The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran.

To investigate the effects of thymidylate synthase (TS) 3'UTR genotype on promotor methylation of tumor-related genes in 22 patients with sporadic colorectal cancer (CRC) from southern Iran. We evaluated the correlations of TS 3'UTR genotype with promoter methylation of hTERT, hMLH1, MSH2, MMP2, CDH1, p14, p16, and p21 genes in CRC patients. The polymorphism of TS 3'UTR was evaluated through mutagenically specific PCR. The genes promoter methylation was determined using methylation-specific PCR. For 10 patients, the gene expression profile of epigenetic regulating enzymes, histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), was also examined in both tumor and normal adjacent tissues by quantitative real time PCR. There was a significant association between the hMLH1 methylation and age of patients (P= 0.039) and also between MSH2 methylation and tumor site (P= 0.036). There was insignificant association between gene-specific methylation and TS 3'UTR genotype. However, all polymorphic genotypes of TS were associated with higher methylation of hMLH1 and CDH1 and lower methylation of MSH2. The -6bp/+6bp (heterozygous mutant) and [-6bp/+6bp, +6bp/+6bp] (homozygous mutant) genotypes resulted in higher methylation of p16, and -6bp/+6bp and [-6bp/+6bp, +6bp/+6bp] genotypes were correlated with lower methylation of MMP2. The overexpression of epigenetic enzymes, HDACs and DNMTs, was also demonstrated. There was no association between DNMTs transcript levels and gene-specific hypermethylation. The polymorphic TS genotypes, especially -6bp/+6bp, could affect methylation frequencies of studied genes. Moreover, promoter methylation status was not dependent on DNMTs gene expression. Large sample size studies may contribute to validate these findings.

Crosstalk between autophagy and insulin resistance: evidence from different tissues.

Insulin is a critical hormone that promotes energy storage in various tissues, as well as anabolic functions. Insulin resistance significantly reduces these responses, resulting in pathological conditions, such as obesity and type 2 diabetes mellitus (T2DM). The management of insulin resistance requires better knowledge of its pathophysiological mechanisms to prevent secondary complications, such as cardiovascular diseases (CVDs). Recent evidence regarding the etiological mechanisms behind insulin resistance emphasizes the role of energy imbalance and neurohormonal dysregulation, both of which are closely regulated by autophagy. Autophagy is a conserved process that maintains homeostasis in cells. Accordingly, autophagy abnormalities have been linked to a variety of metabolic disorders, including insulin resistance, T2DM, obesity, and CVDs. Thus, there may be a link between autophagy and insulin resistance. Therefore, the interaction between autophagy and insulin function will be examined in this review, particularly in insulin-responsive tissues, such as adipose tissue, liver, and skeletal muscle.

Bilirubin, an endogenous antioxidant that affects p53 protein and its downstream apoptosis/autophagy-related genes in LS180 and SW480 cell culture models of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the commonest neoplasms worldwide, which its pathogenesis is strongly correlated with p53 mutations. Antioxidants are believed to decelerate the CRC progression, possibly through interfering with p53 and its downstream target genes and mechanisms. Regarding the potential antioxidant effects of bilirubin, as an incredible endogenous antioxidant, we sought to investigate how bilirubin affected the expression levels of p53 protein and its downstream target genes, including Mdm2, Bcl-2, BECN1 and LC3, in LS180 and SW480 cell culture models of CRC. METHODS AND RESULTS: Using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide) assay, 50 and 100 µM concentrations of bilirubin were determined to be non-toxic for both LS180 and SW480 cell lines. Western blot analysis was employed to evaluate the protein expression levels of p53. The results revealed that p53 protein levels were higher in LS180 cells treated with bilirubin compared to the control group. Notwithstanding, in SW480 cells, no considerable changes were observed in p53 protein levels of treated cells compared to the control ones. The quantitative reverse transcriptase-polymerase chain reaction (q RT-PCR) method was used to measure the mRNA expression levels of the apoptosis/autophagy-related genes, Mdm2, Bcl-2, BECN1, and LC3 , as the p53's downstream target genes. Consequently, the expression of Bcl-2 and Mdm2 genes were affected by p53, while BECN1 and LC3 expression levels were decreased in both cell lines. CONCLUSION: Bilirubin is an endogenous antioxidant with significant anti-tumor effects in the studied CRC cell lines, probably through the regulation of p53 protein expression levels and subsequent control of apoptosis and autophagy, as two key processes involved in cell survival and progression of tumor cells.

Serum Copper and Zinc Levels Among Iranian Vitiligo Patients.

