Poly-L-lysine/hyaluronan nanocarriers as a novel nanosystem for gene delivery.

The present research comes up with a novel DNA-loaded poly-L-lysine (PLL)/hyaluronan (HA) nanocarrier (DNA-loaded PLL/HA NCs) for gene delivery applications, as a promising candidate for gene delivery into diverse cells. A straightforward approach was employed to prepare such a nanosystem through masking DNA-loaded PLL molecules by HA. Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), field emission-scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) were used to analyse the interaction of the molecules as well as the physicochemical properties of the NCs. The NCs showed a negative charge of -24 ± 3 mV, with an average size of 138 ± 6 nm, in an ellipsoid-shape with smooth surfaces. The DNA loading efficiency (LE) measured by DNA absorbance was around 95 %. The MTT assay showed that the developed NCs are non-toxic to the cells. Furthermore, the uptake of the DNA-loaded PLL/HA NCs by the human embryonic kidney (HEK)-293T cells was evaluated by a flow cytometry method, and demonstrated high potential cellular uptake over 90% for transferring the gene to HEK-293T cells at the optimised conditions. Therefore, the DNA-loaded PLL/HA NCs are the potent strategy for developing nanosystems for gene delivery applications.

A dietary pattern rich in fruits and dairy products is inversely associated to gestational diabetes: a case-control study in Iran.

BACKGROUND: Gestational diabetes mellitus (GDM) causes many problems for mother and her neonate. A healthy diet plays an important role in preventing GDM. This study aimed to investigate the relationship between major dietary patterns and the GDM. METHODS: 386 healthy and 306 GDM pregnant women (total 693) completed this case-control study. Basic information and anthropometric indices were recorded, and a food frequency questionnaire was completed. For extracting major dietary patterns, the principal component analysis was performed. Multivariable logistic regression models were used to examine whether specific dietary patterns are associated to the GDM. RESULTS: Four dietary patterns were identified: "fruits and dairy products", "red meat and plant-based foods", "snacks and high-fat foods" and "carbohydrate-rich foods". Among these major extracted dietary patterns, "fruits and dairy products" showed an inverse association to the GDM (odds ratio adjusted for confounders: 0.50, confidence interval: 0.284-0.882, p-trend = 0.019, for highest vs. lowest quartile). CONCLUSIONS: It seems using a healthy dietary pattern such as "fruits and dairy products" may decrease GDM risk.

Epigallocatechin-3-gallate enhances differentiation of acute promyelocytic leukemia cells via inhibition of PML-RARα and HDAC1.

The use of all-trans retinoic acid (ATRA) has dramatically improved the treatment and survival rate of patients with acute promyelocytic leukemia (APL). However, toxicity and resistance to this drug are major problems in the treatment of APL with ATRA. Earlier studies have suggested that the green tea polyphenol epigallocatechin gallate (EGCG) induces cell death in hematopoietic neoplasms without adversely affecting normal cells. In the present study, the potential therapeutic effect of EGCG in APL and the underlying molecular mechanisms were investigated. EGCG (100 µM) significantly inhibited proliferation and induced apoptosis in HL-60 and NB4 cells. This effect was associated with decreased expressions of multidrug resistance proteins ABCB1, and ABCC1, whereas the expressions of pro-apoptotic genes CASP3, CASP8, p21, and Bax/Bcl-2 ratio were significantly increased. EGCG, at 25 µM concentration, induced differentiation of leukemic cells towards granulocytic pattern in a similar manner to that observed for ATRA (1 µM). Furthermore, EGCG suppressed the expression of clinical marker PML/RARα in NB4 cells and reduced the expression of HDAC1 in leukemic cells. In conclusion, the results suggested that EGCG can be considered as a potential treatment for APL.

Matrix Gla protein (MGP) promoter polymorphic variants and its serum level in stenosis of coronary artery.

