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Evidence suggests the association between ambient airborne particulate matters and children’s IQ and psychological development in the early stages of life. However, data on the relationship between ambient air particulate matters and children’s IQ are rare in developing countries and less privileged areas. In this study, the association between PM10 and PM2.5 and the IQ of children in different areas were investigated in terms of pollution levels. In 2019, 369 children between the ages of 6 and 8 years old were randomly selected in three regions of southern Iran after screening through a questionnaire. In this study, PM10 and PM2.5 were determined using a direct reading device. IQ was surveyed according to Raymond B. Cattell scale I-A. The confounder factors including age, gender, economic conditions, maternal education, and type of delivery were adjusted. The average PM10 in areas with low, medium, and high pollution levels were measured to be 59.14±25.24 μg/m3, 89.7±37.34 μg/m3, and 121.44±43.49 μg/m3, respectively, while PM2.5 were found to be 38.97±16.87 μg/m3, 58±23.94 μg/m3, and 84.18±31.32 μg/m3, respectively. The IQ of children in the area with a high pollution was 16.628 lower than that in the area with low pollution (β= 16.628; [95% CI: 13.295 to 19.96]; P ≤ 0.0001). In addition, IQ in the area with high pollution level was found to be 7.48 lower than that in moderate pollution. ( β= 7.489; [95% CI: 4.109 to 10.870]; P ≤ 0.0001). Exposure to increased PM10 and PM2.5 is associated with decreased IQ in children.

Inflammatory biomarkers in exhaled breath condensate (EBC) are measured to estimate the effects of air pollution on humans. The present study was conducted to investigate the relationship between particulate matter and inflammatory biomarkers in blood plasma and exhaled air in young adults. The obtained results were compared in two periods; i.e., winter and summer. GRIMM Dust Monitors were used to measure PM10, PM2.5, and PM1 in indoor and outdoor air. A total of 40 healthy young adults exhaling air condensate were collected. Then, biomarkers of interleukin-6 (IL-6), Nitrosothiols (RS-NOs), and Tumor necrosis factor-soluble receptor-II (sTNFRII) were measured by 96 wells method ELISA and commercial kits (HS600B R&D Kit and ALX-850–037-KI01) in EBC while interleukin-6 (IL-6), sTNFRII and White Blood Cell (WBC) were measured in blood plasma in two periods of February 2013 (winter) and May 2013 (summer). Significant association was found between particulate matter and the white blood cell count (p

Olfactory ectomesenchymal stem cells (OE-MSCs) possess the immunosuppressive activity and regeneration capacity and hold a lot of promises for neurodegenerative disorders treatment. This study aimed to determine OE-MSCs which are able to augment and differentiate into functional neurons and regenerate the CNS and also examine whether the implantation of OE-MSCs in the pars compacta of the substantia nigra (SNpc) can improve Parkinson's symptoms in a rat model-induced with 6-hydroxydopamine. We isolated OE-MSCs from lamina propria in olfactory mucosa and characterized them using flow cytometry and immunocytochemistry. The therapeutic potential of OE-MSCs was evaluated by the transplantation of isolated cells using a rat model of acute SN injury as a Parkinson's disease. Significant behavioral improvement in Parkinsonian rats was elicited by the OE-MSCs. The results demonstrate that the expression of PAX2, PAX5, PITX3, dopamine transporter, and tyrosine hydroxylase was increased by OE-MSCs compared to the control group which is analyzed with real-time polymerase chain reaction technique and immunohistochemical staining. In the outcome, the transplantation of 1,1'-dioctadecyl-3,3,3'3'-tetramethyl indocarbocyanine perchlorate labeled OE-MSCs that were fully differentiated to dopaminergic neurons contribute to a substantial improvement in patients with Parkinson's. Together, our results provide that using OE-MSCs in neurodegenerative disorders might lead to better neural regeneration.

The relationship between air pollution and childhood cancer is inconclusive. We investigated the associations between exposure to ambient air pollution and childhood cancers in Tehran, Iran. This project included children between 1 and 15 years-of-age with a cancer diagnosis by the Center for the Control of Non Communicable Disease (n = 161) during 2007 to 2009. Controls were selected randomly within the city using a Geographic Information System (GIS) (n = 761). The cases were geocoded based on exact home addresses. Air pollution exposure of cases and random controls were estimated by a previously developed Land Use Regression (LUR) model for the 2010 calendar year. The annual mean concentrations of Particulate Matter ≤ 10 μm (PM10), nitrogen dioxide (NO2) and sulfur dioxide (SO2) in the locations of cancer cases were 101.97 μg/m3, 49.42 ppb and 38.92 ppb respectively, while in the random control group, respective mean exposures were 98.63 μg/m3, 45.98 ppb and 38.95 ppb. A logistic regression model was used to find the probability of childhood cancer per unit increase in PM10, NO2 and SO2. We observed a positive association between exposures to PM10 with childhood cancers. We did, however, observe a positive, but not statistically significant association between NO2 exposure and childhood cancer. Our study is the first to highlight an association between air pollution exposure and childhood cancer risk in Iran, however these findings require replication through future studies.

