1. Additionally, this dual therapy ameliorated more efficiently the indices of renal tubular injuries as indicated by decreased renal kidney injury molecule-1 levels as well as reduced urinary levels of cystatin C, retinol binding protein, and beta-2-microglobulin. While FPS-ZM1 alone had no appreciable effects on the renal fibrosis, the combination treatment ameliorated fibrosis better than valsartan in the kidneys. Collectively, these findings underline the extra benefits of FPS-ZM1 and valsartan dual administrations in obviating the renal tubular cell injury in streptozotocin-induced diabetic rats partly by suppressing renal inflammation and oxidative stress.

Survivin which is an inhibitor of apoptosis upregulation has been reported in human autoimmune diseases including rheumatoid arthritis, psoriasis, juvenile idiopathic arthritis and systemic sclerosis, and mouse models of systemic lupus erythematosus. Survivin in systemic lupus erythematosus is downregulated. However, there is no significant association between serum survivin levels and clinical characteristics of SLE.

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 Altered innate immune function plays an important role in the initiation of inflammatory response in Behcet's disease (BD). Toll-like receptors (TLRs) are the master regulators of the innate immune system. Because the role of TLRs remains unknown in the pathogenesis of BD, the present study aimed to evaluate the expression levels and methylation status of the TLR2 and TLR4 promoters in patients with BD. Methods In the present study, Iranian Azeri BD patients (n = 47) with an active (n = 22) and inactive (n = 25) period, and healthy controls (n = 61), were matched according to age, sex and ethnicity. TLR2 and TLR4 genes promoter CpG islands were predicted with the Eukaryotic Promoter Database (https://epd.vital-it.ch). Methylated DNA immunoprecipitation (MeDIP) was conducted. Results The results showed that mRNA of TLR4 was significantly increased in the peripheral blood mononuclear cells (PBMCs) of BD patients with an active phase compared to the control group. Differences in mRNA of TLR4 between the inactive BD and control groups were not significant. Differences in TLR2 mRNA levels in the PBMCs of the active and inactive phase BD and control groups were not significant. The methylation rate of TLR4 gene promoter was significantly lower in the active and inactive BD groups compared to the control group. The difference between the active and inactive BD groups was not significant. There was no significant difference in the methylation rates of the TLR2 gene between studied groups. Conclusions Our preliminary findings suggest that the hypomethylation of TLR4 gene may be involved in the pathogenesis of BD via increasing TLR4 expression.

Inflammation plays a significant role in the pathogenesis of chronic diseases. Inflammatory diseases such as bacterial diseases, Alzheimer's disease, rheumatoid arthritis, multiple sclerosis, and so on, impose huge costs on the health systems. On the other hand, some side effects have been reported for the classic drugs used to treat these diseases. Plants phytochemicals have revealed important prospects in the handling and controlling of human diseases. β-lapachone, is a derivative of the naturally occurring element lapachol, from Tabebuia avellanedae and its anti-inflammatory effects have been reported in several reports. This review summarized the evidence from cell and animal studies supporting the anti-inflammatory role of β-lapachone and discussed its potential mechanisms.

ObjectiveThis study assessed the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume, platelet distribution width, and red cell distribution width (RDW) in systemic lupus erythematosus (SLE) patients and their correlation with disease activity.MethodsTwo hundred eight SLE patients and 205 age- and sex-matched healthy controls were included. Disease activity was assessed using the systemic lupus erythematosus disease activity index 2000, and hematological indices were determined.ResultsLymphocyte and platelet counts were significantly lower in SLE patients than in the controls, while the NLR, PLR, and RDW were significantly higher (P < .05). In patients with active disease, the neutrophil counts, NLR, and PLR were significantly higher than in those with inactive disease (P < .05), while the lymphocyte count was significantly lower (P < .05). Based on receiver operating characteristic curve analyses, only for lymphocyte count and PLR. The area under curve was significantly higher (P = .001 and P = .053, respectively).ConclusionPLR can serve as a biomarker for indicating SLE disease activity.

