Association between trace elements in cancerous and non-cancerous tissues with the risk of breast cancers in western Iran.

This study aimed to assess the tissue content of essential and toxic metals including lead (Pb), cadmium (Cd), arsenic (As), silver (Ag), aluminum (Al), chromium (Cr), copper (Cu), iron (Fe), selenium (Se), and zinc (Zn) in the breast cancerous tissues compared to the non-cancerous tissue. The biopsy specimens of 63 breast cancers along with 63 adjacent healthy tissues in Kurdistan Province, Iran, were collected from 2019 to 2020 and assayed using ICP-MS (Agilent 7900). The results of the Mann-Whitney test illustrated that the concentration of Pb, Cd, As, Cr, Cu, and Se were significantly elevated in cancerous tissue (p < 0.05), while Zn was the only trace element with higher levels in healthy subjects (p < 0.05). Moreover, weak to moderate correlations between elements were observed in the cancerous group including Al-Cr (r=0.60), As-Cu (r=0.52), and Cu-Se (r=0.56). In contrast, no correlation over 0.50 was found between trace elements in the non-cancerous group. Raw risk differences (RDs) accounted for a significant effect for Pb, Cd, As, Ag, Cr, Se, and Zn on the development of breast cancer. In conclusion, elevated levels of As, Cd, Cu, Pb, and Se may contribute to enhancing the risk of breast cancer.

Association between trace element concentrations in cancerous and non-cancerous tissues with the risk of gastrointestinal cancers in Eastern Iran.

This study was conducted to investigate the association between trace elements including cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), nickel (Ni), selenium (Se), zinc (Zn), and arsenic (As) in gastrointestinal cancer tissue and non-cancerous tissue (suspected gastrointestinal cancer) in Eastern Iran. The samples of 63 gastrointestinal cancers (stomach (n = 20), esophageal (n = 19), and colorectal (n = 24) along with 63 controls in South Khorasan Province, Iran, were collected and analyzed using ICP-MS (Agilent 7900). Our results indicated that the concentrations of Co (1.3 ± 0.8, 1.3 ± 0.8 µg kg-1), Cr (8.1 ± 7.3, 11.0 ± 14.8 µg kg-1), Ni (29.0 ± 20.1, 39.5 ± 30.2 µg kg-1), Pb (6.9 ± 4.0, 6.1 ± 4.6 µg kg-1), and Zn (867.6 ± 159.1, 935.6 ± 196.2 µg kg-1) were significantly higher among esophagus and colon cancer cases than controls (p < 0.05). Similarly, stomach cancer cases showed higher Co, Cr, Ni, Se, and Zn and lower Cu concentrations than their controls (p < 0.05). Moreover, the Spearman correlation between metals revealed a mostly low to moderate correlation between metals. Our finding illustrated that the significant risk differences of Cr, Ni, Pb, Se, and Zn metals on esophagus cancer when considered the single predictor unadjusted for other metals and covariates RD (95% CI) - Cr: -0.274 (-0.463, -0.086), Ni: -0.288 (-0.457, -0.118), Pb: -0.171 (-0.463, -0.086), Se: -0.243 (-0.434, -0.051), and Zn: -0.094 (-0.143, -0.045) respectively. This study suggests that the trace element's exposure may be associated with gastrointestinal cancer risk. Additional studies are needed to elucidate the mechanisms underlying trace element carcinogenesis further.

Relationship between gestational diabetes and serum trace element levels in pregnant women from Eastern Iran: a multivariate approach.

The prevalence of gestational diabetes mellitus (GDM) has increased over the recent decades. Exposure to environmental contaminants may be a risk factor for the development of GDM, but this is heavily dependent on particular circumstances. Studies on various areas linking various factors are therefore needed. We examined the associations between serum trace element levels and incidents of GDM among 102 pregnant women (diabetic n = 60 and healthy n = 42) living in Birjand (Iran). Blood serum samples were analyzed for concentrations of elements linked to particulate matter air pollution such as As, Cd, Cu, Hg, Mn, Ni, V, and Zn. Concentrations of As (8.58 vs. 3.15 µg/L), Cd (6.74 vs. 0.52 µg/L), and Hg (2.60 vs. 0.90 µg/L) were significantly higher in women with GDM. Risk difference (RD) estimation showed that As, 0.516 (0.355, 0.677); Cd, 0.719 (0.534, 0.904); and Hg, 0.505 (0.276, 0.735) increase GDM probability, while V lower that risk, -0.139 (-0.237, -0.042). With the principal component analysis, we were able to separate subjects according to their GDM status based on element levels. Such classification revealed very high efficiency with a true positive rate of 93%, according to linear discriminant analysis. GDM subjects presented higher levels of As, Cd, and Hg, indicating that these elements may disturb insulin metabolism and promote the development of GDM. Therefore, we conclude that systematic monitoring of trace elements followed by multivariate modeling in women planning pregnancy should be carried out to prevent the development of GDM.

