Prevalence and Risk Factors of Anemia in the MASHAD Cohort Study.

BACKGROUND: Anemia is a serious public health problem which may be associated with cardiovascular diseases (CVDs) and brain damage. This survey aims to determine the prevalence of anemia and its association with demographic and biochemical factors and metabolic syndrome in a human sample derived from the MASHAD cohort study. METHODS: This survey was conducted on a sub-sample of 9847 individuals aged 35 to 65 as part of the MASHAD cohort study. Demographic characteristics and biochemical and anthropometrics indices were recorded. Data were analyzed using SPSS version 20. RESULTS: Anemia was seen in 11.5% of the population. Anemia was significantly more prevalent in younger subject (P<0.001), females (P<0.001) and those with elevated body mass index (BMI) (P<0.001). Mean high-density lipoprotein (HDL) was higher in anemic participant (P=0.032). The incidence of anemia was significantly lower in smokers (P<0.001) and also participant with hypertension (HTN) (P<0.001), diabetes mellitus (DM) (P<0.001) and metabolic syndrome (MetS) (P<0.001). Mean FBG (P<0.001), TG (P<0.001), total cholesterol (P<0.001), LDL (P<0.001) and uric acid (P<0.001) were significantly lower in anemic subjects. Cholesterol, MetS, low-density lipoprotein (LDL), BMI, uric acid, diabetes mellitus and also TG remained significantly different after multivariate analysis between anemic and healthy participants. CONCLUSION: The studied population had a lower prevalence of anemia compared to the previous WHO report for Iranians. Iron deficiency is recognized as the most important cause of anemia in Iran; however, further investigations will be need to confirm this pattern. We demonstrated that anemia is adversely associated with MetS and DM.

Association of cyclin-dependent kinase inhibitor 2A/B with increased risk of developing breast cancer.

There is a growing body of data reporting the association of genetic alterations in chromosome 9P21 with the risk of developing cancer. In the current study, we studied the association of a genetic variant in CDKN2A/B, rs1333049, with the risk of developing breast cancer. A total of 339 participants with and without breast cancer entered to the study. Genotyping was done by the TaqMan real-time polymerase chain reaction (RT-PCR) method and gene expression analysis was ran by RT-PCR. Our data showed that the minor allele homozygote in the total population was 10%, whereas for heterozygote was 38%. The dominant genetic model demonstrated that individuals with breast cancer had advanced TNM classification. Moreover, the logistic regression revealed that individuals who had CC/CG genotypes might have an enhanced risk of developing breast cancer when compared to the holders of GG genotype (e.g., OR = 2.8; 95% CI,1.4-5.4; p = .001), after regulated for confounders; age and body mass index. Furthermore, our analysis showed that the CDKN2A/B gene was downregulated in patients (p < .001). We showed a meaningful relationship of CDKN2A/B with the risk of breast cancer, cancer, showing the importance of studies in great sample size and several centers for studying the value of the marker as a risk classification in the management of patients with breast cancer.

Vitamin D in inflammatory bowel disease: From biology to clinical implications.

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract consisting two principal categories, ulcerative colitis (UC) and Crohn's disease (CD). The precise etiology of IBD remains unknown. Vitamin D is an important micronutrient that plays a critical biological role in various processes in human tissues. However, the relationship between disruption of the gut microbiota and the development of IBD is unclear. Some studies suggest that IBD is the cause of disrupted gut microbiota while others propose that gut microbiota itself can lead to development of IBD. Regardless of this complexity, it has emerged that vitamin D is an immunoregulatory factor that plays a significant role in the pathogenesis of IBD by affecting the gut microbiome and the inflammatory response. It has been reported that 38.1% of CD patients and 31.6% of UC patients suffer from vitamin D deficiency (VDD). In this review, we aimed to evaluate the association between VDD and IBD, summarizing recent clinical studies examining the effect of low vitamin D and the role of vitamin D supplementation on IBD clinical outcomes.

Circulating and Tissue microRNAs as Biomarkers for Ovarian Cancer Prognosis.