Bladder cancer is one of the most prevalent genitourinary cancers responsible for about 150,000 deaths per year worldwide. Currently, several treatments, such as endoscopic and open surgery, appended by local or systemic immunotherapy, chemotherapy, and radiotherapy are used to treat this malignancy. However, the differences in treatment outcome among patients suffering from bladder cancer are considered as one of the important challenges. In recent years, cancer stem cells, representing a population of undifferentiated cells with stem-cell like properties, have been eyed as a major culprit for the high recurrence rate in superficial papillary bladder cancer. Cancer stem cells have been reported to be resistant to conventional treatments, such as chemotherapy, radiation, and immunotherapy, which induce selective pressure on tumoral populations resulting in selection and growth of the resistant cells. Therefore, targeting the therapeutic aspects of cancer stem cells in bladder cancer may be promising. In this study, we briefly discuss the biology of bladder cancer and then address the possible relationship between molecular biology of bladder cancer and cancer stem cells. Subsequently, the mechanisms of resistance applied by cancer stem cells against the conventional therapeutic tools, especially chemotherapy, are discussed. Moreover, by emphasizing the biomarkers described for cancer stem cells in bladder cancer, we have provided, described, and proposed targets on cancer stem cells for therapeutic interventions and, finally, reviewed some immunotargeting strategies against bladder cancer stem cells.

Objective: Behcet's disease (BD) is an inflammatory disease and smoking may have a role in its triggering. This case-control study was conducted to investigate the association between smoking and the risk of BD. Methods: We included 192 patients with BD and 822 healthy siblings of patient with BD and 373 healthy unrelated persons as control groups. Demographic data and smoking history of patients and their siblings were obtained by direct and in some cases by telephone interview with the participants. Demographic data and smoking history of healthy controls were obtained by direct interview. Propensity score matching (PSM) analyses for reducing the heterogeneity between studied groups and calculating the actual effect of smoking in BD was performed. Matching was performed based on demographic characteristics (age, gender, educational status and marital status). After PSM, we carried out multivariate analyses with BD as the main outcome variable and smoking history as the main predictor variable to calculate odds ratios with 95% confidence intervals. Results: Ever smoking was not significantly associated with an increased risk of BD compared with never smoking. In comparison with healthy siblings and healthy unrelated persons, the relative risk of developing BD was 0.8-2.6. No significant differences were observed in the clinical manifestations of BD patients in ever smokers and never smokers. However, disease activity in ever smokers at disease presentation was significantly more than never smokers. Conclusion: Smoking is not a significant risk factor for BD.

Summary Aim: Atherosclerotic lesions in the carotid arteries lead to a broad range of cerebrovascular disorders such as vascular dementia and ischaemic stroke. Recent studies have verified the beneficial role of atorvastatin (AV) in atherosclerosis. Despite a large body of studies, the mechanisms underlying this effect have not been completely explained. In this study, several experiments were performed on atherosclerotic rat models to investigate the anti-inflammatory and anti-apoptotic effect of AV in the carotid artery. Methods: In this experimental study, 40 male Wistar rats (250 ± 25 g) were randomly divided into four groups: rats on a normal diet (ND; n = 10); a high-cholesterol diet (HD; n = 10); a high-cholesterol diet plus AV (HD + AV; n = 10); and the AV control group (AV; n = 10). Cleavage of caspase-3 protein, expression of B-cell lymphoma 2 (Bcl-2) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) were determined by immunoblotting assay in the carotid artery homogenate. Plasma atherogenic indices, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured by colorimetric assay at the end of the experiment. Plasma levels of oxidised LDL (oxLDL) were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Results: After eight weeks of feeding with a high-cholesterol diet, an elevated level of oxLDL was observed in the plasma in the HD group compared with the ND group [214.42 ± 17.46 vs 69.13 ± 9.92 mg/dl (5.55 ± 0.45 vs 1.78 ± 0.26 mmol/l); p < 0.01]. AV administration significantly reduced oxLDL levels in the HD + AV compared to the HD group [126.52 ± 9.46 vs 214.42 ± 17.46 mg/dl (3.28 ± 0.25 vs 5.55 ± 0.45 mmol/l); p < 0.01]. Results also showed that compared with the HC group, the HC + AV group had lower levels of p38 phosphorylation (p < 0.05) and higher levels of Bcl-2 expression (p < 0.05). Lower levels of cleaved caspase-3 were observed in the HC + AV group in comparison with the HC group (p < 0.05). Conclusions: The resultant data suggest that the anti-apoptotic effect of AV could be partially mediated by the pro-inflammatory protein p38 MAPK and the anti-apoptotic protein Bcl-2 in the rat carotid artery. Atorvastatin can therefore be considered a target drug in the prevention or development of atherosclerotic events.

