Bioengineering of fibroblast-conditioned polycaprolactone/gelatin electrospun scaffold for skin tissue engineering.

BACKGROUND: Synthetic tissue engineering scaffolds has poor biocompatiblity with very low angiogenic properties. Conditioning the scaffolds with functional groups, coating with biological components, especially extracellular matrix (ECM), is an excellent strategy for improving their biomechanical and biological properties. METHODS: In the current study, a composite of polycaprolactone and gelatin (PCL/Gel) was electrospun in the ratio of 70/30 and surface modified with 1% gelatin-coating (G-PCL/Gel) or plasma treatment (P-PCL/Gel). The surface modification was determined by SEM and ATR-FTIR spectroscopy, respectively. The scaffolds were cultured with fibroblast 3T3, then decellularized during freeze-thawing process to fabricate a fibroblast ECM-conditioned PCL/Gel scaffold (FC-PCL/Gel). The swelling and degaradtion as well as in vitro and in vivo biocompatibility and angiogenic properties of the scaffolds were evaluated. RESULTS: The structure of the surface-modified G-PCL/Gel and P-PCL/Gel were unique and not changed compared with the PCL/Gel scaffolds. ATR-FTIR analysis admitted the formation of oxygen-containing groups, hydroxyl and carboxyl, on the surface of the P-PCL/Gel scaffold. The SEM micrographs and DAPI staining confirmed the cell attachment and the ECM deposition on the platform and successful removal of the cells after decellularization. P-PCL/Gel showed better cell attachment, ECM secretion and deposition after decellularization compared with G-PCL/Gel. The FC-PCL/Gel was considered as an optimized scaffold for further assays in this study. The FC-PCL/Gel showed increased hydrophilic behavior and cytobiocompatibility compared with P-PCL/Gel. The ECM on the FC-PCL/Gel scaffold showed a gradual degradation during 30 days of degradation time, as a small amount of ECM remained over the FC-PCL/Gel scaffold at day 30. The FC-PCL/Gel showed significant biocompatibility and improved angiogenic property compared with P-PCL/Gel when subcutaneously implanted in a mouse animal model for 7 and 28 days. CONCLUSIONS: Our findings suggest FC-PCL/Gel as an excellent biomimetic construct with high angiogenic properties. This bioengineered construct can serve as a possible application in our future pre-clinical and clinical studies for skin regeneration.

Olfactory mucosa stem cells: An available candidate for the treatment of the Parkinson's disease.

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.

Oxidative stress-induced renal telomere shortening as a mechanism of cyclosporine-induced nephrotoxicity.

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.

Evaluation of metformin effects in the chronic phase of spontaneous seizures in pilocarpine model of temporal lobe epilepsy.

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.

Comparison of Bioinformatics Prediction, Molecular Modeling, and Functional Analyses of FOXC1 Mutations in Patients with Axenfeld-Rieger Syndrome.

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.

Characteristics, distribution and sources of polychlorinated biphenyls (PCBs) in coastal sediments from the heavily industrialized area of Asalouyeh, Iran.

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.

Polycyclic aromatic hydrocarbons (PAHs) in coastal sediments from urban and industrial areas of Asaluyeh Harbor, Iran: distribution, potential source and ecological risk assessment.

The distribution and toxicity levels of 16 EPA priority pollutant polycyclic aromatic hydrocarbons (PAHs) in the sediments of Asaluyeh shore, Iran were investigated. The total concentrations of the PAHs in surface sediments ranged from 1,054 to 17,448 ng/g dry weights with a mean concentration of 8,067 ng/g. The spatial distribution of PAHs showed that PAH levels are much higher in the industrial areas in comparison with urban areas. Based on diagnostic ratios, pyrogenic activities were dominant sources of PAHs pollution in sediments comparing petroleum sources. The toxic equivalent concentrations (TEQ Carc) of PAHs ranged from 172 to 2,235 ng TEQ/g with mean value of 997.9. Toxicity levels were evaluated using sediment quality guidelines (SQGs) and toxic equivalent factors. Samples were collected from industrial and urban stations in Asaluyeh shores. According to SQGs, ΣPAHs concentrations in sediments of urban areas were below the ERL (effects range low), but the industrial samples had ΣPAHs concentrations between ERL and ERM (effects range median). Furthermore, ΣHPAHs (heavy PAHs) and some individual PAHs in some industrial stations exceeded ERM, indicating adverse ecological risk effects frequently occur. Findings demonstrate that the surface sediment from Asaluyeh shore is highly to very highly contaminated with PAHs.

Association Between Genetic Variants of Akt1 and Endometrial Cancer.

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.

Association of the apolipoprotein E variants with susceptibility to pregnancy with preeclampsia.

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.