Effects of Securigera Securidaca seed extract in combination with glibenclamide on antioxidant capacity, fibroblast growth factor 21 and insulin resistance in hyperglycemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Undesired effects of synthetic antidiabetic agents have made researchers to seek for safer and healthier resources. With this aspect, herbal materials have attracted substantial research interest and are being extensively investigated. Considering that herb-drug interactions can be a double-edged sword presenting both risks and benefits, investigation of such interactions is greatly in demand. AIM OF THE STUDY: to investigate possible beneficial effects of hydroalcoholic extract of SecurigeraSecuridaca seed (HESS) on antioxidant capacity, fibroblast growth factor 21 (FGF21) and insulin resistance in Streptozotocin (STZ)-induced diabetic rats, alone and in combination with glibenclamide. MATERIALS AND METHODS: Forty male Wistar rats were randomly divided in to eight equal groups including healthy and diabetic controls and six treated groups with a various doses of HESS alone and in combination with glibenclamide, for 35 consecutive days. Serum samples were taken and analyzed for biochemical profile, HOMA indexes, FGF21, oxidative/nitrosative stress and inflammatory biomarkers as compared with the controls. Moreover, total phenolic and flavonoid contents of herbal extract were assessed. RESULTS: The herbal extract was found to be rich in flavonoid and phenolic components. Both of glibenclamide and the HESS decreased glucose and insulin resistance, as well as increased body weight and insulin sensitivity. Moreover, the extract could mitigate oxidative/nitrosative stress and inflammation dose-dependently, however, the standard drug was less effective than HESS. Induction of diabetes increased FGF21 levels and both of the treatments could reduce its contents, however, glibenclamide was more effective than HESS. CONCLUSIONS: The results clearly show that there is no contradiction between HESS and glibenclamide. Moreover, the herbal extract could augment antioxidant and anti-inflammatory properties of the standard drug.

The relationship between B7 homologous 1 with interleukin-4, interleukin-17 and interferon gamma in patients with allergic rhinitis.

Background: The etiology of allergic rhinitis includes an increase in cytokine levels, including IL- 4, IL-13, IL-17, and reduction in B7 homologous 1 (B7-H1) or programmed cell death-1 ligand-1 (PD-L1), a new member of the CD28: B7 stimulant molecule family. The aim of this study was to determine the relationship between cytokines and PD-L1. Methods: In this experimental study, 80 patients with allergic rhinitis were enrolled according to inclusion and exclusion criteria. The severity and stage of the disease were determined by a specialist physician. A 5 cc venous blood sample was collected from the patients. IL-4, IL-17, INFγ and PD-L1 were measured using ELISA technique. Results: There was a significant correlation between SPD-L1 and INFγ, IL-4 and IL-17 in allergic rhinitis patients (P < 0.05). Statistical analysis based on the severity of the disease (Mild, Moderate and Severe) showed a significant positive correlation between the SPD-L1 and INFγ in all three levels (P < 0.001). There was also a significant negative correlation between SPD-L1 and two cytokines IL-4 and IL-17 (P < 0.001). Conclusion: PD-L1 may have a protective role against allergic rhinitis, although the precise mechanism requires further detailed studies.

Using Oaxaca Decomposition to Study Socioeconomic Inequity of Physical Activity among Children Aged 10-12 Years: A Study in West of Iran.