Evidence suggests the association between ambient airborne particulate matters and children's IQ and psychological development in the early stages of life. However, data on the relationship between ambient air particulate matters and children's IQ are rare in developing countries and less privileged areas. In this study, the association between PM

Introduction The resistance of temporal lobe epilepsy to classic drugs is thought to be due to disruption in the excitation/inhibition of this pathway. Two chloride transporters, NKCC1 and KCC2, are expressed differently for the excitatory state of Gamma-Amino Butyric Acid (GABA). The present study explored the effect of bumetanide as a selective NKCC1 inhibitor either alone or in combination with the phenobarbital in the pilocarpine model of epilepsy. Methods An animal model of Status Epilepticus (SE) was induced with pilocarpine in Wistar male rats followed by phenobarbital and or bumetanide or saline administration for 45 days after the induction of SE by Intraperitoneal (IP) injection. The rats were monitored, their behavior was recorded, and after 24 hours they were sacrificed to study the expression of NKCC1 and KCC2 using real time PCR. Results The data showed that the effects of a combination of bumetanide with phenobarbital on frequency rate and duration of seizure attack were more than those of the phenobarbital alone. In addition, in the bumetanide and combined treatment groups, NKCC1 expression decreased significantly, compared with untreated epileptic animals. A delayed decrement in NKCC1/KCC2 expression ratio after bumetanide application was also observed. Conclusion The combination of bumetanide with phenobarbital increases the inhibition of SE and maximizes the potential of GABA signaling pathway, and can be considered as an effective therapeutic strategy in patients with epilepsy.

Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of developmental disorders affecting primarily the anterior segment of the eye, often leading to secondary glaucoma. Patients with ARS may also present with systemic changes, including dental defects, mild craniofacial dysmorphism, and umbilical anomalies. ARS is inherited in an autosomal-dominant fashion; the underlying defect in 40% of patients is mutations in PITX2 or FOXC1. Here, an overview of the clinical spectrum of ARS is provided. As well, the known underlying genetic defects, clinical diagnostic possibilities, genetic counseling and treatments of ARS are discussed in detail.

In this research, the levels of polychlorinated biphenyls (PCBs) were investigated in the marine sediments of Asaluyeh harbor, in the Persian Gulf. The samples were taken from industrial, semi-industrial and urban regions. The mean concentration levels of total (Σ) 18 detected PCBs were 514.32, 144.67 and 31.6 pg/g dw for the industrial, semi-industrial and urban sampling stations, respectively. Based on a multivariate statistical analysis, it was found that high contamination levels of PCBs in sediments collected along the Persian Gulf were associated with releases from local industries. Total organic carbon (TOC) content was significantly and positively correlated with the concentrations of PCB congeners. World Health Organization toxic equivalents (TEQs) for PCBs ranged from 0.04 to 2.66 pg TEQ/g dry weight (dw) in the coastal sediments. The TEQ values in this study were higher than many reported worldwide in the literature for sediments. This suggests that there are high levels of contamination in the area due to industrial and other human activities.

Mutations in the forkhead box C1 gene (FOXC1) cause Axenfeld-Rieger syndrome (ARS). Here, we investigated the effect of four ARS missense variants on FOXC1 structure and function, and examined the predictive value of four in silico programs for all 31 FOXC1 missense variants identified to date. Molecular modeling of the FOXC1 forkhead domain predicts that c.402G> A (p.C135Y) alters FOXC1's structure. In contrast, c.378A> G (p.H128R) and c.481A> G (p.M161V) are not predicted to change FOXC1's structure. Functional analysis indicates that p.H128R reduced DNA binding, transactivation, nuclear localization, and has a longer protein half-life than normal. p.C135Y significantly disrupts FOXC1's DNA binding, transactivation, and nuclear localization. p.M161V reduces transactivation capacity without affecting other FOXC1 functions. C.1103C> A (p.T368N) is indistinguishable from wild-type FOXC1 in all tests, consistent with being a rare benign variant. Comparison of these four variants, plus 18 previously characterized FOXC1 missense variants, with predictions from four commonly used in silico bioinformatics programs indicated that sorting intolerant from tolerant (SIFT), polymorphism phenotyping (PolyPhen-2), and MutPred can sensitively identify as pathogenic only FOXC1 mutations with significant functional defects. This information was used to predict, as disease-causing, nine additional FOXC1 missense variations. Importantly, our results indicate SIFT, PolyPhen-2, and MutPred can reliably be used to predict missense variant pathogenicity for forkhead transcription factors.

