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Background: Early detection of breast cancer (BC) is extremely important as late diagnosis has been associated with a high rate of mortality. Immunogenic proteins and autoantibodies have been considered as favorable targets for early detection and targeted therapy in cancer. Accordingly, the present study aimed to identify the immunogenic antigens in both early and advanced stages of BC via a serologic proteome analysis (SERPA) approach. Method: This is a case-control study wherein we separated the proteins from BC tissues in the early stages (n = 10) and advanced stages (n = 10) utilizing two-dimensional electrophoresis (2DE) and then transferred them onto a Polyvinylidene Difluoride (PVDF) membrane. To explore the tumor antigens reacting with antibodies, two-dimensional (2D) blots of tumor tissues in the early and advanced stages were separately probed with the sera from the same patients. Afterwards, we identified antibody-reactive proteins via liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results: Fibrinogen beta chain (FGB), protein deglycase DJ-1(PARK7), and peroxiredoxin-2 (PRDX2) were the highly reactive antigens identified in the earlystage patients. In addition, RuvB-like1 (RUVBL1) and triose phosphate isomerase (TPI) were recognized as the immune reactive proteins in the late-stage patients. Conclusion: The results herein revealed that the immune-proteome pattern of BC patients changes along with tumor progression from primary to advanced stages. Moreover, immunogenic proteins seemed to stimulate the humoral immune system to produce autoantibodies in the initiation phase of BC; these autoantibodies could be employed as complementary factors for early detection of BC. The findings are however preliminary, and further studies with a larger sample size are required for verification and validation of previous findings. [ABSTRACT FROM AUTHOR]

Introduction: Oral lichen planus (OLP) is a chronic mucocutaneous inflammatory disorder with an unknown etiology. Although a considerable body of evidence suggests that immunologic factors are involved in the etiology of OLP, the involvement of cytokines in the pathogenesis of the disease is not fully understood yet. The aim of the present study was to assess interleukin-6 (IL-6) levels as a proinflammatory cytokine in the saliva of OLP patients compared to healthy controls. Materials & Methods: This case-control study was conducted on 30 OLP patients (12 males and 18 females) and 30 healthy control subjects, selected from individuals who were referred to the Department of Oral and Maxillofacial Diseases in Faculty of Dentistry, Babol University of Medical Sciences. Samples of unstimulated saliva were collected. Salivary IL-6 levels were measured using an ELISA kit and compared between OLP patients and healthy controls. The collected data were analyzed by Chi-square, independent t-test, and receiver operating characteristic (ROC) curve using SPSS 18 Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated. A value of p<0.05 was considered significant. Results: Mean salivary IL-6 values in OLP patients and healthy controls were 24.68±9.90 ng/L and 13.76±9.27 ng/L, respectively. The difference was statistically significant (P<0.001). The mean IL-6 values in reticular and erosive forms of OLP clinically were 24.35±9.26 ng/L and 24.91±10.64 ng/L, respectively. This difference was not statistically significant (P=0.87). Conclusion: Higher levels of IL-6 in saliva of OLP patients compared with healthy controls support the role of IL-6 in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Objective: In this study, the impact of arbutin was examined in a gentamicin (GM)-induced nephrotoxicity model. Materials and Methods: Forty adult male Wistar rats were randomly assigned to five groups including control group; GM group, and three groups of GM+arbutin (25, 50 and 75 mg/kg). One day after the last injection of GM, creatinine, urea, carbonyl, thiobarbituric acid-reacting substance (TBARs), ferric reducing antioxidant power (FRAP) and 8-hydroxyguanosine levels were assessed in serum samples. Left and right kidneys were used for biochemical assays and histological evaluation, respectively. Results: Our data showed that the FRAP level (p<0.05), urea (p<0.001), creatinine (p<0.001), and 8-hydroxyguanosine (p<0.001) levels of serum samples, were increased in GM-treated rats compared to the controls. The serum levels of TBARS (p<0.001) and carbonyl increased in serum and renal tissue (p<0.001) of GM-treated animals. Conversely, arbutin attenuated serum creatinine, urea and 8-hydroxyguanosine, and TBARS (p<0.001). Administration of arbutin significantly decreased carbonyl levels in serum and renal tissue samples (p<0.001). Furthermore, the levels of FRAP increased in the serum (p<0.01) and renal tissue samples (p<0.001) of arbutin-treated animals. Histological staining showed that arbutin significantly inhibits kidney damages. Conclusion: Our data suggest that arbutin attenuates GM-induced nephrotoxicity through its free radicals-scavenging activity. [ABSTRACT FROM AUTHOR]