Although the role of matrix Gla protein (MGP) is not completely known but, its expression within subendothelial macrophages and vascular smooth muscle cells is suggested to be involved in vascular calcification. In this study, we investigated the associations between the serum MGP levels and the MGP promoter high minor allele frequency (MAF) variants with the development of stenosis in coronary arteries. Moreover, we evaluated the allele changes within predicted transcription factor elements with bioinformatics tools. 182 subjects were recruited from who underwent coronary angiography. The MGP promoter rs1800801, rs1800802 and rs1800799 genotypes and haplotypes were detected by ARMS-RFLP PCR techniques. The serum MGP concentration was measured using ELISA method. Jaspar profiles were used for scoring the polymorphic variations within the transcription factor elements. The genotype and two-allelic haplotype distributions were not significant between the patient and control groups (P > 0.05). The serum MGP levels had not significant differences between the genotypes (P > 0.1) and haplotypes (P > 0.4). Based on the prediction studies, we did not observe significant differences between the polymorphic scores in the predicted elements (P > 0.05). We concluded that the genotype and haplotype distributions of the MGP promoter high-MAF polymorphisms, as confirmed in the prediction studies and the serum MGP level are not significantly associated with the coronary artery disease. Based on the study results, the MGP protein did not play an important role in the development of stenosis of coronary arteries.

Association of OX40L gene polymorphism with multiple sclerosis in Iranians.

Introduction: The exact etiology of multiple sclerosis is unknown but recent studies indicated a link between tumor necrosis factor superfamily member 4 and the disease. Polymorphisms located in the regulatory region of the gene may affect its phenotype. Hence, we aimed to investigate the association of promoter polymorphisms of the gene with multiple sclerosis and also to estimate the frequency of haplotypes in the patients and healthy subjects. Methods: Two hundred age- and sex-matched subjects including 100 patients and 100 healthy subjects were investigated in the study. Genotype and allele distributions of rs3850641, rs1234313, and rs10912580 polymorphisms in the promoter region of the gene were investigated by polymerase chain reaction-restriction fragment length polymorphism. In addition, haplotype frequencies estimation and linkage disequilibrium analysis were performed by SNPStats web tool. Results: The distribution of AA, AG and GG genotypes of rs3850641 was significantly different between the patient and healthy groups (P = 0.009). In addition, frequencies of A and G alleles of rs3850641 were different between the groups (P < 0.001). Also the distribution of rs3850641 genotypes was different between the women of the both groups (P = 0.007). Our analysis revealed that rs3850641 AG (Odds ratio = 0.393, 95 % confidence interval = 0.170-0.907, P = 0.029) and GG (Odds ratio = 0.373, 95 % confidence interval = 0.168-0.830, P = 0.016) genotypes were associated with decreased risk of the disease. However, rs1234313 genotype and allele distributions were not different between the groups. The distribution of rs10912580polymorphism. AA, AG, and GG genotypes was significantly different between the groups (P = 0.007). rs10912580 AG genotype was associated with low risk of the disease (Odds ratio = 0.252, 95 % confidence interval = 0.102-0.623, P = 0.003). The distribution of haplotypes was statistically different between the patient and healthy groups (P < 0.001). A-G-A was the most frequent haplotype among the patients and the estimated frequency was higher than that of the control group (0.5527 versus 0.3739). Conclusion: The distribution of rs3850641 and rs10912580 genotypes was different between the patients and healthy subjects. Moreover, rs3850641 AG and GG genotypes and also rs10912580 AG genotype were associated with low risk of the disease in Iranians. Further studies with large groups are recommended to show whether genotype variation in the patients could alter the response to treatment or not.

Association between OX40L polymorphism and type 2 diabetes mellitus in Iranians.