Purpose Mutations in the bicoid-like transcription factor PITX2 gene often result in Axenfeld-Rieger syndrome (ARS), an autosomal-dominant inherited disorder. We report here the discovery and characterization of novel PITX2 deletions in a small kindred with ARS. Methods Two familial patients (father and son) from a consanguineous family were examined in the present study. Patient DNA samples were screened for PITX2 mutations by DNA sequencing and for copy number variation by SYBR Green quantitative polymerase chain reaction (PCR) analysis. Results We report a novel deletion involving the coding region of PITX2 in both patients. The minimum size of the deletion is 1 421 914 bp that spans one upstream regulatory element (CE4), PITX2 and a minimum of 13 neighbouring genes. The maximum size of the deletion is 3 789 983 bp. The proband (son) additionally possesses a novel 2-bp deletion in a non-coding exon of the remaining PITX2 allele predicted to alter correct splicing. Conclusion Our findings implicate a novel deletion of the PITX2 gene in the pathogenesis of ARS in the affected family. This ARS family presented with an atypical and extremely severe phenotype that resulted in four miscarriages and the death at 10 months of age of a sib of the proband. As the phenotypic manifestations in the proband are more severe than that of the father, we hypothesize that the deletion of the entire PITX2 allele plus a novel 2-bp deletion (observed in the proband) within the remaining PITX2 allele together contributed to the atypical ARS presentation in this family. This is the first study reporting on bi-allelic changes of PITX2 potentially contributing to a more severe ARS phenotype.

Introduction The repair of critical-sized defects (CSDs) are one of the most challenging orthopedic problems and the attempts for development of an ideal scaffold for treatment of large bone defect are ongoing. Aim The aim of this study was the effectiveness of hydroxyapatite-gelatin seeded with bone marrow stromal cells construct for healing of critical-sized bone defect in vivo. Material and Methods In this experimental study, the bone marrow stromal cells (BMSCs) were isolated by flushing method. For in vitro study, the cells were seeded on the scaffold and the cell viability as well as cytotoxicity were tested by MTT and LDH specific activity. The scaffold-cell construct was implanted into the critical-sized bone defect created in calvaria of Wistar male rats.15 rats were randomly divided into 3 groups (n=5), group 1 (control group): Injury without transplantation, group 2: implanted with hydroxyapatite-gelatin scaffold, group 3: hydroxyapatite-gelatin scaffold seeded with BMSCs. At different days post-implantation, the implanted site was collected and the bone healing was evaluated through H&E and Masson's Trichrome staining. ANOVA and paired t-test were used for data comparison and P

Akt isoforms have critical roles in the cause and regulation of cancer cells invasive, migration, and metastatic dissemination. In the present study, the association between Akt1 polymorphisms and endometrial cancer was investigated in patients with endometrial cancer and controls. Thirty premenopaused patients diagnosed with endometrial cancer and 30 premenopaused women with no clinically documented abnormalities of the endometrium undergoing hysterectomy were included in this study. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. There was no significant difference between Akt1 gene polymorphisms of patients (SNP1, SNP2 and SNP3) with endometrial cancer and controls (p > 0.05). Difference between alleles frequency of SNP1, SNP2, SNP3 of patients with endometrial cancer and controls was not significant (p > 0.05). SNPs (rs72715985), (rs2494750), and (rs74090038) of Akt1 gene are not associated with endometrial cancer in Iranian subjects.