Background: Rheumatoid arthritis (RA) is one of most important collagen vascular diseases. It has an unknown origin. Objectives: The aim of this study was to evaluate circulating levels of osteoprotegerin (OPG), total soluble receptor activator of nuclear factor-Kappa B ligand (total sRANKL), and OPG/RANKL ratio in patients with RA. Methods: Forty-five females with RA, who fulfilled the American college of rheumatology (ACR) criteria for RA were included in this cross-sectional study. The overall disease activity was evaluated by the disease activity score based on 28 joint counts (DAS-28). The OPG and sRANKL were measured by the enzyme-linked immunosorbent assays (ELISA). The levels of high sensitive C-reactive protein (hsCRP) were measured by ELISA. We used Pearson's correlation for our comparisons. Results: There was no statistically significant dierence between the levels of hsCRP, OPG, sRANKL and RANKL/OPG ratio in terms of DAS; 28 grades in our patients.No significant correlation was found between the serum levels of OPG and DAS-28 (P = 0.525), duration of the disease (P = 0.884), Z score of the femur (P = 0.546) and Z score of the spine (P = 0.492), T score of the femur (P = 0.137) and T score of the spine (P = 0.821) in the patient group. No significant correlations were found between sRANKL levels with DAS-28 (0.919), Z score of the femur (P = 0.971), Z score of the spine (P = 0.832) and T score of the femur (P = 0170) in the studied groups. Conclusions: Our study showed that there was no significant correlation between hsCRP, OPG, sRANKL and RANKL/OPG ratio in DAS-28 grading of our patients. For this reason they will not be used for evaluating disease activity. However, there was a significant dierence between case and control groups except for sRANKL (pg/mL).

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.

Resistance to chemotherapy with 5-fluorouracil (5-FU) in patients with colorectal cancer (CRC) is the major obstacle to reach the maximum efficiency of CRC treatment. Combination therapy has emerged as a novel anticancer strategy. The present study evaluates the cotreatment of γ-tocopherol and 5-FU in enhancing the efficacy of chemotherapy against HT-29 colon cancer cells. Cytotoxic effect of this combination was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and a synergistic effect was evaluated by a combination index technique. Nuclear morphology was studied via 4',6-diamidino-2-phenylindole staining and flow cytometric assays were conducted to identify molecular mechanisms of apoptosis and cell cycle progression. We investigated the expression of Cyclin D1, Cyclin E, Bax, and Bcl-2 by a quantitative real-time polymerase chain reaction. The IC50 values for 5-FU and γ-tocopherol were 21.8 ± 2.5 and 14.4 ± 2.6 μM, respectively, and also this combination therapeutic increased the percentage of apoptotic cells from 35% ± 2% to 40% ± 4% (P

Introduction: Immune responses and inflammation are major risk factors for mortality in patients with end-stage renal disease (ESRD). Increased oxidative stress is a common feature of ESRD, and it has been speculated that it is interrelated to inflammation. In many studies it has been proved that red grape seed extract (RGSE) provides an antioxidant efficacy. Objectives: The aim of this study was to investigate the anti-inflammatory effects of RGSE in hemodialysis patients. Patients and Methods: Thirty hemodialysis individuals were divided into two groups that received either 200 mg/day of the RGSE or placebo for one month. Mean ± SD of age of patients was 58.5 ± 10.5 years. Duration of dialysis was 4 ± 3.4 years and 27 patients were male and 3 patients were female. After a 2-week washout period, the groups were crossed over for another one month. Markers of inflammation, lipid profiles and blood factors were measured at baseline after intervention with RGSE or placebo. Results: Our results showed that RGSE consumption could not make statistically significant changes in markers of inflammation, lipid profiles and blood factors in hemodialysis patients. Conclusion: Although RGSE could not improve markers of inflammation, lipid profiles and blood factors in hemodialysis subjects over a 1 month period. However, this result may be due to short period of treatment or low dose of RGSE. Further studies need to clear these contradictions

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

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.

