CpG Island Methylation of the Rap1Gap Gene in Medullary Thyroid Cancer.

BACKGROUND: Medullary thyroid cancer (MTC) is a rare type of neuroendocrine tumor. This study aimed to investigate the gene and protein expression of RAP1GAP and DNA methylation patterns of its CpG74a , CpG74b , and CpG24 in an Iranian population with MTC. METHODS: In this case-control study, we selected 55 individuals who underwent thyroidectomy in Erfan hospital, Tehran, between 2018 and 2020. Samples were divided into normal thyroid tissues (control; n=20), benign nodule (n=20), and MTC (n=15). DNA methylation patterns were investigated using MSP (methylation-specific PCR). The protein level and mRNA expression of RAP1GAP were also evaluated using western blotting and real-time PCR, respectively. RESULTS: The hyper-methylation rates of CpG24 and CpG74a in the MTC samples were considerably higher than the controls (83% versus 15% and 74% versus 17%, respectively; P<0.001). The methylation/unmethylation ratio of CpG74a , and CpG24 was considerably higher than the controls (P<0.001). The methylation/unmethylation ratio of CpG24 in the benign nodules was also considerably greater than the controls (P<0.001). The mRNA expression and the protein level of RAP1GAP in the MTC group were considerably lower than the controls (P=0.005 and P=0.035, respectively). In the MTC group, aberrant methylation of CpG74a and CpG24 was significantly correlated with decreasing expression of the Rap1Gap gene (R2 : 0.23; P=0.032 and R2 : 0.56; P=0.001, respectively). CONCLUSION: Hyper-methylation in CpG24 and CpG74a and decreasing expression of RAP1GAP can be considered as diagnostic biomarkers for MTC.

Comparing Oxidative Stress Status Among Iranian Males and Females with Malignant and Non-malignant Thyroid Nodules.

BACKGROUND: Oxidative stress is commonly accrued in thyroid tissue during hormone synthesis. OBJECTIVES: We aimed to examine oxidative stress in patients with thyroid cancer, benign thyroid nodules, and healthy individuals. METHODS: In this study, 138 individuals were involved. Among the selected participants, 108 had thyroid nodules, including 30 papillary thyroid cancer (PTC), 30 follicular thyroid cancer (FTC), six anaplastic thyroid cancer (ATC), 12 medullary thyroid cancer (MTC), and 30 benign nodules. In addition, 30 individuals were selected as a healthy control group. The levels of total antioxidant capacity (TAC) and total oxidant status (TOS) of thyroid tissue were measured using the ELISA method, and the oxidative stress index (OSI) was calculated. RESULTS: The TAC level was significantly lower in MTC and FTC subtypes than in controls. The TOS level was considerably higher in the MTC group than in the control and benign nodule groups. The TOS level was not changed in other groups. The OSI was considerably higher in MTC and FTC subtypes. The TAC and OSI in benign nodules were significantly lower and higher than those of controls, respectively. The OSI was higher in female patients than in males. CONCLUSIONS: The OSI can not be considered a diagnostic biomarker for benign nodules and MTC. The diverse oxidative stress status between genders may be related to the elevated cancer incidence in females.

A single injection of vitamin D3 improves insulin sensitivity and ß-cell function but not muscle damage or the inflammatory and cardiovascular responses to an acute bout of resistance exercise in vitamin D-deficient resistance-trained males.