Objective: Arbutin (p-hydroxyphenyl-β-D-glucopyranoside) possesses beneficial functions including antioxidant, antiinflammatory, and anti-tumoral activities. Due to the important role of oxidative stress and apoptosis in the successful treatment of cancer, understanding mechanisms that lead to apoptosis in cancer cells, is essential. The purpose of the current study was to evaluate the effect of arbutin on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress and the related mechanisms in fibroblast and Lymph Node Carcinoma of the Prostate (LNCaP) cells. Materials and Methods: In this experimental study, the LNCaP and fibroblast cell lines were pre-treated with arbutin (50, 250 and 1000 μM). After 24 hours, t-BHP (30 and 35 μM) was added to the cells. Viability was measured (at 24 and 48 hours) using MTT assay. The antioxidant effect of arbutin was measured by FRAP assay. The mRNA expression of P53 and BAX/BCL-2 ratio were measured using quantitative polymerase chain reaction (PCR). The percentage of apoptotic or necrotic cells was determined using a double staining annexin V fluorescein isothiocyanate (FITC) apoptosis detection kit. Results: Arbutin pre-treatment increased the total antioxidative power and cell viability in the MTT assay and reduced BAX/BCL-2 ratio, P53 mRNA expression and necrosis in fibroblasts exposed to the oxidative agent (P<0.001). In addition, our results showed that arbutin can decrease cell viability, induce apoptosis and increase BAX/BCL-2 ratio in LNCaP cells at some specific concentrations (P<0.001). Conclusion: Arbutin as a potential functional β-D-glucopyranoside has strong ability to selectively protect fibroblasts against t-BHP-induced cell damage and induce apoptosis in LNCaP cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: The age-related autoinflammation-mediated atherosclerosis is associated with some immunological, nutritional, and metabolic parameters and redox status. Here, we evaluated the association of circulatory interleukin 10 (IL-10) levels with lipid profile, some nutrients, and total anti-oxidant capacity in elderly people who presented cardiovascular disease (CVD) with or without metabolic syndrome (MetS) and in healthy subjects. METHODS: In this cross-sectional case-control study, 258 sera prepared from elderly people (144 healthy and 114 patient subjects) who participated in a community-based study, the Amirkola Health and Ageing Project (AHAP), were analyzed for IL-10, lipid profile, vitamin D, selenium (Se), antioxidant capacity, and MetS. RESULTS: Compared to patients, the healthy subjects exhibited higher levels of circulatory IL-10 among individuals with detectable serum IL-10 (P = 0.036). However, this difference was not observed when total subjects from both groups were compared, since more than 90% of those people were IL-10-negative. Se, vitamin D, and antioxidant levels were similar in both groups. There was a negative association between IL-10 and body mass index (BMI) (P < 0.050) and an equivocal association with vitamin D levels, whereas the association between IL-10 and other indicated variables was not significant. Significant association was observed between MetS and CVD prevalence (P < 0.001). There was a positive correlation between Se and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (P < 0.010) in healthy subjects and with TC in patients (P < 0.050). CONCLUSION: A major proportion of elderly people were serum IL-10-negative, whereas independently to IL-10, MetS was most common in patients with CVD. Weight loss may have the potential to increase IL-10 levels in the elderly. [ABSTRACT FROM AUTHOR]