Ovarian cancer (OC) is one of the most common cancers globally with a high rate of cancer- associated mortality. OC may be classified into epithelial cell neoplasms, germ cell neoplasms and stromal cell neoplasms. The five-year survival in the early and advanced stages of disease is approximately 90% and 15%, respectively. microRNAs are short, single-stranded, non-coding ribonucleic acid (RNA). miRNAs play critical roles in post transcriptionally regulations of gene expression. miRNAs are found in different tissues and body fluids. In carcinogenesis the expression of miRNAs are altered. Recent studies have revealed that there is a relationship between alteration of miRNAs expression and the prognosis of patients with OC. The aim of this review was to summarize the findings of recent studies that have investigated the expression of circulating and tissue miRNAs as novel biomarkers in the prognosis of OC.

Personalized Peptide-based Vaccination for Treatment of Colorectal Cancer: Rational and Progress.

Colorectal cancer (CRC) is one of the most common cancers globally and is associated with a high rate of morbidity and mortality. A large proportion of patients with early stage CRC, who undergo conventional treatments develop local recurrence or distant metastasis and in this group of advanced disease, the survival rate is low. Furthermore there is often a poor response and/or toxicity associated with chemotherapy and chemo-resistance may limit continuing conventional treatment alone. Choosing novel and targeted therapeutic approaches based on clinicopathological and molecular features of tumors in combination with conventional therapeutic approach could be used to eradicate residual micrometastasis and therefore improve patient prognosis and also be used preventively. Peptide- based vaccination therapy is one class of cancer treatment that could be used to induce tumorspecific immune responses, through the recognition of specific antigen-derived peptides in tumor cells, and this has emerged as a promising anti-cancer therapeutic strategy. The aim of this review was to summarize the main findings of recent studies in exciting field of peptide-based vaccination therapy in CRC patients as a novel therapeutic approach in the treatment of CRC.

HSP27 expression in the human peripheral blood mononuclear cells as an early prognostic biomarker in coronary artery disease patients.

BACKGROUND: Coronary artery disease (CAD), is one of the leading causes of death globally. CAD risk factors, such as smoking, dyslipidemia, and obesity, are mainly associated with increased oxidative stress. Heat Shock Protein-27 (HSP27) has a protective role in conditions of oxidative stress. The aim of the current study was to investigate the relationship between HSP27 mRNA copy numbers in the peripheral blood mononuclear cell (PBMCs) and the degree of CAD progression. METHODS: A total of 103 subjects aged 49-71 years were recruited; Patients with CAD were categorized into two groups: patients having <50% stenosis (Angio-) and ≥50% stenosis (Angio+). The mRNA copy numbers of HSP-27 in PBMCs, anthropometric-parameters, fasting blood glucose (FBG), and the fasted serum lipid profile were evaluated. RESULTS: Angio+ patients had a significantly higher level of TC and LDL-C values compared with Angio- patients and the control group (p < 0.05). The HSP27 expression in PBMCs was significantly increased in Angio+ and Angio- subjects, compared to the control group. Moreover, there was a significant association between the FBG, TC, LDL-C and TG among the groups (p < 0.05). CONCLUSION: It was shown that the increased expression of HSP27 in PBMCs of CAD patients is significantly correlated with CAD severity in Angio+ subjects, which can be used as an early prognostic biomarker, indicating the degree of overall oxidative stress in patients. In order to verify this statement, it is suggested to measure Pro-oxidant- Antioxidant Balance (PAB) test by the same design in subsequent studies.

The potential therapeutic and prognostic impacts of the c-MET/HGF signaling pathway in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and a common cause of cancer-related mortality globally. In spite of the improvements in the early diagnosis of CRC, approximately one-third of patients develop metastasis and then have a very poor survival rate. The mesenchymal-epithelial transition factor (c-MET) is a tyrosine kinase cell surface receptor activated by hepatocyte growth factor (HGF). Activation of c-MET/HGF signaling pathway regulates a variety of biological processes including cell motility, cell proliferation, angiogenesis, the epithelial-to-mesenchymal transition, and the development and progression of cancer cells. Recent studies have suggested that the c-MET/HGF signaling pathway is involved in the carcinogenesis of CRC. In this review, we summarize the main findings of recent studies investigating the role of c-MET/HGF signaling pathway in CRC and the potential of the c-MET/HGF signaling pathways in the diagnosis and treatment of CRC. © 2019 IUBMB Life, 2019.

MicroRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common cancer, and the second most common cause of cancer-associated death globally. One of the major reasons for this high rate of mortality is a failure to make an early diagnosis. The average survival in untreated HCC patients is estimated to be approximately three months. The 5-year overall survival rate after radical resection is about 15-40% and within two years, more than two third of patients experience a relapse. To date, the most common biomarker which has been used for the diagnosis of HCC is serum alpha-fetoprotein (AFP). However, there is a lack of sensitive and specific tumor biomarkers for the early diagnosis of HCC. MicroRNAs are a class of short endogenous RNA with crucial role in many biological activities and cellular pathways and can be found in various tissues and body fluids. The aim of this review was to summarize the results of recent studies investigating miRNAs as novel biomarkers for the early diagnosis and prognostic risk stratification of patients with this type of liver cancer.

Targeting cancer stem cells as therapeutic approach in the treatment of colorectal cancer.

Colorectal cancer is one of the most common cancers globally. A large portion of colorectal cancer patients who are treated with conventional chemotherapy eventually develop local recurrence or metastases. The failure of a complete cure in colorectal cancer patients may be related to the lack of complete eradication of cancer stem cells when using conventional therapy. Colorectal cancer stem cells comprise a small population of tumor cells that possess the properties of rapid proliferation and differentiation. The colorectal cancer stem cells are also phenotypically and molecularly distinct, and resistant to conventional chemo-radiotherapy. Therefore, it is important to identify approaches in combination with conventional therapy for targeting and eradicating cancer cells. The aim of this review was to summarize the main findings of recent studies on targeting colorectal cancer stem cells as a novel therapeutic approach in colorectal cancer treatment.

Differential expression of alternative transcripts of soluble guanylyl cyclase, GYCY1a3 and GUCY1b3 genes, in the malignant and benign breast tumors.

Extensive alterations in splicing is one of the molecular indicator for human cancers. Soluble guanylyl cyclase (sGC), an obligatory heterodimer, is composed of α1 and ß1 subunits. Each subunit is encoded by a separate gene, GUCY1a3 and GUCY1b3, correspondingly. sGC activity has been regulated by an alternative splicing and it has an important effect on the breast cancer. sGC alternative splicing has been evaluated in the 55 malignant, 25 benign and 30 normal breast tissues using qRT-PCR and RT-PCR. The differences between groups were analyzed by Mann-Whitney U. The expression of six different splice forms have been detected, three for α1 and three for ß1 sGC. Expressions of Tr1, Tr2 ß1 sGC and Tr7, Tr6 α1 sGC mRNA in the malignant breast tumors were significantly lower than those of benign and normal breast tissues. However, the expression of Tr3 α1 sGC mRNA was significantly higher than that of benign and normal tissues. Present data have provided some evidences for an alteration in the expression of α1 and ß1 sGC alternative splicing forms which may contribute to the loss of sGC functions in the breast cancer. The observed information might be discussed by the cGMP status.

Circulating Exosomes as Potential Biomarkers in Cardiovascular Disease.

Cardiovascular disease (CVD) is the first leading cause of morbidity and mortality in developing and developed countries. Circulating exosomes have recently been identified as extracellular transporters, detectable in biological fluids. Exosomes have established a new era in diagnosing diseases, especially CVD. Determination of exosome profiles, e.g., miRNAs, for different health states such as myocardial injury still requires further studies. In this review, we will discuss the role of exosomes as a potential biomarker in CVD, with particular emphasis on recent advances in the methods to study exosomes, isolation, detection, and characterization.

The effects of curcumin and a modified curcumin formulation on serum Cholesteryl Ester Transfer Protein concentrations in patients with metabolic syndrome: A randomized, placebo-controlled clinical trial.