Drug delivery for successful treatment of cancer, which is potently facilitated by progress in nanotechnology opens new avenue in this field. Graphene oxide (GO) and its derivatives, as the most investigated and used delivery system, have various potential characteristics make it a suitable candidate for cancer treatment. Increased loading capacity, enhanced surface area, capability of reactive oxygen species induction, as well as aptitude for surface functionalization are among the most important features of these nanoparticle. An accumulating body of recent studies have been reported the high efficacy of GO and its derivatives in cancer biosensing, gene delivery, drug delivery, photothermal therapy, combination therapy, and concurrent therapy and diagnostics (theranostics). Therefore, the present review is aimed to elaborate the critical function of GO and its derivatives in cancer diagnosis and therapy.

Oxidative stress and neuroinflammation are critically involved in amyloid beta (Aβ) induced cognitive impairments. β-Lapachone (β-LAP) is a natural activator of NAD(P)H quinone oxidoreductase 1 (NQO1) which has antioxidant and anti-inflammatory properties. This study investigated the effect of β-LAP administration on Aβ-induced memory deficit, oxidative stress, neuroinflammation, and apoptosis cell death in the hippocampus. Forty BALB/c mice were allocated into control, sham, β-LAP (βL), Aβ, and Aβ + βL groups. Intracerebroventricular injection of Aβ1-42 was used to induce Alzheimer’s disease (AD) model. Mice in the βL and Aβ + βL groups were treated with β-LAP (10 mg/kg, i.p) for 4 days. Results revealed that β-LAP attenuated memory impairment in the Aβ-received mice, as measured in the novel object recognition (NOR) and Barnes maze tests. Moreover, Aβ resulted in inflammasome activation evident by enhanced caspase-1 immunoreactivity and interleukin-1 beta (IL-1β) protein levels. However, β-LAP could markedly reduce reactive oxygen species (ROS) production and down-regulate mRNA expression of NLRP3 inflammasome and protein levels of cleaved caspase 1 and IL-1β. Additionally, β-LAP-treated mice showed increased SIRT1 levels and NAD+/NADH ratio in the hippocampus. These results were followed by fewer number of TUNEL-positive cell, reduced hippocampal atrophy and neuronal loss in the hippocampal dentate gyrus (DG). These results indicated that the protective effect of β-LAP against AD-associated cognitive deficits is partially through its strong antioxidant and anti-inflammatory actions.

Empagliflozin, a SGLT-2 inhibitor, improves diabetic nephropathy through its pleiotropic anti-inflammatory effects. The present study aims to evaluate empagliflozin effects on renal and urinary levels of tubular epithelial cell injury markers in streptozotocin-induced diabetic rats. Empagliflozin at 10 mg/kg (p.o.) was administered for 4 weeks, beginning 8 weeks after induction of diabetes. Renal function as well as markers of renal tubular epithelial cell injury were assessed in kidney tissue homogenates and urine. Empagliflozin was able to ameliorate diabetes induced elevations in serum cystatin C levels. It also alleviated renal KIM-1/NGAL levels and urinary albumin, α-GST, and RBP excretions. In addition to decreasing urinary levels of cell cycle arrest indices i.e. TIMP-2 and IGFBP7, empagliflozin mitigated acetylated NF-κB levels in renal tissues of diabetic rats. As a whole, these findings reveal empagliflozin capability in improving diabetic nephropathy via ameliorating indices of renal inflammation, injury, and cell cycle arrest on streptozotocin-induced diabetic rats.