INTRODUCTION: Diabetes mellitus (DM) is one of the leading causes of morbidity and mortality worldwide. It is a multifactorial disease that genetic and environmental factors contribute to its development. The aim of the study was to investigate the association of OX40L promoter gene polymorphisms with type 2 diabetes mellitus (T2DM) in Iranians. MATERIALS AND METHODS: Three hundred and sixty-eight subjects including 184 healthy subjects and 184 T2DM patients were enrolled in our study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to detect genotype and allele frequencies of rs3850641, rs1234313 and rs10912580. In addition, SNPStats web tool was applied to estimate haplotype frequency and linkage disequilibrium (LD). RESULTS: The distribution of tested polymorphisms was statistically different between the T2DM patients and healthy subjects (P < 0.01). rs1234313 AG (OR = 0.375, 95% CI = 0.193-0.727, P = 0.004) and rs10912580 AG (OR = 0.351, 95% CI = 0.162-0.758, P = 0.008) genotypes were associated with the decreased risk of T2DM in Iranians. Moreover, our prediction revealed that AAG (OR = 0.46, 95% CI= (0.28-0.76), P = 0.0028) and GAG (OR = 0.24, 95% CI= (0.13-0.45), P < 0.0001) haplotypes were related to the reduced risk of the disease. However, the tested polymorphisms had no effect on biochemical parameters and body mass index (BMI) in the patient group (P > 0.05). CONCLUSION: Our findings revealed that OX40L promoter gene polymorphisms are associated with T2DM. Moreover, genotype and allelic variations were related to the decreased risk of T2DM in Iranians. Further studies are recommended to show whether these polymorphic variations could affect OX40/OX40L interaction or OX40L phenotype.

Seroprevalence of visceral leishmaniasis among pregnant women in Jahrom city in Fars province, southern Iran.

Background: Visceral leishmaniasis (VL) is a public health issue in endemic countries with poor sanitation facilities. In this study, the seroprevalence rate and associated risk factors of VL were investigated during September 2020 to February 2021 in pregnant women referred to Ostad Mottahari and Peymanieh hospitals in Jahrom county, Fars province, southern Iran. Material and methods: A total of 220 serum samples of pregnant women were assessed for the presence of Anti-Leishmania infantum antibodies by direct agglutination antigen (DAT). The associated risk factors were obtained using questionnaires. Results: The overall seroprevalence of VL in pregnant women was 12.72% (28/220). Considering the antibody titer, titer 1:1600 was detected in 23 samples, titer 1:3200 in 4 samples, and titer 1:6400 in one sample. All 5 women with titer >3200 had mild fever. As such, there was a statistically significant difference regarding the age (≥39 years old with p-value: 0.01). Conclusions: We recommend an appropriate health education program for pregnant women and serological screening of VL before pregnancy in endemic cities. Moreover, we believed a need for more epidemiological studies for better understand the status of VL in pregnant women.

Association of gastric inhibitory polypeptide receptor (GIPR) gene polymorphism with type 2 diabetes mellitus in iranian patients.

INTRODUCTION: Gastric inhibitory polypeptide receptor (GIPR) encodes a G-protein coupled receptor for gastric inhibitory polypeptide (GIP), which was demonstrated to stimulate insulin secretion. Relation of GIPR gene variation to impaired insulin response has been suggested in previous studies. However, little information is available regarding GIPR polymorphisms and type 2 diabetes mellitus (T2DM). Hence, the aim of the study was to investigate single nucleotide polymorphisms (SNPs) in the promoter and coding regions of GIPR in Iranian T2DM patients. MATERIALS AND METHODS: Two hundred subjects including 100 healthy and 100 T2DM patients were recruited in the study. Genotypes and allele frequency of rs34125392, rs4380143 and rs1800437 in the promoter, 5' UTR and coding region of GIPR were investigated by RFLP-PCR and Nested-PCR. RESULTS: Our finding indicated that rs34125392 genotype distribution was statistically different between T2DM and healthy groups (P = 0.043). In addition, distribution of T/- + -/- versus TT was significantly different between the both groups (P = 0.021). Moreover, rs34125392 T/- genotype increased the risk of T2DM (OR = 2.68, 95%CI = 1.203-5.653, P = 0.015). However, allele frequency and genotype distributions of rs4380143 and rs1800437 were not statistically different between the groups (P > 0.05). Multivariate analysis showed that the tested polymorphisms had no effect on biochemical variables. CONCLUSION: We concluded that GIPR gene polymorphism is associated with T2DM. In addition; rs34125392 heterozygote genotype may increase the risk of T2DM. More studies with large sample size in other populations are recommended to show the ethnical relation of these polymorphisms to T2DM.

Lack of association between CYP27B1 gene polymorphism and type 2 diabetes mellitus in Iranian patients.