Introduction: Vitiligo is a chronic skin disease, which its etiopathogenesis is not fully understood. Numerous studies have suggested that oxidative stress may play a role in the pathophysiology of vitiligo. There are controversial reports as to the changes of serum trace elements, copper (Cu) and zinc (Zn) levels in vitiligo patients. Objectives: We evaluated the alterations in the level of serum Cu and Zn among a group of Iranian vitiligo patients. Methods: The levels of serum Cu and Zn were compared between 117 vitiligo patients and 137 healthy controls using atomic absorption spectrophotometry. Results: The mean Cu and Zn levels in the cases (113.57 ± 59.43 and 95.01 ± 58.95 µg/dl, respectively) were significantly lower than those of the controls (138.90 ± 38.14 and 121.83 ± 33.80 µg/dl, respectively) (P = 0.00). We also observed significantly lower serum Cu and Zn concentrations in young (< 50 years) than the elderly (≥ 50 years) patients (P = 0.00). The mean Cu and Zn levels in the patients with generalized vitiligo (111.63±54.18 and 93.11±59.33 µg/dl, respectively) were significantly lower than patients with localized vitiligo (120.74 ±71.64 and 98.69±58.63 µg/dl, respectively) and those in the control (P = 0.00). The serum Cu/Zn ratio obtained in the young and male patients was higher than those in their matched controls (P = 0.01). Conclusions: The current study has shown that the disturbance of serum Cu and Zn levels is associated with vitiligo, and may play an important role in the disease development of Iranian patients.

Apelin and its ratio to lipid factors are associated with cardiovascular diseases: A systematic review and meta-analysis.

BACKGROUND: The present systematic review and meta-analysis aimed to ascertain if the circulating levels of apelin, as an important regulator of the cardiovascular homeostasis, differ in patients with cardiovascular diseases (CVDs) and controls. METHODS: A comprehensive search was performed in electronic databases including PubMed, Scopus, EMBASE, and Web of Science to identify the studies addressing apelin in CVD up to April 5, 2021. Due to the presence of different units to measure the circulating levels of apelin across the included studies, they expressed the standardized mean difference (SMD) and their 95% confidence interval (CI) as summary effect size. A random-effects model comprising DerSimonian and Laird method was used to pool SMDs. RESULTS: Twenty-four articles (30 studies) comprised of 1793 cases and 1416 controls were included. Pooled results obtained through random-effects model indicated that apelin concentrations in the cases' blood samples were significantly lower than those of the control groups (SMD = -0.72, 95% CI: -1.25, -0.18, P = 0.009; I2 = 97.3%, P<0.001). New combined biomarkers showed a significant decrease in SMD of apelin/high-density lipoprotein cholesterol (apelin/HDL-C) ratio [-5.17; 95% CI, -8.72, -1.63, P = 0.000; I2 = 99.0%], apelin/low-density lipoprotein cholesterol (apelin/LDL-C) ratio [-4.31; 95% CI, -6.08, -2.55, P = 0.000; I2 = 98.0%] and apelin/total cholesterol (apelin/TC) ratio [-17.30; 95% CI, -22.85, -11.76, P = 0.000; I2 = 99.1%]. However, no significant differences were found in the SMD of apelin/triacylglycerol (apelin/TG) ratio in cases with CVDs compared to the control group [-2.96; 95% CI, -7.41, 1.49, P = 0.000; I2 = 99.2%]. CONCLUSION: The association of apelin with CVDs is different based on the region and disease subtypes. These findings account for the possible usefulness of apelin as an additional biomarker in the diagnosis of CVD in diabetic patients and in the diagnosis of patients with CAD. Moreover, apelin/HDL-c, apelin/LDL-c, and apelin/TC ratios could be offered as diagnostic markers for CVD.

The effect of peer education based on Pender's health promotion model on quality of life, stress management and self-efficacy of patients with multiple sclerosis: a randomized controlled clinical trial.

BACKGROUND: As a chronic, disabling disease, multiple sclerosis (MS) has challenged healthcare systems in many ways. MS adversely affects patients' quality of life and self-efficacy and results in psychological stress. The present study was conducted to investigate the effect of peer education based on Pender's health promotion model on the quality of life, stress management, and self-efficacy of patients with MS in the south of Iran. METHODS: The present study was a randomized controlled clinical trial. A total of 90 patients were divided into group A intervention group 45 patients) and group B (control group 45 patients). The intervention was peer education based on Pender's health promotion model. Data were collected using the MS Quality of Life Scale, the Self-efficacy Scale, and the Stress Management Scale. Data analyses were conducted using SPSS version 22. To analyze the data, we used descriptive statistics. Thus, inferential statistics applied included Chi-square, independent-samples t-test, and Repeated measures (ANOVA). The significance level was considered p < 0.05. RESULTS: The quality of life, self-efficacy, and stress management mean scores of the intervention group as measured immediately and 3 months after intervention were significant (p < 0.05). As for the control group, however, the difference was not significant. CONCLUSION: Peer education based on Pender's health promotion model improves patients' quality of life, stress management, and self-efficacy with multiple sclerosis. Nursing managers and health system policymakers can use this educational approach for patients with other chronic diseases to enhance their quality of life and self-efficacy. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT registration number: IRCT20190917044802N3 .