BACKGROUND: Low physical activity (PA) is increasing public health problem. The present study aimed to determine socioeconomic inequality in PA among children aged 10-12 years old in Kurdistan, west of Iran in 2015. METHODS: The present cross-sectional study was conducted on 2506 children aged 10-12 in Sanandaj, Iran, in 2015. Data on the children's level of PA were collected using the Modifiable Activity Questionnaire. The concentration index was used to measure inequality and the Oaxaca decomposition to examine the different determinants of the inequality. The data were analyzed in Stata 13 and SPSS 20. RESULTS: Of the 2506 participants, 40.90% (38.97-42.82) had insufficient PA. Girls had a lower level of PA than boys (odds ratio [OR] = 0.34; 95% confidence intervals [CI]: 0.28-0.41) and it is directly related to maternal education (OR = 1.71; 95% CI: 1.18-2.47), the family's Socioeconomic status (SES) (OR = 2.18; 95% CI: 1.56-3.05), and the place of residence (OR = 1.68; 95% CI: 1.16-2.44). The concentration index for insufficient PA was -0.25 (95 CI: -0.30 to -0.21), revealing an insufficient PA in the group with a low SES. The prevalence of insufficient PA is 51.38% (95% CI: 48.45-54.31) in poor group and 28.40% (95% CI: 22.80-33.99) in the wealthier group. The Oaxaca decomposition showed maternal education and the place of residence was the most important determinants of inequality. CONCLUSIONS: According to the findings, most of the children especially in the poor groups didn't have sufficient PA and socioeconomic factors could have the important role.

Socioeconomic Inequality in Childhood Obesity.

BACKGROUND: The aim of this study was to assess the socioeconomic inequalities in obesity and overweight in children aged 10 to 12 yr old. STUDY DESIGN: A cross-sectional study. METHODS: This study was conducted on 2506 children aged 10 to 12 yr old in the city of Sanandaj, western Iran in 2015. Body mass index (BMI) was calculated. Considering household situation and assets, socioeconomic status (SES) of the subjects was determined using Principal Component Analysis (PCA). Concentration Index was used to measure inequality and Oaxaca decomposition was used to determine the share of different determinants of inequality. RESULTS: The prevalence of overweight was 24.1% (95% CI: 22.4, 25.7). 11.5% (95% CI: 10.0, 12.0) were obese. The concentration index for overweight and obesity, respectively, was 0.10 (95% CI: 0.05, 0.15), and 0.07 (95% CI:0.00, 0.14) which indicated inequality and a higher prevalence of obesity and overweight in higher SES. The results of Oaxaca decomposition suggested that socioeconomic factors accounted for 75.8% of existing inequalities. Residential area and mother education were the most important causes of inequality. CONCLUSIONS: To reduce inequalities in childhood obesity, mother education must be promoted and special attention must be paid to residential areas and children gender.

Concurrent effects of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer, clinical output, and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia.

There are a paucity and contradicted data about the impact of concurrent heredity of polymorphic genes and risk of chronic myeloid leukemia (CML). In the present study, the concurrent effects of three polymorphisms affecting the integrity of DNA consist of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp on development of chronic myeloid leukemia were studied. Furthermore, the role of these polymorphisms in clinical and laboratory outcomes of patients was evaluated. In this case-control study, 70 CML patients and 140 healthy individuals were enrolled in the study. The clinical features of patients such as phase of disease and response to treatment and laboratory data before and after treatment with imatinib mesylate were collected. ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp single nucleotide polymorphisms were evaluated by restriction fragment length polymorphism-polymerase chain reaction. The T allele of ABCB1 C3435T, T allele of XRCC1 Arg194Trp, and C allele of ABCG2 C421A polymorphisms were significantly higher in patients than controls. TT genotype of ABCB1 and TT genotype of XRCC1 were associated with higher risk of chronic myeloid leukemia development. CC421 ABCG2/TT3435 ABCB1 and CC421 ABCG2/TT27157 XRCC1 were also correlated with a higher risk of CML. Patients with C allele of ABCB1 had poor cytogenetic response, and correlation of CC421 ABCG2/TT3435 ABCB1 diplotype with accelerated phase of CML was significant. Patients with CC421 ABCG2/TT3435 ABCB1 and CC421 ABCG2/TT27157 XRCC1 diplotypes might be at higher risk to rapid and severe development of CML and have weaker response to treatments with imatinib.

Association of HaeIII single nucleotide polymorphisms in the SLC2A1 gene with risk of diabetic nephropathy; evidence from Kurdish patients with type 2 diabetes mellitus.