Vitamin D deficiency is now a recognised problem affecting multiple physiological functions. The aim of the present study was to evaluate the effect of a single dose of vitamin D3 injection on the inflammatory, muscular damage, metabolic and cardiovascular responses to an acute bout of resistance exercise (RE) in vitamin D-deficient resistance-trained males. Blood samples from fourteen vitamin D-deficient resistance-trained males were obtained during two separate trials: lower vitamin D (LVD) and higher vitamin D (HVD, after vitamin D3 injection). Metabolic, inflammatory, muscle damage and cardiovascular markers were evaluated at baseline, immediately and 1 h after RE. There were significant trial-by-time interactions for insulin and homeostatic model assessment of insulin resistance (HOMA-IR) which significantly (P < 0·05) declined for 1 h after RE in the HVD trial compared with the LVD trial. Homeostasis model assessment of ß-cell function (HOMA-ß) declines at 1 h post-RE in the HVD trial. There was also a time effect for blood sugar which significantly (P < 0·05) decreased and for creatine kinase, lactate dehydrogenase and IL-6 which increased significantly 1 h post-RE in both trials. There were no significant changes in other inflammatory and cardiovascular markers following both trials. A single injection of vitamin D3 improved insulin resistance and ß-cell function following RE in previously vitamin D-deficient resistance-trained males. Conversely, the injection did not change muscle damage and the inflammatory response to acute RE. Intramuscular vitamin D replacement may have key implications for the promotion of glucose metabolism and lowering the risk of diabetes in vitamin D-deficient individuals.

Specific Targeting of HER2-Positive Head and Neck Squamous Cell Carcinoma Line HN5 by Idarubicin-ZHER2 Affibody Conjugate.

BACKGROUND: Expression of human epidermal growth factor receptor type 2 (HER2) in head and neck squamous cell carcinoma (HNSCC) cell line HN5 can be employed with great opportunities of success for specific targeting of anti-cancer chemotherapeutic agents. OBJECTIVE: In the current study, HER2-specific affibody molecule, ZHER2:342 (an engineered protein with great affinity for HER2 receptors) was selected for conjugation to idarubicin (an anti-neoplastic antibiotic). METHOD: ZHER2:342 affibody gene with one added cysteine code at the its 5' end was synthesized de novo and then inserted into pET302 plasmid and transferred to E. Coli BL21 hosting system. After induction of protein expression, the recombinant ZHER2 affibody molecules were purified using Ni- NTA resin and purity was analyzed through SDS-PAGE. Affinity-purified affibody molecules were conjugated to idarubicin through a heterobifunctional crosslinker, sulfosuccinimidyl 4-(Nmaleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC). Specific toxicity of idarubicin-ZHER2 affibody conjugate against two HER2-positive cells, HN5 and MCF-7 was assessed through MTT assay after an exposure time of 48 hours with different concentrations of conjugate. RESULTS: Idarubicin in the non-conjugated form showed potent toxic effects against both cell lines, while HN5 cells were significantly more sensitive compared to MCF-7 cells. Dimeric ZHER2 affibody showed a mild decreasing effect on growth of both HN5 and MCF-7 cells at optimum concentration. Idarubicin-ZHER2 affibody conjugate at an optimum concentration reduced viability of HN5 cell line more efficiently compared to MCF-7 cell line. CONCLUSION: In conclusion, idarubicin-ZHER2 affibody conjugate in optimum concentrations can be used for specific targeting and killing of HN5 cells.

Coenzyme Q10 supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders.

Antioxidants and oxidative stress can participate in pathobiochemical mechanisms of autism spectrum disorders (ASDs). The aim was to identify the effects of early CoQ10 supplementation on oxidative stress in children with ASDs. Ninety children with ASDs were included in this study, based on DSM-IV criteria and using Childhood Autism Rating Scale (CARS) scores. Concentrations of CoQ10, MDA, total antioxidant status (TAS) assay, and antioxidant enzymes (superoxide dismutase or SOD and glutathione peroxidase or GPx) activity were determined in serum before and after 100 days of supportive therapy with CoQ10 at daily doses of 30 and 60 mg. Data on children's behavior were collected from parents and babysitters. CoQ10 supportive therapy was determined after three months with daily dose 2 ͯ 30 mg improved oxidative stress in the children with ASDs. A relation was seen between serum MDA (r2 = 0.668) and TAS (r2 = 0.007), and antioxidant enzymes (SOD [r2 = 0.01] and GPx [r2 = 0.001]) activity and CARS score. Based on the results, high doses of CoQ10 can improve gastrointestinal problems (P = 0.004) and sleep disorders (P = 0.005) in children with ASDs with an increase in the CoQ10 of the serum. We concluded that the serum concentration of CoQ10 and oxidative stress could be used as relevant biomarkers in helping the improvement of ASDs.