Ghrelin and ghrelin/total cholesterol ratio as independent predictors for coronary artery disease: a systematic review and meta-analysis.

The present meta-analysis aimed to summarize the available data regarding the circulating levels of ghrelin in patients with cardiovascular diseases (CVDs). A comprehensive search was performed in electronic databases including PubMed, Scopus, EMBASE, and Web of Science up to January 20, 2021. Since the circulating levels of ghrelin were measured in different units across the included studies, they were expressed as the standardized mean difference (SMD) and 95% CI (summary effect size). A random-effects model comprising the DerSimonian and Laird method was used to pool SMDs. Sixteen articles (20 studies) comprised of 1087 cases and 437 controls were included. The pooled results showed that there were no significant differences between cases and controls in terms of ghrelin levels (SMD=-0.61, 95% CI -1.38 to 0.16; p=0.120; I2=96.9%, p<0.001). The ghrelin concentrations in the CAD stratum were significantly lower than in controls, whereas they increased in other disease strata. New combined biomarkers demonstrated a significant decrease in the SMD of the ghrelin/total cholesterol (TC) ratio (-1.02; 95% CI -1.74 to -0.29, p=0.000; I2=94.5%). However, no significant differences were found in the SMD of the ghrelin/high-density lipoprotein cholesterol ratio, ghrelin/low-density lipoprotein cholesterol ratio, and ghrelin/triglyceride (TG) ratio in cases with CVDs compared with the control group. Ghrelin was associated with CAD; therefore, it may be considered a biomarker for distinguishing between patients with and without CAD. Furthermore, the ghrelin/TC ratio could be proposed as a diagnostic marker for CVD.

Blood Trace Element Status in Multiple Sclerosis: a Systematic Review and Meta-analysis.

The aim of this meta-analysis was to investigate whether the blood concentrations of patients with multiple sclerosis (MS) are associated with those of the healthy control group in terms of trace elements including zinc (Zn), iron (Fe), manganese (Mn), magnesium (Mg), selenium (Se), and copper (Cu). A comprehensive search was performed in online databases including PubMed, Scopus, Embase, and Web of Science for studies, which have addressed trace elements in MS up to July 23, 2020. The chi-square test and I2 statistic were utilized to evaluate inter-study heterogeneity across the included studies. Weighted mean differences (WMDs) and corresponding 95% CI were considered as a pooled effect size (ES). Twenty-seven articles (or 32 studies) with a total sample comprised of 2895 participants (MS patients (n = 1567) and controls (n = 1328)) were included. Pooled results using random-effects model indicated that the levels of Zn (WMD = - 7.83 mcg/dl, 95% CI = - 12.78 to - 2.87, Z = 3.09, P = 0.002), and Fe (WMD = - 13.66 mcg/dl, 95% CI = - 23.13 to - 4.19, Z = 2.83, P = 0.005) were significantly lower in MS patients than in controls. However, it was found that levels of Mn (WMD = 0.03 mcg/dl, 95% CI = 0.01 to 0.04, Z = 2.89, P = 0.004) were significantly higher in MS patients. Yet, no significant differences were observed in the levels of Mg, Se, and Cu between both groups. This meta-analysis revealed that the circulating levels of Zn and Fe were significantly lower in MS patients and that Mn level was significantly higher than those in the control group. However, it was found that there was no significant difference between MS patients and controls with regard to levels of Mg, Se, and Cu.

Toxic heavy metal concentrations in multiple sclerosis patients: A systematic review and meta-analysis.