Objective: It is suggested that C771G (His241Gln) polymorphism of MLXIPL gene might be a genetic risk factor for coronary artery disease (CAD); therefore, the aim of the present study was to investigate the association between C771G polymorphism of MLXIPL gene and the pathogenesis of CAD in Iranian patients with coronary artery stenosis and control subjects. Methods: Two hundred and five patients with coronary artery stenosis and 195 healthy control subjects were included in this study. MLXIPL genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (RFLP). Results: There was an association between the MLXIPL polymorphism and quantitative lipid traits in patient group. Distribution of the CC genotype of MLXIPL was more frequent in patients, (χ2=5.13; p

Background: Her-2 and ESR1 genes, that interact in the cell signaling pathway, are the most important molecular markers of breast cancer, which have been amplified or overexpressed in 30% and 70%, respectively. This study was performed to evaluate the gene expression levels of Her-2 and ESR1 genes in tumor cells and its adjacent normal tissue of breast cancer patients and compared them whit clinical-pathological features. Methods: In total, 80 tissue specimens from 40 patients, with an average age of 48.47 years, were examined by Real-time PCR technique, and ultimately evaluated the expression level of Her-2 and ESR1genes. The data were analyzed by REST 2009 V2.0.13 statistical software. Results: HER2 and ESR1 overexpression was identified in 19 (48%) and 12 (30%) of 40 patients respectively, which was higher and lower than that recorded in international statistics, respectively. ESR1 overexpression was associated with Stage 3A and lymph node involvement 2 (N2) (P = 0.04 and P = 0.047, respectively). No significant correlation was observed between the expression of HER2 and ESR1 and other clinical-pathological features, however, the relative differences were identified in the expression levels of genes between main group and groups that were classified according to the clinical-pathological features and age. Conclusions: Overexpression of Her-2 and ESR1 genes in the patients of our study are higher and lower than international statistics, respectively, indicating the differences in genetic, environmental and ethnic factors that involved in the developing of breast cancer.

Aim Life events are series of events that disrupt a person's psychological equilibrium and may enhance the development of a disorder such as suicide. Several studies have assessed a relationship between 5-hydroxytryptamine (serotonin) 2A receptor (5-HTR2A) gene polymorphisms with an increased risk of suicide. However, there has been no study about the association between three 5-HTR2A gene polymorphisms, A1438G (rs6311), T102C (rs6313) and C1354T (rs6314), suicide, stressful life, and loss events in a same time. Methods Relatives of 191 suicide victims were interviewed using a semi-structured questionnaire designed according to Iranian culture. Venous blood was taken from all subjects for DNA isolation. 5-HTR2A polymorphisms in a total of 191 suicide victims and 218 healthy controls were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Chi-squared and Fisher's exact tests were used to compare genotype and allele frequencies between suicide and control groups. Correction for multiple comparisons was calculated using Bonferroni correction. Results There was a significant association between the 102 C/C genotype of 5-HTR2A gene and suicide (к2 = 8.700, P = 0.012). Furthermore, we found that suicide victims with a 102 C/C genotype had a significantly higher number of stressful life and loss events (P 0.05). Conclusion Our results suggest that C102T (rs6313) polymorphism of 5-HTR2A gene may be involved in the susceptibility to suicide, higher number of stressful life and loss events, but A1438G (rs6311) and C1354T (rs6314) polymorphisms of 5-HTR2A gene were not associated with suicide, higher number of stressful life and loss events.

Bioflavonoid-containing diets have been reported to be beneficial in diabetes. In the current study, the effect of Biochanin A (BCA) on blood glucose, antioxidant enzyme activities and oxidative stress markers in diabetic rats were investigated. 30 male Wistar rats were divided into five groups. Two of them were selected as control; group1: control (receiving 0.5%DMSO), and group2: Control+BCA (receiving 10 mg/kg.bw BCA). Diabetes was induced in other rats with injection of (55 mg/kg.bw) streptozotocin; group3: diabetic control (receiving 0.5%DMSO), groups 4 and 5 were treated with 10 and 15 mg/kg.bw BCA respectively. After 6 weeks the following results were obtained. Fasting blood glucose (FBG), Triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and malondialdehyde (MDA) levels significantly increased and body weight, high density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD) and catalase (CAT) activity and total antioxidant status (TAS) significantly decreased in diabetic rats as compared to control rats. Oral administration of BCA in 10 and 15 mg/kg.bw, FBG, TG, TC, LDL-C, VLDL-C were decreased significantly in all treated rats. MDA was decreased in all treated rats but it was significant just in 15 mg/kg.bw BCA. HDL, CAT, SOD, and TAS were significantly increased in treated group with 15 mg/kg.bw. The obtained results indicated hypoglycemic and hypolipidemic effect of BCA. Also BCA reduced oxidative stress in diabetic rats.

Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the ‘ketogenic diet’. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360 mg/kg to induce status epilepticus (SE). At 45 day after induction of SE, metformin was injected intraperitoneally in dose of 250 mg/kg/day for 5 days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB). We have shown that this reduced expression pattern is mediated by the transcriptional co-repressor CtBP (C-terminal binding protein). Moreover, metformin decreased mechanistic target of rapamycin (mTOR) activation through activation of AMP-activated protein kinase (AMPK) signaling pathway. Our findings have been shown that metformin has anticonvulsant and antiepileptic properties, and suggesting that antiglycolytic compounds such as metformin may represent a new class of drugs for treating epilepsy.