Endothelin-1 (ET-1) stimulates carboxy terminal Smad2 phosphorylation in vascular endothelial cells by a mechanism dependent on ET receptors and de novo protein synthesis.

OBJECTIVE: G protein-coupled receptor (GPCR) agonists through their receptors can transactivate protein tyrosine kinase receptors such as epidermal growth factor receptor and serine/threonine kinase receptors most notably transforming growth factor (TGF)-ß receptor (TßRI). This signalling mechanism represents a major expansion in the cellular outcomes attributable to GPCR signalling. This study addressed the role and mechanisms involved in GPCR agonist, endothelin-1 (ET-1)-mediated transactivation of the TßRI in bovine aortic endothelial cells (BAECs). METHOD: The in-vitro model used BAECs. Signalling intermediate phospho-Smad2 in the carboxy terminal was detected and quantified by Western blotting. KEY FINDING: ET-1 treatment of BAECs resulted in a time and concentration-dependent increase in pSmad2C. Peak phosphorylation was evident with 100 nm treatment of ET-1 at 4-6 h. TßRI antagonist, SB431542 inhibited ET-1-mediated pSmad2C. In the presence of bosentan, a mixed ETA and ETB receptor antagonist ET-1-mediated pSmad2C levels were inhibited. The ET-mediated pSmad2C was blocked by the protein synthesis inhibitor, cycloheximide. CONCLUSION: In BAECs, ET-1 via the ETB receptor is involved in transactivation of the TßRI. The transactivation-dependent response is dependent upon de novo protein synthesis.

Effect of Silibinin on Maspin and ERα Gene Expression in MCF-7 Human Breast Cancer Cell Line.

BACKGROUND AND OBJECTIVE: According to reports, a serine protease inhibitor (Maspin) suppresses metastasis, invasion and angiogenesis in breast and prostate cancers. Silibinin is a natural polyphenolic flavonoid with anti-cancer activity. We assessed the effects of silibinin on cell viability, maspin and ERα gene expression in MCF-7 cell line. METHODS: The human MCF-7 breast cancer cell line was cultured in Dulbecco's Modified Eagle's Medium (DMEM) and treated with different concentrations of silibinin (100-600 µg/mL) for 24, 48 and 72 hours. The cytotoxic effect of silibinin on MCF-7 viability was determined using Methyl-Thiazolyl-Tetrazolium (MTT) assay by IC50 determination. The fold changes of Maspin and ERα expression were determined by reverse-transcription real-time Polymerase Chain Reaction (PCR). All experiments on the cells were performed in triplicates. RESULTS: The maximum inhibitory effect of silibinin on cell viability was observed at 600 µg/mL after 72-hour incubation (p = 0.001). Incubation of the cells with silibinin for 48 and 72 hours significantly decreased IC50 values to 250 and 207 µg/mL (p = 0.005 and p= 0.006), respectively. The expression of maspin and ERα in the treated cells compared to controls was significantly decreased following treatment with different concentrations of silibinin during a 24-hour period. CONCLUSIONS: Silibinin reduces both maspin and ERα gene expression in MCF-7 cell line. The therapeutic effect of silibinin on the treatment of breast cancer may be mediated by the reduction of ERα expression. For verifying this hypothesis and the possible therapeutic implication of silibinin on breast cancer, further studies in this direction are necessary.

Increased Serum Levels of Tumor Necrosis Factor-Alpha, Resistin, and Visfatin in the Children with Autism Spectrum Disorders: A Case-Control Study.