Mutations of the connexin 37 and 40 gap-junction genes in patients with acute myocardial infarction.

BACKGROUND: 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. METHODS: 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). RESULTS: 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 (p < 0.001, Chi2 = 16.528). The T allele of Cx37 had more frequency in the AMI group compared to the control group. (53.75% vs. 40%; p < 0.05). Subsequent analysis identified that, in contrast to the previous studies, there is a significant difference in women (p < 0.01) but not in men. We also found that the SNP of Cx40 was not significantly associated with AMI disease (p > 0.05). Our study showed that the -44A allele and -44AA genotype were not significantly different in the AMI and control groups (p > 0.05). CONCLUSIONS: 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.

Fatty acid composition of serum lipids in patients with type 2 diabetes.

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.

Distribution of fatty acids in adipose tissue of patients with type 2 diabetes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p > 0.05) 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. CONCLUSIONS: 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.

Influence of oral contraceptive pills on homocysteine and nitric oxide levels: as risk factors for cardiovascular disease.

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.

Serotonin 1A receptor genetic variations, suicide, and life events in the Iranian population.

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.

Exposure to ambient air pollution and socio-economic status on intelligence quotient among schoolchildren in a developing country.

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 (ß= 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. ( ß= 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.

Effect of apolipoprotein E genotypes on incidence and development of coronary stenosis in Iranian patients with coronary artery disease.

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 (P<0.05). The association of Apo E polymorphism with the severity of stenosis was evaluated, which is according to the result that apolipoprotein E alleles were not significantly different when compared with the severity of stenosis (χ(2) =0.84, P>0.05). 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.

Investigating the relationship between particulate matter and inflammatory biomarkers of exhaled breath condensate and blood in healthy young adults.

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 < 0.001), as well as plasma sTNFRII levels (p-value = 0.001). No significant relationship was found between particulate matter with RS-NOs (p = 0.128), EBC RSNOs (p-value = 0.128), and plasma IL-6 (p-value = 0.167). In addition, there was no significant relationship between interleukin-6 of exhaled air with interleukin-6 of plasma (p-value < 0.792 in the first period and < 0.890 in the second period). sTNFRII was not detected in EBC. Considering the direct effect between increasing some biomarkers in blood and EBC and particulate matter, it is concluded that air pollution causes this increasing.

Matrix metalloproteinase-9 and paraoxonase 1 Q/R192 gene polymorphisms and the risk of coronary artery stenosis in Iranian subjects.

PURPOSE: To investigate the association of matrix metalloproteinase-9 (MMP-9) and paraoxonase 1 (PON1) 192 polymorphisms with susceptibility to coronary artery stenosis (CAS) and the number of diseased vessels in patients with CAS. METHODS: The study population comprised 302 unrelated Iranian individuals, including 145 patients with CAS and 157 control subjects. Genotypes for MMP-9 and PON1 192 polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: In our study, distributions of the TT genotype of MMP-9 and the RR genotype of PON1 192 were significantly higher in patients compared with healthy control subjects (P<0.05). Subsequent analysis demonstrated that a significant difference existed in the male (TT+TC vs. CC and RR+QR vs. QQ, P<0.01) but not in the female. The associations of these polymorphisms with the severity of stenosis were also evaluated, which according to results distribution of MMP-9 and PON1 192 genotypes were not significantly different compared with the severity of stenosis (P>0.05). CONCLUSIONS: The observation indicates that the polymorphisms in the MMP-9 and PON1 192 genes potentially play a role in the manifestation of coronary atherosclerosis but does not have any effect on the number of diseased vessels in Iran.

Risk of coronary artery stenosis in Iranian type 2 diabetics: is there a role for matrix metalloproteinase-3 gene (-1612 5A/6A) polymorphism?

To investigate the association of matrix metalloproteinase-3 (MMP-3) polymorphism with susceptibility to coronary artery stenosis (CAS) and the number of diseased vessels in patients with type 2 diabetes mellitus (T2DM). The study population comprised 618 unrelated Iranian individual subjects, including 305 angiographically documented CAS patients with T2DM and 313 control subjects with T2DM. MMP3 genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. Significant differences between cases and controls were observed for MMP3 genotype frequencies (p<0.01). The 6A allele was high frequently seen in the disease group, compared with the control group (64.75 vs. 56.24%, 6A/6A + 5A/6A vs. 5A/5A, p<0.05). The association of this polymorphism with the severity of stenosis were also evaluated which according to results distribution of MMP3 genotypes were not significantly different as compared with the severity of stenosis (p>0.05). Frequency of the 6A allele of the human MMP3 gene is an independent risk factor for CAS in the Iranian T2DM studied.

Exposure to ambient air pollution and risk of childhood cancers: A population-based study in Tehran, Iran.

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.