OBJECTIVE: Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl ester from HDL-C to LDL-C and VLDL-C. The aim of the present trial was to evaluate the effect of curcumin and its modified formulation on serum CETP concentrations in patients with metabolic syndrome. MATERIALS AND METHODS: Participants were randomly allocated to one of three groups of 40 subjects receiving either unmodified curcumin or its phospholipid complex or placebo. Lipid profile and plasma CETP were measured at the start and six weeks after initiation of the treatment. The normality of data distribution was assessed by Kolmogorov-Smirnov test. Wilcoxon test was used for comparing the data before and after the intervention. The percent changes of CETP and biochemical factors among the three groups were compared using Kruskal-Wallis test. RESULTS: Serum CETP levels were not significantly altered among patients receiving curcumin. CONCLUSION: Curcumin and its complex had no significant effect on serum CETP concentrations.

Epigenetic Drug Therapy in the Treatment of Colorectal Cancer.

Colorectal Cancer (CRC) is one of the most common cancers with a high rate of morbidity and mortality worldwide. It has been demonstrated that epigenetic alterations which may cause changes in the expression of microRNA, DNA methylation and histone acetylation that results in inheritable modifications in gene expression in colorectal epithelial cells, plays a crucial role in the development of CRC. Recently, targeting epigenetic modification has emerged as a potentially important treatment approach in CRC. The US Food and Drug Association has approved the use of some epigenetic drugs that may be able to inhibit or reverse these alterations and also enhance sensitivity to chemotherapeutic agents and radiotherapy in CRC. In this review we have summarized the recent pre-clinical and clinical trial studies investigating the therapeutic value of using epigenetic drugs as novel therapeutic approach in CRC treatment.

Hookah smoking is strongly associated with diabetes mellitus, metabolic syndrome and obesity: a population-based study.

OBJECTIVES: The adverse effects of cigarette smoking have been widely studied before, whilst the effects of hookah smoking has received less attention, although it is a common habit in the Middle East. Here we have investigated the effects of cigarette and hookah smoking on biochemical characteristics in a representative population sample derived from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study, from Northeastern Iran. STUDY DESIGN: A total of 9840 subjects from the MASHAD population study were allocated to five groups; non-smokers (6742), ex-smokers (976), cigarette smokers (864), hookah smokers (1067), concomitant cigarette and hookah smokers (41). METHODS: Baseline characteristics were recorded in a questionnaire. Biochemical characteristics were measured by routine methods. Data were analyzed using SPSS software and p < 0.05 was considered significant. RESULTS: After adjustment for age and sex; the presence of CVD, obesity, metabolic syndrome, DM and dyslipidemia were significantly (p < 0.001) related to smoking status. After multivariate analysis, HDL (p < 0.001), WBC (p < 0.001), MCV (p < 0.05), PLT (p < 0.01) and RDW (p < 0.001), and the presence of CVD (p < 0.01), obesity (p < 0.001), metabolic syndrome (p < 0.05) and DM (p < 0.01) remained significant between cigarette smokers and non-smokers. Between hookah smokers and non-smokers; uric acid (p < 0.001), PLT (p < 0.05) and RDW (p < 0.05), and the presence of obesity (p < 0.01), metabolic syndrome (p < 0.001), diabetes (p < 0.01) and dyslipidemia (p < 0.01) remained significant after logistic regression. CONCLUSION: There was a positive association between hookah smoking and metabolic syndrome, diabetes, obesity and dyslipidemia which was not established in cigarette smoking.

Interaction between a variant of CDKN2A/B-gene with lifestyle factors in determining dyslipidemia and estimated cardiovascular risk: A step toward personalized nutrition.