The neurodegenerative disease glaucoma is one of the leading causes of blindness in the world. Glaucoma is characterized by progressive visual field loss caused by retinal ganglion cell (RGC) death. Both surgical glaucoma treatments and medications are available, however, they only halt glaucoma progression and are unable to reverse damage. Furthermore, many patients do not respond well to treatments. It is therefore important to better understand the mechanisms involved in glaucoma pathogenesis. Patients with Axenfeld-Rieger syndrome (ARS) offer important insight into glaucoma progression. ARS patients are at 50% risk of developing early onset glaucoma and respond poorly to treatments, even when surgical treatments are combined with medications. Mutations in the transcription factor FOXC1 cause ARS. Alterations in FOXC1 levels cause ocular malformations and disrupt stress response in ocular tissues, thereby contributing to glaucoma progression. In this study, using biochemical and molecular techniques, we show that FOXC1 regulates the expression of RAB3GAP1, RAB3GAP2 and SNAP25, three genes with central roles in both exocytosis and endocytosis, responsible for extracellular trafficking. FOXC1 positively regulates RAB3GAP1 and RAB3GAP2, while either increase or decrease in FOXC1 levels beyond its normal range results in decreased SNAP25. In addition, we found that FOXC1 regulation of RAB3GAP1, RAB3GAP2 and SNAP25 affects secretion of Myocilin (MYOC), a protein associated with juvenile onset glaucoma and steroid-induced glaucoma. The present work reveals that FOXC1 is an important regulator of exocytosis and establishes a new link between FOXC1 and MYOC-associated glaucoma.

This work aimed to determine whether seropositivity to Helicobacter pylori infection was an independent risk factor for hyperhomocysteinemia patients with cardiovascular disease. The H. pylori IgG, IgA and homocystein levels in 96 patients with cardiovascular disease and 64 participants free of cardiovascular disease as control subjects were determined by ELISA assay. The results showed that seropositivity to H. pylori IgG and IgA levels of coronary artery disease (CAD)patients was significantly higher than the controls and CAD patients with H. pylori IgG and IgA negative antibodies. A significant correlation was found between the seropositivity to H. pylori IgG and homocysteine levels of CAD patients in comparison with the controls and CAD patients with seronegativity to H. pylori IgG and IgA (r=0.233, P= 0.019 ). The involvement of H. pylori infection in atherosclerosis process was based on the chronic inflammation, which might facilitate the CAD-related pathologies. The effect of the presence of H. pylori infection on homocysteine levels elevation in the CAD patients (as a risk factor independent of other traditional factors) was remarkable.

Many cancer researchers use gene expression analysis for differentiation between tumor and normal cells for diagnostic, prognostic and therapeutic purposes. Most of studies compare either tumor cell lines by normal cell lines or tumor tissue of affected individuals by normal healthy control tissue. But expression of each special gene is unique in different individuals and also in different tissue of same individual. For this reason, here we compare the gene expression levels of SMAD7 and KLF10 in tumor cells and its adjacent normal tissue of breast cancer patients and compared them. For this purpose, a total of 40 tumor and matched tumor-free margin samples were obtained during surgery. The SMAD7 and KLF10 mRNA expression levels in tumor and marginal samples were examined by real-time quantitative PCR. Results are not concordant with previous studies and comparison of only SMAD7 or KLF10 is not useful for differentiating between tumor and margin cells, but ratio analysis of these two genes, SMAD7/ KLF10, can be indicative than study of one gene alone. We concluded that gene expression analysis of tumor cells with adjacent normal tissue are essential for precise identification and interpretation of cancer alterations and have important implications for the diagnostic and therapeutic management of cancer patients.