Purpose: Type 2 diabetes mellitus (T2DM) is a global health problem with multiple etiological factors. Previous studies indicated that 1- alpha, 25-dihydroxyvitamin D3, a molecule that is produced by CYP27B1, could protect insulin-secreted cells from destruction by immune cells. The aim of the study was to investigate the CYP27B1 promoter gene polymorphism in T2DM. Methods: Two hundred subjects including 100 T2DM and 100 healthy individuals were recruited in the study. ARMS-PCR technique was used to identify rs10877012 genotypes in the 5' region of CYP27B1. Results: The frequency of CC, CA, and AA genotype was 61/50, 31/39, and 8/11, respectively in T2DM patients compared to healthy subjects. There was no significant difference between both groups in regarding to genotype and allele distribution (P > 0.05). CA (RR = 1.535, 95% CI = 0.841- 2.802) and AA (1.677, 95% CI = 0.627-4.490) genotypes had no association with increased risk of T2DM. In addition, CA + AA versus CC showed no increased risk for T2DM (RR = 0.639, 95% CI = 0.365-1.121). Conclusion: We found no association between rs10877012 polymorphism and T2DM. There was no increased risk of this polymorphism in T2DM. Further studies with large groups are suggested in other populations to better understand the relation of CYP27B1 gene variation, especially its ethnicity-dependent relation with T2DM.

Gene expression pattern in severely progressing covid-19 patients is related to diabetes mellitus type 1: A functional annotation analysis.

Aims: The aim of this study was to extract the signaling mediators or biological pathways that link covid-19 to other diseases such as type 1 diabetes mellitus (T1DM). Methods: Microarray data of covid-19 (GSE164805) was extracted from Gene Expression Omnibus (GEO) and analyses were performed by R package and GEO2R. Functional enrichment analysis was done to extract enriched molecular pathways (MP), biological process (BP) and molecular function (MF). Then commonly up- and down-regulated genes in covid-19 and T1DM were extracted by comparing deferentially expressed genes (DEGs) of GSE164805 and GSE9006. Results: Down-regulated DEGs in the severely progressing covid-19 patients (SPCP) had a link to T1DM. Major histocompatibility system (MHC) class II, gamma interferon (IFNγ), and IL-1B were enriched in extracted pathway that leads to T1DM. In addition, comparing extracted DEGs from GSE164805 and GSE9006 indicated that MTUS1, EGR1 and EGR3 are the genes that are up-regulated in both SPCP and T1DM. Conclusion: The findings of this study indicate that coincidence of SARS-COV-2 infection and T1DM may increase the severity of both diseases. Although covid-19 reduced the T cell mediated immune response, but increased mediators of T-cell signaling pathway such as IL-1 in both diseases. This could potentiate the inflammation response and worsens the severity of covid-19 cytokine storm or increase the resistance to insulin.

Latent infections, coronavirus disease 2019 and psychiatric disorders: The friend of my enemy.

Recent reports revealed an increased rate of hospitalization and mortality of coronavirus disease 2019 (COVID-19) among patients with psychiatric disorders. On the other hand, there is a link between latent infections, including Toxoplasma gondii, herpes simplex virus type 1 (HSV-1) and cytomegalovirus (CMV) with psychiatric disorders. We individually assessed data regarding 1) the mortality rate of COVID-19 among individuals with psychiatric disorders; 2) the association of latent infections in COVID-19 patients and 3) the association between latent infections and psychiatric disorders. We developed the hypothesis that latent infection could increase the risk of severe COVID-19 among patients with psychiatric disorders. Cumulative evidence proposed that infection with toxoplasmosis, CMV and HSV-1 could increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-Co-V2) infections among patients with psychiatric disorders probably by induction of hyperinflammatory conditions. These infections are also associated with hyperinflammation and T cell exhaustion, which has also been observed in both schizophrenia and COVID-19. This hypothesis provides new insights into the role of latent infections in increasing the mortality rates of COVID-19 among individuals with psychiatric disorders. Strategies for screening, early diagnosis and treatment of these infections could be recommended for COVID-19 patients with a background of psychiatric disorders.

Intercalation of curcumin into liposomal chemotherapeutic agent augments apoptosis in breast cancer cells.