AIMS: Given the growing rate of patients with type 2 diabetes mellitus, uncovering the effects of gene polymorphism on diabetes pathogenesis has attracted a lot of attention. Because glucose transporter 1 is involved in glucose uptake, the polymorphism of this gene may be an important risk factor in type 2 diabetes mellitus or in the progression of diabetes complications such as diabetic nephropathy. As far as the authors are concerned, this study is the first one aiming at evaluating the probable effects of solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) HaeIII polymorphism on clinical and laboratory outcomes of Kurdish patients with type 2 diabetes mellitus. METHODS: This study was conducted involving 126 diabetic nephropathy patients and 150 diabetic patients without renal involvement. Serum levels of Cystatin C, fasting blood glucose, creatinine and urinary albumin; levels of glycated hemoglobin and estimated glomerular filtration rate were measured. Moreover, the Hae III polymorphism of SLC2A1 gene was determined by PCR-restriction fragment length polymorphism (RFLP). RESULTS: The rate of CC genotype was higher (37%) in patients with diabetic nephropathy compared with controls. There were a significant correlation between the CC genotype and risk of diabetic nephropathy. There were significant correlations between genotypes, serum Cystatin C and estimated glomerular filtration rate in patients with diabetic nephropathy. CONCLUSIONS: The results demonstrated the high frequency of C allele of SLC2A1 HaeIII in Kurdish patients with diabetic nephropathy. It was also found that this polymorphism is a significant risk factor for diabetic nephropathy. The effect of this polymorphism on clinical and laboratory characteristics of diabetic nephropathy patients was significant.

Evaluation of screen time activities and their relationship with physical activity, overweight and socioeconomic status in children 10-12 years of age in Sanandaj, Iran: A cross-sectional study in 2015.

Background: Screen time (ST), including watching television and playing electronic games are the leading cause of a growing obesity epidemic. This study aimed to evaluate ST and its association with physical activity, overweight and socioeconomic status (SES) in children 10 to 12 years of age in Sanandaj. Methods: This study was designed as a cross-sectional study, which was conducted in Sanandaj in 2015. ST and physical activity data were collected using the Modifiable Activity Questionnaire (MAQ). Overweight indices are defined based on BMI age- and gender-specific percentiles, as proposed by WHO criteria. Considering household assets data, SES was calculated using principal component analysis (PCA). The relationship between ST and different determinants was assessed using logistic regression analysis. Results: Based on the results obtained in our study, 47.28% (95% CI: 45.33-49.24) of the participants spent more than two hours a day on television and video watching and electronic games playing. People who spend greater time on ST activities, independent of their physical activities, are more susceptible to overweight and obesity (p=0.002). People in higher socioeconomic groups spent more time on watching TV and video and playing electronic games (p=0.001). There was a direct relationship between the residential area and ST (P=0.052). ST in male was found to be greater (p=0.033). In addition, ST was also lower in school-aged children whose mothers had a greater education (p=0.56). Conclusion: Based on the results of this study, it is recommended to increase the education level and knowledge of mothers and design interventions consistent with children gender and residential location so that to reduce ST and its associated outcomes in children.

Diagnostic value of cystatin C for diagnosis of early renal damages in type 2 diabetic mellitus patients: The first experience in Iran.

BACKGROUND: Diabetic nephropathy (DN) is one of the most important complications of diabetes mellitus. Now-a-days, cystatin C (CysC) is introduced as a new marker for diagnosis of renal damages; however, use of this marker in clinical laboratories is still controversial. The present study was aimed to evaluate the diagnostic value of serum CysC for early detection or monitoring treatment of kidney damages in the Kurdish people with type 2 diabetes mellitus. MATERIALS AND METHODS: Glomerular filtration rate (GFR) was estimated by Modification of Diet in Renal Disease formula. Serum CysC and urine microalbumin were also measured in 126 diabetic and healthy subjects. Blood glycated hemoglobin (Hb) also measured in all healthy and diabetic patients. Two independent samples t-test, Mann-Whitney U-test, one-way ANOVA, and Kruskal-Wallis test, as well as Pearson/Spearman correlation coefficient statistical tests were used as appropriate. RESULTS: Serum CysC was higher (1312.41 ng/ml) in diabetic patients with GFR <60 ml/min than other subjects (993.25 ng/ml) (patients with normal kidney function and healthy subjects). A borderline significant correlation between CysC and estimating GFR (r s = -0.16, P = 0.05) but highly significant with microalbumin (r s = 0.22, P = 0.014) was observed. Serum CysC sensitivity, negative and positive predictive values were 100 and 4%. CONCLUSION: CysC cover variation of GFR and urine microalbumin, but it cannot be used as a surrogating marker of glycated Hb. According to our results, it seems that serum CysC is a useful marker for screening of DN; but it cannot be used for monitoring of treatment in diabetic patients.