Aim: The association of serotonin 1A receptor (5-HTR1A) gene polymorphisms with suicidal behavior has been reported in several previous studies, but the results have been inconsistent, which might be due to ethnic differences. The aim of the present study was therefore to investigate the association between polymorphisms −1019C>G, 47C>T (Pro16Leu) and 815G>A (Gly272Asp) and suicidal behavior, taking into account age, gender, and the presence of stressful life and loss events in 1 year prior to suicide. Methods: A total of 191 suicide victims and 218 healthy control subjects were included in the present study. 5-HT1RA gene polymorphisms were determined on polymerase chain reaction–restriction fragment length polymorphism. Results: The distribution of −1019C>G genotypes was significantly different in suicide victims and healthy controls (P = 0.002), and the GG genotype was associated with a significantly higher number of more stressful life and loss events in the suicide victims (P = 0.017, P = 0.037, respectively). The distribution of 47C>T (Pro16Leu) and 815G>A (Gly272Asp) genotypes was not significantly different in the suicide victims and control subjects (P > 0.05). Moreover, these genotypes were not associated with stressful life and loss events (P > 0.05). Conclusion: The frequency of the −1019G allele in the 5-HTR1A gene was higher in suicide victims (with stressful life events) as compared with the control group. In contrast, neither 47C>T (Pro16Leu) nor 815G>A (Gly272Asp) polymorphisms were related with suicide and stressful life events.

PURPOSE: Elevation of homocysteine levels have been involved as a remarkable risk factor for cardiovascular disease. Decreased bioavailability of nitric oxide (NO) may result in abnormal reactions between the vessel wall and platelets and is thus involved in the initiation and progression of atherosclerosis. We aimed to assess the effect of a low dose oral contraceptive pills on homocysteine and NO levels which may influence the individual cardiovascular risk by regulation of endothelial function and development of atherosclerosis. METHODS: The study was conducted in 50 healthy women with normal menstrual cycles as control group and 50 healthy women receiving oral contraceptive pill for at least three menstrual cycles. Homocysteine concentration was assayed by an enzyme immunoassay method and a colorimetric assay was used for determination of NO levels. RESULTS: After 3 months of treatment homocysteine levels were significantly increased (P = 0.027) and there was a significant and considerable decrease (P = 0.048) in NO concentration of oral contraceptive pill (OCP) consumers. CONCLUSIONS: Our data indicates that OCPs increase the homocysteine (HCY) and reduce the NO levels. These findings warrant a possible implication of OCP in change of risk of development of coronary heart disease. (c) 2012 Wiley-Liss Inc.

Background: Apolipoprotein (apo) E polymorphism plays a significant role in the development of coronary disease, but their involvement in coronary artery stenosis (CAS) is controversial. Therefore, the purpose of this study was to investigate the effects of this polymorphism on atherosclerosis, and severity and extent of CAS in unrelated Iranian population. Methods: DNA was isolated from 390 study participants and APOE genotypes were determined utilizing the polymerase chain reaction and restriction fragment length polymorphism. Results: The APOE‐ε4 and ‐ε2 allele frequencies were significantly higher in the CAS patients than in the control group (P0.05). Conclusion: Our results suggest that APOE‐ε4 is a risk factor for stenosis but does not has any effect on the severity of this disease. J. Clin. Lab. Anal. 25:43–46, 2011. © 2011 Wiley‐Liss, Inc.

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

Mutations in PITX2 have been implicated in several genetic disorders, particularly Axenfeld-Rieger syndrome. In order to determine the most reliable bioinformatics tools to assess the likely pathogenicity of PITX2 variants, the results of bioinformatics predictions were compared to the impact of variants on PITX2 structure and function. The MutPred, Provean, and PMUT bioinformatic tools were found to have the highest performance in predicting the pathogenicity effects of all 18 characterized missense variants in PITX2, all with sensitivity and specificity >93%. Applying these three programs to assess the likely pathogenicity of 13 previously uncharacterized PITX2 missense variants predicted 12/13 variants as deleterious, except A30V which was predicted as benign variant for all programs. Molecular modeling of the PITX2 homoedomain predicts that of the 31 known PITX2 variants, L54Q, F58L, V83F, V83L, W86C, W86S, and R91P alter PITX2's structure. In contrast, the remaining 24 variants are not predicted to change PITX2's structure. The results of molecular modeling, performed on all the PITX2 missense mutations located in the homeodomain, were compared with the findings of eight protein stability programs. CUPSAT was found to be the most reliable in predicting the effect of missense mutations on PITX2 stability. Our results showed that for PITX2, and likely other members of this homeodomain transcription factor family, MutPred, Provean, PMUT, molecular modeling, and CUPSAT can reliably be used to predict PITX2 missense variants pathogenicity.