Objective: Arbutin has been shown to have antioxidant and freeradical scavenging properties. The aim of this study was to investigate the effects of arbutin administration on behavioral impairment, and oxidative and nitrosative stress in a 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of Parkinson's disease (PD). Materials and Methods: PD model was developed by 4 intraperitoneal (i.p.) injections of MPTP (20 mg/kg) with 2 h intervals in mice. Experimental groups received once daily injection of saline as vehicle (control group) or arbutin (50 mg/kg, i.p.) one week before MPTP injections and this protocol was continued seven days post lesion. Behavioral deficits were evaluated using locomotion test, hanging wire test and forepaw stride length. Parameters indicating the oxidation levels including lipid peroxidation marker (TBARS), nitrite, protein carbonyl levels and antioxidant activity including ferric reducing antioxidant power (FRAP) were assessed in serum and midbrain samples. Results: Treatment with arbutin improved motor functions in an MPTP-induced PD model compared to control group (p<0.001). Mice treated with MPTP showed reduced levels of FRAP (p<0.001) and increased levels of TBARS (p<0.001), nitrite (p<0.001) and protein carbonyl (p<0.01), compared to the control group. In contrast to the MPTP group, arbutin treatment decreased the levels of TBARS (p<0.05), nitrite (p<0.05), protein carbonyl (p<0.05), and increased FRAP levels (p<0.05) in mice with PD. Conclusion: These findings suggest that arbutin attenuates the behavioral impairment and oxidative stress in a PD animal model. [ABSTRACT FROM AUTHOR]

Trace element determination is requested rarely for critically ill patients in Iran, due to the underestimation of the trace element determination by Iranian physicians. The aim was to compare the levels of Zn and Mg in a group of hemodialysis patients and normal individuals. This study shows that trace element determination is helpful for management of hemodialysis patients. Fifty-three hemodialysis patients and 51 control individuals were randomly analyzed for Zn and Mg serum levels. Comparison of before or after dialysis and with normal individuals was done and receiver operating characteristics (ROC) curves were plotted to evaluate the analytical sensitivity and specificity of Zn and Mg determination. Confidence interval for all statistical methods was 95 %. Zinc serum levels were decreased after hemodialysis insignificantly ( P = 0.201) but Mg levels were decreased significantly ( P = 0.000). Both Zn and Mg levels, before and after hemodialysis were meaningfully lower than normal controls ( P < 0.05). ROC analysis showed that the area under the curve was high for Zn levels both before and after hemodialysis but it was high for Mg only before hemodialysis. Current study shows that serum Zn and Mg measurements can have clinical importance. Both before and after hemodialysis, serum Zn = 297.5 µg/L and Mg = 2.295 µg/L are proposed as cut-off values with about 90 % specificity, for monitoring of these two element in hemodialysis patients. It is suggested that clinicians consider the measurement of these trace elements for hemodialysis patients routinely or periodically as clinical chemistry tests. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. GDM causes substantial morbidity and mortality and long- term complications. GDM-related risk factors have not been completely identified yet. Some studies have found relationship between increased serum ferritin and impaired oral glucose tolerance test but the relationship between serum ferritin and risk of GDM has been controversial. The aim of the study was to determine serum iron and ferritin levels and total iron binding capacity (TIBC) in women with GDM and comparison with normal pregnant women. Materials and Methods: This case-control study was performed among 200 pregnant women (case = 100, control = 100) who were referred to Yahya-Nejad Hospital in the second trimester in Babol from 2008 to 2009. GDM was diagnosed by impaired OGTT based on Carpenter and Coustan criteria. The 2 groups were matched in age, gestational age and parity. Results: High serum ferritin level increased the risk of gestational diabetes to 2.4-fold [OR = 2.4 (0.83-6.9) CI = 95% (P = 0.10)], while in those with low ferritin levels, the risk of developing gestational diabetes was reduced to 82% [OR = 0.8 with (0.08-0.37) CI = 95% (P = 0.001)]. Using the logistic regression model, after adjustment for BMI, the OR was 2.37 [(0.80-7.01) CI = 95% (P = 0.11)] for low ferritin level and OR = 0.20 [(0.09-0.44) CI = 95% (P = 0.0001)] for high ferritin level, which was statistically significant. Conclusion: The serum ferritin level was markedly higher in women with gestational diabetes than in normal pregnant women; therefore, high ferritin can be regarded as a significant risk factor for the development of gestational diabetes. [ABSTRACT FROM AUTHOR]