The present meta-analysis was performed to assess the association between MS patients and control subjects in terms of their circulating levels of arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd). We searched Medline/PubMed, Scopus, Web of Science, and Embase up until June 2020 to identify all studies that examined the concentrations of heavy metals in MS patients. Statistical tests used to assess inter-study heterogeneity were Cochrane's Q test and the I2 statistic. Given the observed significant heterogeneity, the random-effects model was employed to pool the weighted mean differences (WMDs) and the corresponding 95 % confidence intervals (CIs). Out of a total of 1181 articles, 16 studies with 1650 participants (772 patients with MS and 878 controls) were included in this review meta-analysis. Pooled results using random-effects model showed that the levels of Pb (WMD= 0.73 µg/L, 95 % CI= 0.33 to 1.12, P< 0.001), As (WMD= 2.48 µg/L, 95 % CI= 1.44 to 3.53, P <0.001; I2= 98.9 %, P <0.001), and Cd (WMD= 0.17 µg/L, 95 % CI= 0.09 to 0.26, P <0.001) were significantly higher in MS patients than those of the controls. However, there were no significant differences in the levels of Hg (WMD= -0.14 µg/L, 95 % CI= -0.77 to 0.49, P= 0.658) among both groups. Sensitivity analysis indicated that after excluding one-by-one study, the overall pooled WMD of Pb was changed. This meta-analysis showed that patients with MS had significantly higher levels of circulatory As and Cd compared to the controls. Yet, there was no statistically significant difference between circulating levels of Hg and Pb among MS patients and controls. See also Figure 1(Fig. 1).

PIWI interacting RNAs perspectives: a new avenues in future cancer investigations.

As a currently identified small non-coding RNAs (ncRNAs) category, the PIWI-interacting RNAs (piRNAs) are crucial mediators of cell biology. The human genome comprises over 30.000 piRNA genes. Although considered a new field in cancer research, the piRNA pathway is shown by the existing evidence as an active pathway in a variety of different types of cancers with critical impacts on main aspects of cancer progression. Among the regulatory molecules that contribute to maintaining the dynamics of cancer cells, the P-element Induced WImpy testis (PIWI) proteins and piRNAs, as new players, have not been broadly studied so far. Therefore, the identification of cancer-related piRNAs and the assessment of target genes of piRNAs may lead to better cancer prevention and therapy strategies. This review articleaimed to highlight the role and function of piRNAs based on existing data. Understanding the role of piRNA in cancer may provide perspectives on their applications as particular biomarker signature in diagnosis in early stage, prognosis and therapeutic strategies.

Publisher Correction: Electronic Properties of Synthetic Shrimp Pathogens-derived DNA Schottky Diodes.

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Electronic Properties of Synthetic Shrimp Pathogens-derived DNA Schottky Diodes.

The exciting discovery of the semiconducting-like properties of deoxyribonucleic acid (DNA) and its potential applications in molecular genetics and diagnostics in recent times has resulted in a paradigm shift in biophysics research. Recent studies in our laboratory provide a platform towards detecting charge transfer mechanism and understanding the electronic properties of DNA based on the sequence-specific electronic response, which can be applied as an alternative to identify or detect DNA. In this study, we demonstrate a novel method for identification of DNA from different shrimp viruses and bacteria using electronic properties of DNA obtained from both negative and positive bias regions in current-voltage (I-V) profiles. Characteristic electronic properties were calculated and used for quantification and further understanding in the identification process. Aquaculture in shrimp industry is a fast-growing food sector throughout the world. However, shrimp culture in many Asian countries faced a huge economic loss due to disease outbreaks. Scientists have been using specific established methods for detecting shrimp infection, but those methods do have their significant drawbacks due to many inherent factors. As such, we believe that this simple, rapid, sensitive and cost-effective tool can be used for detection and identification of DNA from different shrimp viruses and bacteria.

A Significant Breakthrough in the Incidence of Childhood Cancers and Evaluation of its Risk Factors in Southern Iran.

BACKGROUND AND OBJECTIVE: This study investigates epidemiologic and practical information about the incidence and risk factors of childhood cancer in a population of Southern Iranian children. MATERIALS AND METHODS: A total number of 300 cancer patients along with 600 age- and gender-matched healthy control were interviewed by a trained physician regarding their demographic characteristics, and major family-associated risk factors, childhood malignancies. RESULTS: The average annual percentage change for cancers in the studied population is calculated as 45%. Our study indicated that possible risk factors which could contribute to the development of childhood cancer are maternal oral contraceptive pill use during pregnancy, exposure to radiation during pregnancy, parental smoking, residence near high voltage electricity lines, exposure to pesticides and fertilizers, patient allergy, contact with domestic animals and father's educational degree. Furthermore, new ecological risk factors such as air pollution due to nonstandard petroleum or toxic inhalant particles, nonhealthy food consumption, and satellite jamming are other predisposing factors. CONCLUSION: Our study reported a higher average annual percentage change of childhood cancers in our area, compared to the existing literature. In conclusion, detection and prevention of the consistent and possible new environmental risk factors such as nonstandard petroleum or satellite jamming from all around the country should be taking into consideration.