Background. Autism spectrum disorders (ASDs) are complex disorders where the pathogenesis is not fully understood. Several proinflammatory and immunoinflammatory disturbances have been observed in the etiology of ASD. There is, however, limited knowledge on variations of adipokines in ASD. The present study aimed to analyze the serum levels of resistin, visfatin, and tumor necrosis factor-alpha (TNF-α) in children with ASD in relation to body weight, gender, and ASD severity level. Method. In total, 30 children with ASD (mean age: 7.72 ± 2.65 y; range; 4-12 y) and 30 healthy children (mean age: 8.4 ± 2.66 y; range: 4-12 y), including males and females, were matched for age, gender, and body mass index (BMI). Serum samples were collected, and visfatin, resistin, and TNF-α serum levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Result. Serum visfatin, resistin, and TNF-α levels in children with ASD were significantly higher than that in the healthy patients (p < 0.05). Two significant correlations were found: a correlation between resistin and visfatin with TNF-α in children with ASD (R = 0.8 and R = 0.62, resp.) and a correlation between resistin and visfatin in children with ASD (R = 0.66). Conclusion. Higher TNF-α, resistin, and visfatin levels were found in children with ASD in comparison with controls, suggesting that elevated levels of serum proinflammatory agents may be implicated in the pathophysiology of ASD.

Association of Smoking With Semen Quality and µ-Calpain Level in Normospermia: A Case-Control Study.

OBJECTIVE: Calpains are a family of Ca(2+) dependent proteases. There is some evidence that calpains involved in fusion process that occurs between spermatozoa and the oocyte. The current study aimed to investigate the association of smoking with semen quality and µ-calpain level. MATERIALS AND METHODS: This case-control study was conducted on 117 normospermia males between June 2013 and march 2014 in Jahad Laboratory in ahvaz, Iran. The semen samples were collected from male smokers (n = 50) and non-smokers (n = 67). We divided these participants as light, moderate, or heavy smokers based on their cigarettes per day (CPD). ELISA assays were used to measure µ-calpain concentration. All semen samples were analyzed according to World Health Organization guidelines. RESULTS: The analysis of semen showed the volume, concentration, motility and morphology of semen were significantly lower among the smoker men than the non-smoker men. Also this significant difference was observed based on the number (light, moderate and heavy smokers) and duration (short term and long term smoker) of smoking. Although, showed no significant difference between µ-calpain of smoker men and non-smoker men. CPD showed negatively correlation with semen volume, concentration, motility and morphology of sperm. CONCLUSION: Sperm quality was negatively correlated with CPD and duration of smoking. However, there is no significant correlation between smoking and µ-calpain concentration.

Human Sperm Quality and Metal Toxicants: Protective Effects of some Flavonoids on Male Reproductive Function.

BACKGROUND: Metals can cause male infertility through affection of spermatogenesis and sperm quality. Strong evidences confirm that male infertility in metal-exposed humans is mediated via various mechanisms such as production of reactive oxygen species (ROS). Flavonoids have antioxidant and metal chelating properties which make them suitable candidates for neutralizing adverse effects of metals on semen quality. In the current study, we have evaluated the effects of five types of flavonoids (rutin, naringin, kaempferol, quercetin, and catechin) on recovery of sperm motility and prevention of membrane oxidative damage from aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4). MATERIALS AND METHODS: In this experimental study, motility and lipid peroxidation of metalexposed sperm was investigated in the presence of different concentrations of five kinds of flavonoids. Malondialdehyde (MDA) production was assessed as a lipid peroxidation marker. RESULTS: Aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4) diminished sperm motility. Treatment of metal-exposed sperm with rutin, naringin, and kaempferol attenuated the negative effects of the metals on sperm motility. Quercetin and catechin decreased the motility of metal-exposed sperm. CONCLUSION: Based on the MDA production results, only AlCl3 significantly induced lipid peroxidation. Treatment with rutin, naringin, and kaempferol significantly decreased MDA production.

Association of I405V polymorphism of colesteryl ester transfer protein gene with coronary artery disease in men with type 2 diabetes.