Cerebrospinal fluid (CSF) contains several molecules which are essential for neurogenesis. Human dental pulp stem cells (hDPSCs) are putatively neural crest cell-derived that can differentiate into neurons and glial cells under appropriate neurotrophic factors. The aim of this study was to induce differentiation of hDPSCs into neuroglial phenotypes using retinoic acid (RA) and CSF. The hDPSCs from an impacted third molar were isolated by mechanical and digestion and cultured. The cells have treated by 10−7 µM RA (RA group) for 8 days, 10% CSF (CSF group) for 8 days and RA with CSF for 8 days (RA/CSF group). Nestin, microtubule-associated protein 2 (MAP2), and glial fibrillary acidic protein immunostaining were used to examine the differentiated cells. Axonal outgrowth was detected using Bielschowsky's silver impregnation method and Nissl bodies were stained in differentiated cells by Cresyl violet. The morphology of differentiated cells in treated groups was significantly changed after 3–5 days. The results of immunocytochemistry showed the presence of neuroprogenitor marker nestin was seen in all groups. However, the high percentage of nestin positive cells and MAP2, as mature neural markers, were observed at the pre-induction and induction stage, respectively. Nissl bodies were detected as dark-blue particles in the cytoplasm of treated cells. Our findings showed the RA as pre-inducer and CSF as inducer for using in vitro differentiation of neuron-like cells and neuroglial cells from hDPSCs.

Background: Women in urban communities of Iran have the highest incidence rates of breast cancer (BC). The reasons behind this are not fully understood and many of the causes remain unexplained. Aims: The aim of this study was to examine the relationship between exposure of BC cases and exposure of the general population to long-term air pollutants in the Middle Eastern City of Tehran, Iran. Methods: Records of 1534 BC patients were obtained from Non Communicable Disease Center belong to Ministry of Health (with disease onset during 2008 to 2009). Thereafter, they were successfully geo-coded within Tehran megacity by Geographic Information System (GIS) Bureau of Iran’s Post Office based on their postal code. On the other hand, 3008 random cases were created within the city by a GIS. The individual long-term exposure to sulfur dioxide (SO2) and particulate matter ? 10 µm (PM10) air pollutants of all BC and random cases were estimated using land use regression models. Finally, bivariate correlations of the exposure of these groups were calculated. Results: The annual mean concentration of SO2 and PM10 in the BC cases were 62.9 parts per billion (ppb), and 97.6 µg/m3, respectively. While in our random points the mean exposures for mentioned pollutants were 54.1 ppb, and 93 µg/m3, respectively. The correlation of long-term exposure to SO2 between BC and random cases was positive and significant (r = 0.06, p = 0.019). Meanwhile, the correlation of long-term exposure to PM10 between BC and random cases was positive and significant (r = 0.05, p = 0.037).

Background: In addition to genetic factors, environmental factors, such as air pollution, may have a significant role in the etiology of childhood cancers (CCs). Aims: The aim of this study was to ...

BACKGROUND: Apolipoprotein E (ApoE) polymorphism plays a significant role in the development of several diseases, but its role in the preeclampsia disease incidence is not clear. Therefore, the purpose of this study was to investigate the susceptibility of some pregnant women to preeclampsia. METHODS: In a comparative cross-sectional study, the ApoE polymorphism genotypes were investigated in 100 patients with preeclampcia and 100 normal pregnant, using the polymerase chain reactions (PCR) analysis. Serum lipids and lipoproteins concentrations were also evaluated using the commercially available kits. RESULTS: The difference in distribution of the epsilon2/epsilon2, epsilon2/epsilon3, epsilon2/epsilon4, epsilon3/epsilon3, epsilon3/epsilon4 and epsilon4/epsilon4 genotypes between patient subjects and controls was not significantly (p = 0.266). The data obtained for Apo epsilon4, epsilon2 and epsilon3 alleles in the patient group was not different significantly from those obtained for the control group (p = 0.220). The VLDL and TG levels of the patient group were higher significantly than controls (p < 0.01, p < 0.01 respectively). The data obtained for HDL concentration (52.2 +/- 16.1 g/dL) of the patient group was not different significantly from controls (49.4 +/- 12.5 g/dL). The difference between LDL concentration of patients with preeclampsia and controls was not significant. The cholesterol concentration of control subjects was not different significantly from patient subjects. CONCLUSIONS: The observed profiles of ApoE alleles and genotypes frequencies suggest that Apo E polymorphism does not play a major role in the development of preeclampsia. Nonetheless, the abnormal lipid profiles that we found in patients with preeclampsia may have a genetic explanation and/or contribution.