BACKGROUND & AIMS: Several genome-wide-association-studies have identified genetic variants in a region on chromosome 9p21 that are associated with an increased risk of Cardiovascular disease (CVD) and diabetes. Here we have explored the interaction of a genetic variant of the CDKN2A/B-rs10811661 gene locus with cardiovascular risk factors and environmental-exposures (e.g., diet and physical activity) in 1165 individuals recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders cohort. METHODS: Genotyping was carried out using TaqMan-real-time-PCR based method. The association of CDKN2A/B-rs10811661 locus and its interaction with dietary intake in association with the main determinants of dyslipidemia, and cardiovascular-risk-factors were assessed in 2 cohorts. RESULTS: Our data showed that obese subjects with a TT genotype had a higher level of TG, TG/HDL ratio and Hs-CRP, compared to the subjects with the wild type genotype, or individuals with a normal BMI. Moreover, the presence of a TT genotype was associated with increased risk of hypercholesterolemia, insulin resistance and CVD. These effects were more pronounced in the sub-group with low physical activity and a high dietary energy intake (e.g., the interaction between TT genotype and total energy intake on serum cholesterol was positive (RERI: 0.2, 95%CI (-0.96-1.3), AP: 0.1, 95%CI (-0.5-0.7) and SI: 1.2, 95%CI (0.3-5.1))). CONCLUSIONS: We have found a significant association between the CDKN2A-rs10811661 polymorphism with cardiovascular risk factors and dyslipidemia in a non-diabetic population. It is possible that a low energy diet and high physical activity could ameliorate the unfavorable effects of T allele of CDKN2A/B locus. Functional analysis is warranted to investigate the value of this genetic biomarker of CVD risk in obese people.

The diagnostic and prognostic value of circulating microRNAs in coronary artery disease: A novel approach to disease diagnosis of stable CAD and acute coronary syndrome.

Coronary artery disease (CAD) is the most common manifestation of CVD and the acute coronary syndrome (ACS) is associated with a substantial morbidity and mortality in most populations globally. There are several biomarkers for diagnosis of MI. Troponin is routinely used as a biomarker in patients with chest pain, but it lacks sensitivity in the first hours of onset of symptoms, and so there is still a clinical need for new biomarkers for the diagnosis of CAD events. Recent studies have shown that miRNAs are involved in atherosclerotic plaque formation and their expression is altered during CAD events. Whilst studies have shown that several miRNAs are not superior to troponin in the diagnosis of a MI, they may be useful in the early diagnosis and prognosis of patients with CAD, however further studies are required. In this review we have summarized the recent studies investigating circulating miRNAs as novel biomarkers for the early detection of MI, CVD risk stratification and in the assessment of the prognosis of patients with ACS.

The interaction between a HSP-70 gene variant with dietary calories in determining serum markers of inflammation and cardiovascular risk.

BACKGROUND: The high prevalence of cardiovascular disease (CVD) globally is attributable to an interaction between environmental and genetic factors. Gene × diet interaction studies aim to explore how a modifiable factor interacts with genetic predispositions. Here we have explored the interaction of a heat shock protein (HSP70) gene polymorphism (+1267A > G) with dietary intake and their possible association with serum C-reactive protein (CRP), an inflammatory marker, that is a major component of CVD risk. METHODS: HSP70 genotype was determined using a TaqMan real time PCR based method.Dietary intake was assessed using a dietary questionnaire. Serum high sensitivity (Hs) CRP and other cardiovascular risk factors were assessed by routine methods. This included coronary angioplasty to determine the presence of coronary artery stenosis. RESULTS: There were significant differences between serum lipid profile and Hs-CRP across the genotypes for Hsp70. The carriers of G allele had higher serum hs-CRP concentrations, compared with the AA homozygotes, with the wild genotype. Interaction analysis showed the association was modulated by total energy intake; the interaction of high energy intake with GG genotype: RERI = 0.77, AP = 0.26, S = 1.6. CONCLUSION: We have found a significant association between the +1267A > G variant of the HSP70 gene with cardiovascular risk factors and serum hs-CRP concentrations. It is possible that a low energy diet could ameliorate the unfavorable effects of G allele of HSP70.

Relationship between serum anti-heat shock protein 27 antibody levels and obesity.