BACKGROUND: Colesteryl ester transfer protein (CETP) plays a key role in the metabolism of lipoproteins; therefore, polymorphisms of its gene can affect susceptibility to coronary artery disease (CAD) in diabetes mellitus. The aim of the present study was to investigate association between I405V polymorphism of CETP gene and risk of CAD in patients with type 2 diabetes mellitus. METHODS: The current case-control study was conducted on 143 patients with type 2 diabetes and angiographically diagnosed CAD and 150 patients with type 2 diabetes and without CAD. Genotyping was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The presence of CAD was defined as higher than 50% reduction in coronary artery diameter. RESULTS: The genotype frequencies of I405V polymorphism were II (27.3% vs. 23.2%), IV (61.5% vs. 67.5%), and VV (11.2% vs. 9.3%) in diabetic with CAD compared to diabetic without CAD (χ2 = 1.164) (P = 0.55). The I and V alleles were found at frequencies of 63.6% and 61.6% in the diabetic with CAD group and 36.4% and 38.4% in the diabetic without CAD group (χ2 = 0.263) (P = 0.60). No significant difference was observed between two groups in terms of genotype and allele frequency. Moreover, no significant association was observed between II, IV, and VV genotypes and lipid profiles in both groups. However, a significant difference was observed between genotype distributions of I405V polymorphism in men according to the severity of CAD. CONCLUSION: It is speculated that I405V polymorphism may be associated with the severity of coronary artery stenosis only in men with type 2 diabetes mellitus.

Association between two common polymorphisms (single nucleotide polymorphism -250G/A and -514C/T) of the hepatic lipase gene and coronary artery disease in type 2 diabetic patients.

BACKGROUND: Variations in the hepatic lipase (HL) gene are the potential candidate for coronary artery disease (CAD) especially in type 2 diabetes mellitus (T2DM) in diverse populations. We assessed the association of -514C/T and -250G/A polymorphisms in HL (LIPC) gene with CAD risk in Iranian population with type 2 diabetes. MATERIALS AND METHODS: We evaluated 322 type 2 diabetic patients, 166 patients with normal angiograms as controls and 156 patients those identified with CAD undergoing their first coronary angiography as CAD cases. Genotyping of -514C/T and -250G/A polymorphisms in the promoter of the LIPC gene were studied by polymerase chain reaction (PCR)-restriction fragment length polymorphism technique. RESULTS: Genotype distributions in CAD cases (73.7%, 20.5%, and 5.8% for -250G/A) and (62.2%, 32.7%, and 5.1% for -514C/T) were significantly different from those in controls (60.8%, 37.4%, and 1.8% for -250G/A) and (51.2%, 48.2%, and 0.6% for -514C/T). CAD cases had lower A-allele frequency than controls (0.131 vs. 0.196, P = 0.028). The odds ratio for the presence of -250 (GG + GA) genotype and A allele in CAD cases were 2.206 (95% confidence interval [CI] =1.33-3.65, P = 0.002) and 1.609 (95% CI = 1.051 -2.463, P = 0.029) respectively. Haplotype analysis demonstrated a significant association between especially LIPC double mutant (-250 A/-514 T) haplotype and presence of CAD. CONCLUSION: Our findings indicated that -250 G/A polymorphism rather than -514 C/T polymorphism of LIPC gene is more associated with the increased risk of CAD particularly in women with T2DM.

Association of two Common Single Nucleotide Polymorphisms (+45T/G and +276G/T) of ADIPOQ Gene with Coronary Artery Disease in Type 2 Diabetic Patients.

BACKGROUND: Adiponectin, an adipocyte-secreted hormone, is known to have anti-atherogenic, anti-inflammatory, and anti-diabetic properties. In the present study, the association between two common single nucleotide polymorphisms (SNPs) (+45T/G and +276G/T) of ADIOPQ gene and coronary artery disease (CAD) was assessed in the subjects with type 2 diabetes (T2DM). METHODS: Genotypes of two SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism in 200 subjects with T2DM (100 subjects with CAD and 100 without CAD). RESULTS: The frequency of TT genotype of +276G/T was significantly elevated in CAD compared to controls (χ2=7.967, P=0.019). A similar difference was found in the allele frequency of +276G/T between two groups (χ2=3.895, P=0.048). The increased risk of CAD was associated with +276 TT genotype when compared to reference GG genotype (OR=5.158; 95% CI=1.016-26.182, P=0.048). However, no similar difference was found in genotype and allele frequencies of SNP +45T/G between two groups. There was a CAD protective haplotype combination of +276 wild-type and +45 mutant-type allele (276G-45G) (OR=0.37, 95% CI=0.16-0.86, P=0.022) in the subject population. CONCLUSION: Our findings indicated that T allele of SNP +276G/T is more associated with the increased risk of CAD in subjects with T2DM. Also, a haplotype combination of +45G/+276G of these two SNPs has a protective effect on the risk of CAD.