Introduction: This study aimed to discover by which mechanism selenium (Se) suppresses stimulated platelets stimulation in oxidative stress underlying diseases. Methods: Human platelets pretreated with Se and stimulated by Cu2+-oxidized low density of lipoprotein (OxLDL) or thrombin before assessment of P-selectin and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), phosphorylated Jun N-terminal kinase (p–JNK), and phosphorylated extracellular signal-regulated kinases (p-ERK1/2). All variables were measured by solid phase sandwich enzyme-linked immunosorbent assay (ELISA). Results: Se significantly decreased Cu2+-OxLDL induced P-selectin expression, as well as p38 and JNK phosphorylation in platelets, but could not significantly reduce ERK1/2 phosphorylation. Conclusion: Se suppresses inflamed platelets. This effect maybe partly mediated by the p38 or c-JNK signaling pathways. These results create possibility of new co-anti-inflammatory insight for Se in atherosclerosis.

Background Recurrent aphthous stomatitis (RAS) is characterized by recurrent, painful, shallow, round or oval oral ulcers surrounded by inflammatory halos. Aim of the work To investigate the status of vitamin D in RAS patients and the relationship between vitamin D levels and the severity of RAS. Patients and methods In this cross sectional study 46 patients with idiopathic minor RAS (MIRAS), and 49 age and sex matched healthy controls were included. Patients with at least 3 minor aphthous oral ulcers in a year without any known cause for RAS were determined as idiopathic minor recurrent aphthous stomatitis. The severity of RAS was assessed by the number of oral aphthous ulcers in each attack and the frequency of attacks. 25-Hydroxy vitamin D [25(OH) D] levels were measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method in patients and control groups. Results The mean 25(OH) D level in the MIRAS group was lower than the control group (12.1 ± 7.7 ng/dl vs. 27.4 ± 9.7 ng/dl, p = 0.0001). Insufficiency and deficiency of 25(OH) D in the recurrent aphthous stomatitis groups were more common than those in the control group (Vitamin D sufficient, Vitamin D insufficient and Vitamin D deficient (p

Objective: Pentraxin 3 (PTX3) and C-reactive protein (CRP) may be associated with development of diabetic vascular complications. In the current study we evaluated the relationship between PTX3 levels and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). Furthermore, we compared the sensitivity and specificity of PTX3 and CRP for detection of CAD. Methods: In 275 T2DM patients, coronary angiography revealed CAD (stenosis ≥ 50% at least in one vessel) in 140 patients and 135 patients without CAD. Gensini score was used to assess the severity of CAD. Demographic parameters and biochemical characteristics were measured in all participants. Results: Log-transformed mean plasma PTX3 levels were higher in T2DM patients with CAD than in T2DM patients without CAD (2.42 ng/mL vs 1.98 ng/mL, p

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.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.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.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.

The circulating anucleated platelets are involved in pathophysiology of several cerebrovascular diseases (CVD) such as atherosclerosis, Alzheimer and stroke. Platelets should be activated before involving in the inflammatory or hemostatic events. Oxidized low density lipoprotein (oxLDL) as oxidative stress inducer and one of the major risk factors in atherosclerosis leads to vast changes in platelets proteome. The objective here is to study proteins involved in such phenomena. In the current study, quiescent human platelets activated by oxLDL.2D SDS-PAGE (pH 3-10) were used to separate platelet proteins. Progenesis SameSpots statistical software was used to compare the gel images of resting and activated platelets with each other. Finally, comparatively expressed proteins were identified using Matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF) mass spectroscopy technique (MALDI-TOF MS). This study showed altered levels of actin binding proteins such as myosin-9, Cofilin-1 and transgelin2. It has also pointed to overexpression of Thrombospondin (TSP)-1, Fibrinogen, Proto-oncogene tyrosine-protein kinase Src, and underexpression of Enoyl-CoA hydratase, mitochondrial, Ubiquitin-like modifier-activating enzyme 7. Alteration in actin associated protein hints towards the cytoskeletal changes necessary to oxidative stress effect on platelets. Additionally, altered expression levels of Thrombospondin (TSP)-1and Proto-oncogene tyrosine-protein kinase following oxidative stress signifies that cerebrovascular events can partly modulate via Src kinase pathway or/and TSP- TNF?- TLR4/NF-Kb pathway. These findings can raise our basic knowledge about platelet function and novel drug targets, leading to the discovery of the mechanism(s) of action of new antiplatelet drugs.

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.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.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).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.