Resistance to common chemotherapeutic agents is a frequent phenomenon in late-stage breast cancers. An ideal system capable of the co-delivery of hydrophobic and hydrophilic chemotherapeutic agents can regulate the dosage and co-localization of pharmaceutical compounds and thereby improve the anticancer efficacy. Here, for the first time, we have intercalated curcumin (Cur) into a double-layered membrane of cisplatin (Cis) liposomes to obtain a dosage controlled co-delivery formulation, capable of inducing apoptosis in breast cancer cells. The concentrations of Cur and Cis in nanoliposome (Cur-Cis@NLP) were optimized by response surface methodology (RSM); RSM optimization showed 99.81 and 23.86% entrapment efficiency for Cur and Cis, respectively. TEM analysis demonstrated the fabrication of nanoparticles with average diameter of 100 nm. The anticancer and apoptotic effects of Cur-Cis@NLPs were also evaluated using MTT assay, fluorescent staining and flow cytometry assays. Cytotoxicity assessments of various Cur-Cis@NLPs concentrations demonstrated a concentration-dependent manner. In comparison to free and liposomal Cis, Cur-Cis@NLP reduced breast cancer cells' viability (82.5%) in a significant manner at a final concentration of 32 µg.mL-1 and 20 µg.mL-1 of Cur and Cis, respectively. Combination index values calculation of Cur-Cis@NLP showed an overall CI value <1, indicating synergetic effect of the designed co-delivery system. Additionally, flow cytometry assay demonstrated Cur-Cis@NLPs triggered apoptosis about 10-folds higher than liposomal Cis. This co-drug delivery system has a potential for the encapsulation and release of both hydrophobic and hydrophilic drugs, while taking the advantages of the reduced cytotoxic effect along with achieving high potency.

Infections, inflammation, and risk of neuropsychiatric disorders: the neglected role of "co-infection".

Neuropsychiatric disorders (NPDs) have multiple etiological factors, mainly genetic background, environmental conditions and immunological factors. The host immune responses play a pivotal role in various physiological and pathophysiological process. In NPDs, inflammatory immune responses have shown to be involved in diseases severity and treatment outcome. Inflammatory cytokines and chemokines are involved in various neurobiological pathways, such as GABAergic signaling and neurotransmitter synthesis. Infectious agents are among the major amplifier of inflammatory reactions, hence, have an indirect role in the pathogenesis of NPDs. As such, some infections directly affect the central nervous system (CNS) and alter the genes that involved in neurobiological pathways and NPDs. Interestingly, the most of infectious agents that involved in NPDs (e.g., Toxoplasma gondii, cytomegalovirus and herpes simplex virus) is latent (asymptomatic) and co-or-multiple infection of them are common. Nonetheless, the role of co-or-multiple infection in the pathogenesis of NPDs has not deeply investigated. Evidences indicate that co-or-multiple infection synergically augment the level of inflammatory reactions and have more severe outcomes than single infection. Hence, it is plausible that co-or-multiple infections can increase the risk and/or pathogenesis of NPDs. Further understanding about the role of co-or-multiple infections can offer new insights about the etiology, treatment and prevention of NPDs. Likewise, therapy based on anti-infective and anti-inflammatory agents could be a promising therapeutic option as an adjuvant for treatment of NPDs.

Association of arginine vasopressin (AVP) promoter polymorphisms with preeclampsia.

OBJECTIVES: Preeclampsia (PE) is a disease of pregnancy characterized by early onset of maternal hypertension and proteinuria. New findings indicate that arginine vasopressin (AVP) may be a contributing factor to ignite PE. The aim of this study was to identify if there is any correlation between arginine vasopressin promoter polymorphisms and PE. STUDY DESIGN: Venous blood samples of 100 PE and 100 normal pregnant women were obtained for DNA extraction to identify the polymorphisms of AVP promoter by RFLP and nested-PCR techniques. MAIN OUTCOME: rs3729965 polymorphism of PE women was detected to have significant correlation with body mass index (BMI) (P = 0.028). RESULTS: Statistical analysis of three polymorphisms namely rs3729965, rs61138008 and rs3761249 of preeclamptic women (PEW) and none preeclamptic pregnant women (NPEW) revealed that rs3729965 genotypic distribution was significantly different between both groups (P = 0.04). Further analysis revealed that rs3729965 CT genotype of PEW had significant correlation to their BMI (P = 0.028). CONCLUSION: Polymorphic variants located on the promoter region of AVP are associated with PE. Thus we hypothesize that allelic variation may have a role in increasing the risk of developing PE.