Determination of Biological Variance and Validation of a Fluorometric Assay for Measurement of α-l-Iduronidase Activity in Dried Blood Spots Samples: The First Experience in Iran.

Methods for assaying lysosomal diseases in dried blood samples are very useful today due to its several advantages related to the stability of samples, its transportation, handled and analysis, and its potential use for newborn screening compared to traditional methods in leucocytes samples. For this reason, it is important to validate these assays before being used in routine laboratory. Because of different in biological markers based on ethnicity, we aimed this study to validation a DBS-based fluorometric assay for measurement of α-l-Iduronidase activity for diagnosis of MPS I patients in Iran. DBS samples were collected from 15 MPS I patients and 60 healthy age matched subjects. Diagnostic value, biological variance and α-l-Iduronidase activity were determined. DBS α-l-Iduronidase activity was significantly higher in male subjects than in female group. Using a cut-off level of 1.08 µmol/spot 20 h, sensitivity and specificity were 100 and 98 %. The linearity of test was proved and we showed that within-run and between run precision were 5.6 and 14.66 %. Measurement of α-l-Iduronidase activity in DBS samples is an accurate test for diagnosis of MPS I and because of its rapid shipping and simplicity to keeping, DBS-based enzyme activity could be considered as a useful diagnostic tool in this disease.

Determination of the best prognostic value of serum tumor markers in patients with suspected lung cancer in an Iranian population.

BACKGROUND: Finding a suitable marker with high sensitivity and specificity for early diagnosis of cancer is very desirable. This study was aimed to determine the diagnostic value of serum CYFRA21-1, carcinoembryonic antigen (CEA), and neuron-specific enolase (NSE) for screening of lung cancer patients in western Iran. METHODS: This descriptive analytical case-control study was performed on 30 subjects with malignant and 81 with benign lung cancer. Serum levels of CYFRA21-1, CEA, and NSE were determined. RESULTS: The concentration of serum tumor markers was significantly higher in the malignant group than in the benign subjects. The highest sensitivity was obtained by measurement of serum NSE (73%). The highest specificity was obtained by measurement of serum CYFRA21-1 (95%). CONCLUSIONS: Our results demonstrate the usefulness of measuring CYFRA21-1 and NSE together for early screening of lung cancer in western Iran.

Validation of Urinary Glycosaminoglycans in Iranian patients with Mucopolysaccharidase type I: The effect of urine sedimentation characteristics.

OBJECTIVE: The first line-screening test for mucopolysaccharidosis is based on measurement of urinary glycosaminoglycans. The most reliable test for measurement of urine glycosaminoglycans is the 1,9-dimethyleneblue colorimetric assay. Biological markers are affected by ethnical factors, for this reason, the World Health Organization recommends that the diagnostic test characteristics should be used to determine results for different populations. This study determines the diagnostic value of 1,9-dimethyleneblue tests for diagnosis of mucopolysaccharidosis type I patients in Iran. MATERIALS & METHODS: In addition to routine urine analysis, the qualitative and quantitative measurements of urine glucosaminoglycans were performed with the Berry spot test and 1,9-dimethyleneblue assay. Diagnostic values of the tests were determined using the ROC curve. RESULTS: Urine total glycosaminoglycans were significantly higher in male subjects than in female subjects. Glycosaminoglycan concentration was markedly decreased in specimens with elevated white blood cell and epithelial cells count. Using a cut-off level of 10.37 mg/g creatinine, sensitivity, and specificity were 100% and 97.22%, respectively, for a 1,9-dimethyleneblue colorimetric assay. CONCLUSION: Urine glycosaminoglycans concentration significantly differs in our studied population. In addition to determine diagnostic validity of the 1,9-dimethyleneblue test, our results demonstrate the usefulness of measuring glycosaminoglycans for early screening of mucopolysaccharidosis type I Iran.