BACKGROUND: Heat shock protein 27 (HSP27) is an intracellular molecular chaperone that is expressed at high levels following the exposure of cells to environmental stressors such as heat, toxins, and free radicals. High levels of HSP antigens and antibody titers have been reported in several conditions including cardiovascular disease and cancers. We measured serum anti-HSP27 antibody levels in 993 subjects and assessed the associations between serum anti-HSP27 antibody levels and demographic characteristics including coronary risk factors. METHODS: A total of 993 subjects were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. Demographic, clinical, and biochemical parameters and serum anti-HSP27 antibody titers were determined in all the subjects. RESULTS: Serum anti-HSP27 antibody levels increased with increasing age in men. No significant differences in levels were detected between men and women. Serum anti-HSP27 antibody levels were significantly higher in obese subjects than in nonobese subjects (P=0.046); however, no significant influence of smoking status was observed. Moreover, serum anti-HSP27 antibody titers were positively associated with age, body mass index, waist/hip ratio, the presence of diabetes mellitus, nonsmoking habit, serum triglycerides, cholesterol, and high-sensitivity c-reactive protein. CONCLUSION: We have found that serum anti-HSP27 antibody titers are related to several cardiovascular risk factors, necessitating further studies on the value of this emerging marker for risk stratification.

The application of a decision tree to establish the parameters associated with hypertension.

INTRODUCTION: Hypertension is an important risk factor for cardiovascular disease (CVD). The goal of this study was to establish the factors associated with hypertension by using a decision-tree algorithm as a supervised classification method of data mining. METHODS: Data from a cross-sectional study were used in this study. A total of 9078 subjects who met the inclusion criteria were recruited. 70% of these subjects (6358 cases) were randomly allocated to the training dataset for the constructing of the decision-tree. The remaining 30% (2720 cases) were used as the testing dataset to evaluate the performance of decision-tree. Two models were evaluated in this study. In model I, age, gender, body mass index, marital status, level of education, occupation status, depression and anxiety status, physical activity level, smoking status, LDL, TG, TC, FBG, uric acid and hs-CRP were considered as input variables and in model II, age, gender, WBC, RBC, HGB, HCT MCV, MCH, PLT, RDW and PDW were considered as input variables. The validation of the model was assessed by constructing a receiver operating characteristic (ROC) curve. RESULTS: The prevalence rates of hypertension were 32% in our population. For the decision-tree model I, the accuracy, sensitivity, specificity and area under the ROC curve (AUC) value for identifying the related risk factors of hypertension were 73%, 63%, 77% and 0.72, respectively. The corresponding values for model II were 70%, 61%, 74% and 0.68, respectively. CONCLUSION: We have developed a decision tree model to identify the risk factors associated with hypertension that maybe used to develop programs for hypertension management.

Nutrient patterns and their relationship to metabolic syndrome in Iranian adults.

BACKGROUND: The prevalence of metabolic syndrome (MetS) is increasing globally. It is associated with a significant risk of developing type 2 diabetes mellitus and cardiovascular disease. MATERIALS AND METHODS: The relationship between adherence to several different dietary patterns and the presence of MetS was explored in an Iranian population sample of 5764 subjects. RESULTS: We observed that the prevalence of MetS was 13% and 18% in men and women, respectively. There were three main dietary patterns: the first pattern was characterized by protein, carbohydrate, starch, glucose, fructose, sucrose, maltose, dietary fibre, potassium, calcium, magnesium, phosphorus, iron, zinc, manganese, thiamine, riboflavin, carotene, vitamin c and lactose; second representative of fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, sodium, calcium, zinc, phosphorus, iodine, vitamin D, chloride, betaine, niacin; third consisting of copper, selenium, vitamin A, riboflavin, vitamin B12. In this dietary pattern, individuals in first quintile had a higher consumption of total fat, saturated fatty acid, monounsaturated fatty acid, polyunsaturated fatty acid, cholesterol and vitamin A. In the second pattern, individuals in the fifth quintile ate less carbohydrate, dietary fibre, glucose, Fructose, potassium compared to first quintile. We found that individuals in the first quintile in pattern 3 had higher intakes of protein, zinc and calcium compared to other quintiles. CONCLUSIONS: We have found that a nutrient pattern which mostly characterized by dietary protein, carbohydrate, starch, glucose, fructose, sucrose, maltose was associated with a higher risk of MetS in both genders, while a pattern which was represent of copper, selenium, Vitamin A, riboflavin, vitamin B12 was associated with greater odds of Mets, in women.