Effect of Genistein in Comparison with Trichostatin A on Reactivation of DNMTs Genes in Hepatocellular Carcinoma.

Background and Aims: DNA methylation and histone modification are epigenetic modifications essential for normal function of mammalian cells. The processes are mediated by biochemical interactions between DNA methyltransferases (DNMTs) and histone deacetylases. Promoter hypermethylation and deacetylation of tumor suppressor genes play major roles in cancer induction, through transcriptional silencing of these genes. DNA hypermethylation is carried out by a family of DNMTs including DNMT1, DNMT3a and DNMT3b. In hepatocellular carcinoma, a significant positive correlation between over-expression of these genes and cancer induction has been reported. The DNA demethylating agent genistein (GE) has been demonstrated to reduce different cancers. Previously, we reported that GE can induce apoptosis and inhibit proliferation in hepatocellular carcinoma PLC/PRF5 and HepG2 cell lines. Besides, histone deacetylase inhibitors, such as trichostatin A (TSA), were successfully used to inhibit cancer cell growth. The present study was designed to assess the effect of GE in comparison with TSA on DNMT1, DNMT3a and DNMT3b gene expression, cell growth inhibition and apoptosis induction in the HepG2 cell line. Methods: Cells were seeded and treated with various doses of GE and TSA. The MTT assay, flow cytometry assay, and real-time RT-PCR were used to determine viability, apoptosis, and DNMT1, DNMT3a and DNMT3b gene expression respectively. Results: Both agents inhibited cell growth, induced apoptosis and reactivated DNMT1, DNMT3a and DNMT3b gene expression. Furthermore, TSA demonstrated a significantly greater apoptotic effect than the other agent, whereas GE improved gene expression more significantly than TSA. Conclusions: Our findings suggest that GE and TSA can significantly inhibit cell growth, induce apoptosis and restore DNMT1, DNMT3a and DNMT3b gene reactivation.

In Vitro Effect of the Histone Deacetylase Inhibitor Valproic Acid on Viability and Apoptosis of the PLC/PRF5 Human Hepatocellular Carcinoma Cell Line

The nucleosome is the fundamental building block of eukaryotic chromatin formed by DNA and histone proteins. Chromatin modifications such as acetylation, methylation, and phosphorylation are necessary for protection, replication, and gene transcription. Histone deacetylases (HDACs) are a group of enzymes that remove acetyl groups to re-establish positive charges on histones and aberrant deacetylation may lead to tumorigenesis in different tissues. Histone deacetylase inhibitors (HDACIs) are a class of chemotherapeutic agent that can reactivate gene expression and inhibit the growth of tumor cells by histone deacetylase inhibition. HDACI valproic acid (VPA) has shown potent anticancer effects in vitro and in vivo. Previously, we reported that VAP can inhibit the growth and induce apoptosis of human colon carcinoma HT 29 and hepatocellular carcinoma HepG 2 cells. The aim of the present study was to access the effect of VPA on proliferation and apoptosis of the human hepatocellular carcinoma (HCC) PLC/PRF5 cell line. Materials and Methods: PLC/PRF5 cells were treated with VPA and then MTT and flow cytometry assays were used to determine the effects on viability and apoptosis, respectively. Results: VPA inhibited cell growth and induced apoptosis in PLC/PRF5 cells significantly. Discussion: Our results clearly demonstrated that VPA has inhibitory and apoptotic effects. Conclusion: VPA can significantly inhibit the growth of HCC cells and play a significant role in apoptosis induction.

SNP haplotyping technique for evaluation of MGP 5' UTR power in osteoblast cells.