Objective: Active and passive smoking lead to the production of a number of oxidants and antioxidants with various adverse health effects compromising the immune system. Tobacco use increases the production of free radicals as well. The purpose of this study was to determine the effects of passive smoking on total antioxidant capacity (TAC) of serum and saliva in rats. Methods: This experimental study was conducted on 18 rats with an age range of 7-11 weeks weighing 160-200 g; 9 of them were exposed to cigarette smoke 3 times daily for 8 minutes. The 9 controls were not exposed to cigarette smoke. After injection of 0.2 mg/kg midazolam and 0.5 mg/kg pilocarpine, serum and saliva samples were taken from subjects in the exposure and control groups at 0, 15 and 30 days. Serum cotinine was measured using ELISA kit. TAC of saliva and serum was measured using ferric reducing antioxidant power (FRAP) assay. TAC values at different time points were statistically analyzed in each group using Repeated Measures ANOVA and compared between the two groups using t-test. Results: At baseline, no significant difference existed between the two groups in terms of serum cotinine concentration but at days 15 and 30, cotinine serum concentration significantly increased in the exposure group. At baseline and 30 days, no significant difference existed between the two groups of passive smoker and non-smoker in terms of serum TAC values but at day 15, serum TAC values were significantly higher in the exposure group. Also, TAC of salivawas significantly higher in the passive smoker group at baseline and at day 15 but at day 30, the difference in this respect between the two groups was not statistically significant. Conclusion: Based on the obtained results, changes in TAC of serum and saliva in rats due to exposure to cigarette smoke were compensated by their immune system activity. However, further investigations are still required in this respect. [ABSTRACT FROM AUTHOR]

Background: Interactions of free radicals from ionizing radiation with DNA can induce DNA damage and lead to mutagenesis and carsinogenesis. With respect to radiation damage to human, it is important to protect humans from side effects induced by ionizing radiation. In the present study,the effects of arbutin were investigated by using the micronucleus test for anti-clastogenic activity, to calculate the ratio of polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte (PCE/PCE+NCE) in order to show cell proliferation activity. Methods: Arbutin (50, 100, and 200 mg/kg) was intraperitoneally (ip)administered to NMRI mice two hours before gamma radiation at 2 and 4 gray (Gy). The frequency of micronuclei in 1000 PCEs (MnPCEs) and the ratio of PCE/PCE+NCE were calculated for each sample. Data were statistically evaluated using one-way ANOVA,Tukey HSD test, and t-test. Results: The findings indicated that gamma radiation at 2 and 4 Gy extremely increased the frequencies of MnPCE (P<0.001) while reducing PCE/PCE+NCE (P<0.001) compared to the control group. All three doses of arbutin before irradiation significantly reduced the frequencies of MnPCEs and increased the ratio of PCE/PCE+NCE in mice bone marrow compared to the non-drug-treated irradiated control (P<0.001). All three doses of arbutin had no toxicity effect on bone marrow cells. The calculated dose reduction factor (DRF) showed DRF=1.93 for 2Gy and DRF=2.22 for 4 Gy. Conclusion: Our results demonstrated that arbutin gives significant protection to rat bone against the clastogenic and cytotoxic effects of gamma irradiation. [ABSTRACT FROM AUTHOR]