Effect of ascorbic acid and alpha-tocopherol supplementations on serum leptin, tumor necrosis factor alpha, and serum amyloid A levels in individuals with type 2 diabetes mellitus.

OBJECTIVE: Diabetes mellitus Type 2 is one of the most widespread chronic metabolic diseases. In most cases, this type of diabetes is associated with alterations in levels of some inflammatory cytokines and hormones. Considering anti-inflammatory properties of plant extracts rich in ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), anti-diabetic properties of these two well-known antioxidant vitamins were investigated through measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP), insulin, leptin, tumor necrosis factor alpha (TNF-α), and serum amyloid A (SAA) in patients with diabetes mellitus type 2. MATERIALS AND METHODS: Male patients (n=80) were randomly divided into two groups each consisted of 40 subjects. Test groups were supplemented with ascorbic acid (1000 mg/day) or alpha-tocopherol (300 mg/day) orally during four weeks. Before and after treatment, serum biochemical factors of subjects were measured and compared. RESULTS: Our results showed that both ascorbic acid and alpha-tocopherol could induce significant anti-inflammatory effects by decreasing the level of inflammatory factors such as TNF-α, SAA, and hs-CRP in diabetes mellitus type 2 patients. Effects of alpha-tocopherol and ascorbic acid in decreasing serum leptin level were similar. Ascorbic acid in contrast to alpha-tocopherol diminished fasting insulin and HOMA index but had no effect on LDL serum level. CONCLUSION: Concerning the obtained results, it is concluded that consumption of supplementary vitamins C and E could decrease induced inflammatory response in patients with diabetes mellitus type 2. It is also possible that vitamin C and vitamin E supplementation can attenuate incidence of some proposed pathological effects of diabetes mellitus.

The Relationship between -2548 G/A Leptin Gene Polymorphism and Risk of Breast Cancer and Serum Leptin Levels in Ahvazian Women.

BACKGROUND: Potential association of leptin (LEP) gene polymorphisms has been suggested in the processes leading to breast cancer initiation and progression. We investigated whether genetic variations in the LEP -2548G/A gene are associated with risk of breast cancer. METHODS: This case-control study consisted of 100 breast cancer cases and 100 control subjects without breast cancer that matched for age and body mass index (BMI). Genotyping of LEP -2548G/A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Serum leptin level was determined by ELISA in all study subjects. RESULTS: The genotype distributions (AA, AG, and GG) were 36, 55, and 9% in breast cancer cases and 52, 45, and 3% in control group, respectively. The frequency of LEP -2548 GG genotype was significantly elevated in breast cancer cases as compared to controls (χ2=6.90, p=0.032). Similar difference was also found in allele frequencies between two groups (χ2=5.65, p=0.017). A markedly increase risk of breast cancer was associated with the LEP -2548GG genotype when compared to the LEP -2548 AA genotype (OR=4.33, 95% CI=1.09-17.22). In addition, postmenopausal women who bear at least one LEP -2548 G allele were at a markedly increased risk of breast cancer after adjusting for age and BMI confounders (OR=12.24, 95% CI=1.13-131.73). CONCLUSION: The LEP -2548 G/A polymorphism is associated with markedly increased risk of breast cancer especially in postmenopausal Ahvazian women and supported the hypothesis that leptin is involved in breast cancer.

Epigenetic modifications in human thyroid cancer.