Matrix Gla protein (MGP) is involved in calcium trafficking and arterial calcification. The aim of study was to investigate the role of three polymorphisms within the MGP gene promoter region on reporter gene (luciferase) expression level. The fragments containing rs1800799 (C/T), rs1800802 (T/C), and rs1800801 (G/A) sites were constructed and transferred into human G292 osteoblast cells using pGL3-Basic plasmid. The reporter gene expression was calculated for the high and low frequency polymorphic haplotypes (CTG and TCA, respectively). Results showed that the reporter gene expression levels are not statistically different (p > 0.3). We concluded that the investigated polymorphic sites are not able to change the gene expression pattern in human G292 osteoblast cells.

Relationships of colorectal cancer with dietary factors and public health indicators: an ecological study.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in Iranian women and fifth in men. The aims of this study were to investigate the relation of dietary factors and public health indicators to its development. MATERIALS AND METHODS: The required information (2001-2006) about risk factors was obtained from the Non- Communicable Disease Surveillance Centre (NCDSC) of Iran. Risk factor data (RFD) from 89,404 individuals (15-64 years old) were gathered by questionnaire and laboratory examinations through a cross sectional study in all provinces by systematic clustering sampling method. CRC incidence segregated by age and gender was obtained from Cancer Registry Ministry of Health (CRMH) of Iran. First, correlation coefficients were used for data analysis and then multiple regression analysis was performed to control for confounding factors. RESULTS: Colorectal cancer incidence showed a positive relationship with diabetes mellitus, hypertension, lacking or low physical activity, high education, high intake of dairy products, and non-consumption of vegetables and fruits. CONCLUSIONS: We concluded that many dietary factors and public health indicators have positive relationships with CRC and might therefore be targets of preliminary prevention. However, since this is an ecological study limited by potential ecological fallacy the results must be interpreted with caution.

Lack of association between glutathione peroxidase1 (GPx1) activity, Pro198Leu polymorphism and stenosis of coronary arteries: A population-based prediction.

BACKGROUND: We studied the association between erythrocyte glutathione peroxidase1 (GPx1) activity and rs1050450 (Pro198Leu) site with the stenosis of coronary arteries and, evaluated the Pro/Leu position within the predicted tertiary structure. METHODS: Subjects were recruited from who underwent coronary angiography (controls; n = 55, Stenosis < 5% and Patients; n = 95, Stenosis ≥ 50%). The GPx1 activity and rs1050450 C/T variants were determined using enzyme assay and RFLP-PCR techniques, respectively. The conserved regions and GPx1 tertiary structure were predicted using bioinformatics tools. RESULTS: We did not find significant association between GPx1 activity (P = 0.96), rs1050450 genotype distribution and coronary artery disease (adjusted OR = 0.79; 95%CI 0.28-2.2, P = 0.6). The polymorphic variants were not located at the predicted structural and functional domains so that it had not the significant role on the GPx1stability and function. CONCLUSIONS: In agreement with the results predicted from bioinformatics tools, we suggested that the GPx1 activity and rs1050450 (Pro198Leu) site are not involved in the development of stenosis of coronary arteries in the study population.

No association between MGP rs1800802 polymorphism and stenosis of the coronary artery.

BACKGROUND AND OBJECTIVES: Matrix Gla protein (MGP) was originally isolated from bone but it is known to be expressed in several tissues including kidney, lung, heart, cartilage and vascular smooth muscle cells (VSMC) of the blood vessel wall. Since it inhibits calcification in subendothelial space of vessels thus, we evaluated the association of rs1800802(T > C) polymorphism and stenosis of the coronary artery. DESIGN AND SETTING: Cross-sectional case-control. SUBJECTS AND METHODS: One hundred eighty two subjects recruited on the basis of study protocol from who underwent coronary angiography. The controls (n=70) had normal coronary arteries (up to 5% stenosis). The patients (n=112) subdivided into three subgroups; single-vessel disease (SVD), two-vessel disease (2VD) and three-vessel disease (3VD) based on the number of stenosed coronary vessels (at least 50% stenosis). rs1800802 (T > C) polymorphism was determined by PCR-RFLP technique. RESULTS: Genotype distribution was not significant between control and patient groups. In addition, there were no significant differences between rs1800802 (T > C) frequency and gender (P=.092), and also patient subgroups (one-, two- and three vessel disease) (P=.840). CONCLUSION: We concluded that rs1800802 (T > C) polymorphism within the MGP promoter is not related to stenosis of the coronary artery.