There is evidence showing the association between connexin 37 (Cx37) C1019T polymorphism and acute myocardial infarction (AMI). Since there has been no study that takes the polymorphisms of Cx37 and connexin 40 (Cx40) into consideration at the same time, we investigated the association between AMI and the polymorphism gene of two gap junction proteins Cx 37 and Cx40 which are important in the electrical coupling between arterial myocytes.200 patients with acute myocardial infarction (AMI) and 185 healthy controls were included in this study. Cx37 and Cx40 genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).We identified that single nucleotide polymorphism (SNP) of Cx37 was significantly associated with AMI disease. Significant differences between cases and controls were observed for Cx37 genotype frequencies (p0.001, Chi2 = 16.528). The T allele of Cx37 had more frequency in the AMI group compared to the control group. (53.75% vs. 40%; p0.05). Subsequent analysis identified that, in contrast to the previous studies, there is a significant difference in women (p0.01) but not in men. We also found that the SNP of Cx40 was not significantly associated with AMI disease (p0.05). Our study showed that the -44A allele and -44AA genotype were not significantly different in the AMI and control groups (p0.05).It is suggested that the polymorphism in the Cx37 gene (but not Cx40 gene) potentially plays a significant role in the manifestation of AMI disease in Iranian population.

BACKGROUND Serum fatty acid content mainly reflects dietary fat intake. It is not known whether alterations of serum fatty acid compositions predict type 2 diabetes risk. METHODS We evaluated fatty acid contents in serum of the 76 normal and 98 diabetic adults taking part in a cross sectional study, using a gas chromatography method. RESULTS The contents of total saturated (SFAs) and monounsaturated fatty acids (MUFAs) of the diabetic subjects were significantly higher when compared to the controls (p = 0.006, p = 0.02 respectively). Serum linoleic and polyunsaturated fatty acid (PUFAs) contents of subjects with diabetes were significantly lower than the control group (p = 0.02). There was a negative correlation (p = 0.001, r = -0.429) between serum PUFAs contents and cholesterol/HDL-C ratio in the control group, whereas this correlation in people with diabetes was not significant (p = 0.12). The correlation between serum TG (triglyceride) and SFAs contents of the diabetic patients was significantly positive (p = 0.01, r = 0.252). A significant negative correlation (p = 0.001, r = -0.421) was found between PUFA contents and serum TG levels of people with diabetes; however, the same correlation for the control group was not significant (p = 0.56). CONCLUSIONS Diabetes incidence was significantly and positively associated with the proportions of serum palmitic, total saturated and monounsaturated fatty acid contents. Our findings with the use of this biomarker suggest that the dietary fat profile, particularly that of saturated and monounsaturated fatty acids, may contribute to the etiology of diabetes. It seems that patients with type 2 diabetes can have good control on lipid parameters with a higher intake of polyunsaturated fatty acids than saturated fatty acids.

It is not known whether alterations of adipose tissue fatty acid compositions predict type 2 diabetes. Our goal was to characterize the relationship between the adipose tissue fatty acid compositions and type 2 diabetes.We evaluated the fatty acid compositions of subcutaneous adipose tissue. These analyses were carried out on samples from 76 normal and 98 diabetic adults. Analysis was performed on a gas chromatograph.The adipose tissue palmitic acid composition of diabetic subjects (24.9% +/- 0.3) was significantly higher (p = 0.01) than in the controls (23.3% +/- 1.6). A significant negative correlation (r = -0.276, p = 0.001) was found between adipose tissue polyunsaturated fatty acids (PUFAs) and the Chol/HDL-C ratio of all the subjects studied (controls plus diabetic patients). A similar negative correlation (r = -0.429, p = 0.001) was identified only for control group, whereas no significant correlation (p0.05) was found for diabetic populations. The correlation between fatty acid compositions and serum lipid profiles (TG, HDL-C, Chol/HDL-C, LDL-C/HDL-C proportion) and fasting blood sugar (FBS) with HbAlc concentrations of people with diabetes and controls was not significant.A high amount of palmitic acid in adipose tissue may increase the risk of the type 2 diabetes and it seems that a high intake of PUFAs can lead to lowering of the Chol/HDL-C ratio.

Morteza Seifi1,*, Asghar Ghasemi1, Siamak Heidarzadeh2, Mahmood Khosravi3, Atefeh Namipashaki4, Vahid Mehri Soofiany5, Ali Alizadeh Khosroshahi6 and Nasim Danaei7 1Laboratory of Genetics, Legal Medicine Organization of Tabriz, Tabriz, 2Division of Microbiology, School of Public Health, Tehran University of Medical Sciences, Tehran, 3Hematology Department of Medicine Faculty, Guilan University of Medical Sciences, Rasht, 4Department of Biotechnology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, 5Faculty of Medicine, Shahid Behesti University of Medical Sciences, Tehran, 6Jarrah Pasha Medicine Faculty of Istanbul, Istanbul, 7Department of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz 1,2,3,4,5,7Iran 6Turkey