Thyroid carcinoma is the most common endocrine malignancy of the endocrine organs, and its incidence rate has steadily increased over the last decade. Over 95% of thyroid carcinoma is derived from follicular cells that have a spectrum of differentiation to the most invasive malignancy. The molecular pathogenesis of thyroid cancer remains to be clarified, although activating the RET, RAS and BRAF oncogenes have been well characterized. Increasing evidence from previous studies demonstrates that acquired epigenetic abnormalities participating with genetic alteration results in altered patterns of gene expression/function. Aberrant DNA methylation has been established in the CpG regions and microRNAs (miRNAs) expression profile recognized in cancer development. In the present review, a literature review was performed using MEDLINE and PubMed with the terms 'epigenetic patterns in thyroid cancer [or papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid cancer (MTC), anaplastic thyroid cancer (ATC)]', 'DNA methylation in thyroid cancer (or PTC, FTC, MTC, ATC)', 'miRNA expression in thyroid cancer (or PTC, FTC, MTC, ATC)', 'epigenetic patterns in cancer' and the current understanding of epigenetic patterns in thyroid cancer was discussed.

Effect of leptin receptor Q223R polymorphism on breast cancer risk.

OBJECTIVES: Leptin receptor (LEPR) is a member of the class I cytokine receptor super-family that is known implicated in the initiation and progression of breast cancer. We have investigated the effect of Q223R polymorphism on the breast cancer susceptibly in a sample of Iranian subjects. MATERIALS AND METHODS: We utilized a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method to investigate the association of LEPR Q223R polymorphism with breast cancer risk in a case control study consisting of 100 breast cancer cases and 100 controls without breast cancer. Serum levels of leptin and soluble leptin receptor (sOB-R) were measured by ELISA method. RESULTS: The genotype (QQ, QR, and RR) distributions were 25, 56, and 19 % in breast cancer cases and 54, 40, and 6% in controls, respectively. The frequency of 223 RR genotype was significantly elevated in breast cancer cases as compared to controls (χ(2)= 20.072, P<0.001). Similar significance differences were also found in allele frequencies for Q and R between two groups (χ(2)= 19.027, P< 0.001). Additionally, there were significant association between Q223R genotypes and breast cancer risk; homozygotes for RR genotype (OR= 6.840; 95% confidence interval [CI] = 2.434-19.218), heterozygotes for QR (OR=3.024; 95% CI = 1.620-5.644, P = 0.001), and QR+RR genotype (OR= 3.522; 95% CI = 1.934-6.414, P < 0.001), respectively. CONCLUSION: Our results showed that the LEPR Q223R polymorphism is associated with increased breast cancer risk as well as tumor grade in a sample of Iranian subjects.

Association of CRP gene polymorphism with CRP levels and Coronary Artery Disease in Type 2 Diabetes in Ahvaz, southwest of Iran.

INTRODUCTION: We evaluated the association between four polymorphisms in the CRP gene with serum C-reactive protein (CRP) levels, prevalence and severity of coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients. METHODS: We performed coronary angiography for 308 T2DM patients and classified them into two groups: T2DM with CAD and T2DM without CAD. All patients were from Ahvaz, Iran. serum levels of CRP, glucose and lipid profile were measured. Genotyping was performed by PCR/RFLP, and the severity of coronary artery disease was determined by Gensini score. RESULTS: The GG genotype of SNP rs279421 was associated with the increased risk of CAD (OR= 2.38; 95% CI: 1.12- 5.8; p= 0.02) and CA, TT, TA genotypes and A allele of SNP rs3091244 and GA genotypes and A allele of SNP rs3093062 were significantly associated with increased CRP levels. None of genotypes or alleles was associated with Gensini score. We found that the haplotype 7 (AGCG) was associated with decreased risk of CAD (OR= 0.11; 95% CI: 0.02, 0.66; p= 0.017) and the Gensini score was correlated with increased levels of CRP, only in CAD group. CONCLUSION: Although genetic polymorphisms were influenced on serum RP levels, none of the alleles and genotypes raising or falling C-reactive protein levels was consistently associated with an increased prevalence of CAD or protected from that.