One of the major challenges in gastric cancer (GC) chemotherapy is the phenomenon of multi-drug resistance (MDR). The epithelial-mesenchymal transition (EMT) and its key molecules, transforming growth factor-β (TGFβ) and SMAD2, play a central role in MDR occurrence. Tamoxifen (TAM), a triphenylethylene derivative, can overcome MDR in human gastric cancers. The aim of this study was to investigate the effect of TAM on 5-FU resistance of GC by suppressing the TGFβ1/SMAD2 signaling pathway and EMT. The MKN-45 cell line was subjected to treatment with 5-FU, TAM and a combination of both. The MTT assay was used to investigate the cytotoxic effects of 5-FU and TAM, and the DNA laddering technique was used to assess DNA fragmentation and apoptosis. Real-time RT-PCR examined the change in gene expression in EMT-related genes (SNAI2, VIM, TGFβ1 and SMAD2) . The results of the present study indicated that not only TAM treatment significantly decreased the IC50 of 5-FU (P≤0.05), but also the addition of TAM to 5-FU induced apoptosis in the MKN-45 cell line. Treatment with TAM and 5-FU significantly inhibited TGFβ1 and TGFβ1-induced expression of EMT markers (VIM and SNAI2) in MKN-45 cells (P≤0.05). The reduction of TGFβ1 targets downstream of the SMAD2 signaling pathway reversed the process of EMT and significantly increased the sensitivity of MKN-45 cells to 5-FU. The results of the present study suggested that reversal of EMT-mediated MDR via the TGFβ1/SMAD signaling pathway using TAM may be a potential new therapeutic strategy to overcome chemoresistance to 5-FU during GC chemotherapy., (© The Author(s).)

Background: Nowadays, radiotherapy is used effectively for the treatment of head and neck cancers. Mucositis is one of the most important side effects of radiotherapy. Radio-protective agents protect tissues and cells against the adverse effects due to ionizing radiation and cleave radiation-induced free radicals. Lycopene as a potent antioxidant protects cells against oxidative damage by free radical-scavenging. The present study investigated the antioxidant effect of lycopene on oral mucosa of irradiated rats., Methods: In this experimental animal study, 28 rats were placed in four groups as follows: treated with 50 mg /kg of lycopene (L50), solvent+irradiation (SR), 25 mg / kg of lycopene+irradiation (LR25), and 50 mg / kg of lycopene+irradiation (LR50). The rats received lycopene intraperitoneally. On the irradiation day (day 0) and tenth day of radiation, blood samples were taken from the animals for FRAP and TBARS tests., Results: The results showed that the LR50 group did not show mucositis higher than grade 2. There was a significant difference (p<0.05) between SR and the L50 regarding the severity of mucositis. In addition, L50 showed higher antioxidant activity and lower peroxidation than SR., Conclusion: Lycopene reduced the severity of mucositis. Therefore, it can be used as a potential and promising nutritional substance to prevent radiotherapy complications, especially in the treatment of head and neck cancers. However, further research is necessary to confirm these results., (Copyright © 2020, Babol University of Medical Sciences.)

Background: Recurrent aphthous stomatitis (RAS) is the most common inflammatory ulcerative condition of oral cavity. The aim of this study was to compare the levels of the salivary Malondialdehyde (MDA) and total antioxidant capacity (TAC) and blood parameter in RAS versus healthy controls., Methods: This case-control study consisted of 28 patients with RAS and 28 age and sex -matched control without RAS. Cell blood count was assessed by sysmex system, serum iron and total iron binding capacity was measured by standard laboratory kit and for ferritin ELISA kit was utilized. Salivary TAC and MDA level determined using FRAP and TBARS method respectively. Statistical analysis was performed using SPSS Version 21, chi-square test was used to compare proportions, and student's t-test and Mann Whitney U-test were used for the comparison of quantitative variables., Results: Salivary MDA level was significantly higher (p<0.001) and TAC level was significantly lower (p<0.042) in RAS as compared with the control group. Also, serum ferritin level was significantly higher in RAS patients (p<0.008)., Conclusion: These findings indicate the alteration of oxidant/antioxidant status was observed in recurrent aphthous stomatitis, may be also associated with changing several hematinic parameters in this study. The finding maybe helpful to clarify the etiologies of RAS and possibely to improve the management or preventive options.

Background: Cyclosporine A (CsA) is a potent immunosuppressant drug with therapeutic and toxic actions. The use of CsA is limited by its toxicity. Several researchers had proposed that oxidative stress could play an important role in CsA-induced toxicity. Arbutin has recently been shown to possess antioxidative and free radical scavenging abilities. The present study was designed to investigate the in vivo effects of arbutin on lipid peroxidation and antioxidant capacity in the serum of cyclosporine treated rats., Methods: Adult male Wistar rats were divided into six groups (n=8/group): (I) control (no CsA and arbutin administration), (II and III) were treated subcutaneously (Sc) with arbutin (50,100 mg/kg/bw), respectively, (IV) administered CsA (25 mg/kg/bw) intraperitoneally (IP), (V and VI) received the combination of CsA (25 mg/kg/bw) i.p and arbutin (50,100 mg/kg/bw) Sc daily, respectively. At the end of the treatment (after3 weeks), serum lipid peroxidation was measured by thiobarbituric acid-reacting substances (TBARS) and serum total antioxidant capacity (ferric reducing ability of plasma [FRAP]) was assayed based on spectrophotometric method., Results: TBARS had been significantly increased by CsA administration compared with control rats. Arbutin (50mg/kg/bw) completely prevented this effect, but arbutin (100 mg/kg/bw) alone or in combination with CsA significantly increased lipid peroxidation compared with controls., Conclusion: Our data indicate that arbutin (50mg/kg/bw) had protective effect in the CsA-induced toxicity but high concentration of arbutin (100mg/kg/bw) showed meaningful oxidative and lipoperoxidative effects.

Background: The mechanism of hypoglycemic and hypolipidemic activities of Pyrus biossieriana Buhse leaf extract (PbBLE) and its phytochemical component arbutin, have not been well determined. The present study was performed to understand the hypoglycemic activity mechanisms of pbBLE and arbutin more clearly., Methods: In vitro enzymatic carbohydrate digestion with PbBLE and arbutin was assessed using α-amylase and α-glucosidase powders. The enzyme solutions were premixed with PbBLE and arbutin at different concentrations (0.1, 1, 10 and 100 mg/ml). Substrate solutions and colorimetric reagents were added to the reaction. The release of glucose was determined by spectrophotometric method. Acarbose was used as the positive control., Results: The extract (10, 100 mg/ ml) completely inhibit α- amylase and α- glucosidase activities. The extract produced higher reduction of α-amylase and α-glucosidase activity than arbutin. Inhibition at various concentrations (0.1, 1, 10, 100 mg/ml) were significantly different (p<0.05)., Conclusion: Our results exhibited that both the extract and arbutin were able to suppress the enzymes strongly.

Plants with hypoglycemic properties are important in the treatment of diabetes. One of the mechanisms in reducing blood glucose is preventing the digestive absorption of glucose. The aim of this study was to evaluate the antioxidant properties of some traditional medicinal plants collected from different regions of Iran and their effects on glucose diffusion decrease. The amounts of phenolic compounds, total flavonoids, total polysaccharides, antioxidant activity and lipid peroxidation were determined respectively by folin ciocalteu, querceting, sulfuric acid, FRAP and thiobarbituric acid - reactive substanses (TBARS) in eleven confirmed traditional antihyperglycemic medicinal plants prepared at 50g/l concentrations using the boiling method. Phenolic compounds of Eucalyptus globules (100.8± 0.01 mg /g), total flavonoids content of Juglans regia (16.9± 0.01 mg /g) and total polysaccharide amount of Allium satirum (0.28± 0.05) were the highest. Significant relationship was observed between the polyphenols and flavonoids (p <0.05). The grape seed extract showed the highest antioxidant activity (133± 0.02 mg/g) together with decreased glucose diffusion as well as increased polyphenols (p <0.05), but the increase in antioxidant activity was not related to glucose diffusion. Antihyperglycemic plant extracts containing higher polyphenols showed more efficiently in vitro glucose diffusion decrease, but no significant relationship was observed between antioxidant activity increase and glucose diffusion.