Association of serum soluble leptin receptor and leptin levels with breast cancer.

BACKGROUND: Leptin plays a key role in the regulation of energy expenditure and is known to circulate in both free and bound forms. Soluble leptin receptor (sOB-R) is a unique circulating form of leptin receptor that can bind to leptin. Leptin and leptin receptor have been implicated in processes leading to breast cancer initiation and progression. Our study was aimed to investigate the relationship between serum levels of sOB-R and leptin with breast cancer. MATERIALS AND METHODS: Serum leptin and sOB-R levels were measured by enzyme-linked immunosorbent assay in 100 women with breast cancer cases compared with 100 age and body mass index (BMI)-matched controls without cancer. Lipid profiles were measured by enzymatic method. RESULTS: The median serum levels of sOB-R in controls were significantly higher than that in breast cancer cases (odds ratio [OR], 1.98; 95% confidence interval [CI] = 0.77-188.2) versus (OR, 0.140; 95% CI = 0.09-98.1). Conversely, the median serum level of leptin in breast cancer cases was significantly higher than that in controls (OR, 67.90; 95% CI = 2.77-129.9) vs. (OR, 28.30; 95% CI = 0.60-113.1). Breast cancer was significantly associated with higher serum level of leptin (OR = 1.027, 95% CI = 1.017-1.038). Conversely, breast cancer was correlated with lower serum level of sOB-R (OR = 0.983, 95% CI = 0.969-0.997). Moreover, free leptin index (FLI) (leptin/sOB-R ratio) was associated with breast cancer (OR = 1.028, 95% CI = 1.015-1.042). The serum sOB-R level was negatively associated with leptin, BMI, and high density lipoprotein (r = -0.238, -0.186, and -0.168, respectively). CONCLUSION: Our results suggested that FLI and serum leptin level rather than serum level of sOB-R was associated with the breast cancer.

Additional effect of diabetes mellitus type 2 on the risk of coronary artery disease: role of serum adiponectin.

BACKGROUND: Adiponectin, an adipocyte-derived hormone, is implicated in diabetes mellitus type 2 and atherosclerosis. The study was designed to investigate whether serum adiponectin levels in patients with both coronary artery disease (CAD) and diabetes mellitus type 2 (T2DM) are lower than in patients with CAD alone and control subjects. OBJECTIVES: In this present study, we measured serum adiponectin levels in consecutive CAD patients with and without T2DM and investigated whether decreased adiponectin is associated with risk factors of CAD. MATERIALS AND METHODS: The study included 198 subjects, 138 patients with CAD (72 of whom had both CAD and T2DM), and 60 control subjects. We measured serum adiponectin, interleukin-6 (IL-6) and insulin by ELISA. In addition, Lipid profile, glucose and anthropometrical measurements were performed in all subjects. RESULTS: The results revealed significant difference in serum adiponectin levels between patients with CAD+T2DM and patients with CAD alone (3.80 ± 1.52 vs. 5.25 ± 2.35, P = 0.007), between patients with CAD and control (5.25 ± 2.35 vs. 7.04 ± 3.32, P = 0.001), and between patients with CAD + T2DM and control (3.80 ± 1.52 vs. 7.04 ± 3.32, P < 0.001). Serum adiponectin level was significantly higher in women in contrast to men (5.97 ± 3.15 vs. 4.62 ± 2.81 µg/ml, P = 0.002). Serum adiponectin levels were correlated significantly with insulin (r = -0.178, P = 0.013), total cholesterol (r = -0.313, P < 0.001), low density lipoprotein (r = -0.154, P = 0.016), body mass index (r = -0.171, P = 0.016), glucose (r = -0.202, P = 0.006), HOMA-IR (r= -0.251, P = 0.001), and IL-6 levels (r = -0.321, P = 0.001). Adiponectin was correlated positively only with high density lipoprotein (r = 0.389, P < 0.001). CONCLUSIONS: It is speculated that increased insulin resistance and increase in other adipokines such as IL-6 may contribute to the decreased serum levels of adiponectin in patients with both CAD and T2DM.