Genetic Variants of Cytochrome b-245, Alpha Polypeptide Gene and Premature Acute Myocardial Infarction Risk in An Iranian Population

Background: Oxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD) and hence acute myocardial infarction (AMI). The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, alpha polypeptide (CYBA) gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673) and premature acute myocardial infarction risk in an Iranian population. Methods: The study population consisted of 158 patients under the age of 50 years, with a diagnosis of premature AMI, and 168 age-matched controls with normal coronary angiograms. Genotyping of the polymorphisms was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: There was no association between the genotypes and allele frequencies of rs4673 polymorphism and premature acute myocardial infarction (P>0.05). A significant statistical association was observed between the genotypes distribution of rs1049255 polymorphism and AMI risk (P=0.037). Furthermore, the distribution of AA+AG/GG genotypes was found to be statistically significant between the two groups (P=0.011). Conclusions: Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI

The effects of synthetic orally administrated insulin nanoparticles in comparison to injectable insulin on the renal function markers of type 1- diabetic rats

Objective(s): Injectable insulin is the most widely used therapy in patients with type 1 diabetes which has several disadvantages. The present study was aimed to evaluate the efficacy of injectable insulin on diabetes mellitus-related complications in comparison to orally encapsulated insulin nanoparticles. Materials and Methods: This study involved 42 Wistar rats separated into 5 groups, including control (C), diabetic control (D), diabetic receiving regular insulin (INS), diabetic receiving encapsulated insulin nanoparticle (INP), and diabetic receiving chitosan for two months. Biochemical parameters in serum and urine were measured using spectrophotometric or ELISA methods. mRNA levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated using quantitative PCR. Results: There were no significant differences between the two forms of insulin in controlling the glycemic condition (P-value>0.05), but oral INP was more effective in correcting diabetic dyslipidemia in comparison to injectable insulin (P-value<0.05). Urine volume and creatinine excretion were significantly modulated by insulin and oral INP in diabetic groups (P-value<0.05), although the effects of INP on the modulation of execration of urea, acid uric, and albumin was more dramatic. Oral INP caused a significant decrease in urine concentration of KIM-1 and NGAL as well as expression of KIM-1 in renal tissue (P-value<0.05). Conclusion: Our results suggested that oral INP is more effective than injectable insulin in modulation of urine and serum diabetic-related parameters. © 2020 Mashhad University of Medical Sciences. All rights reserved

The association of plasma levels of miR-34a and miR-149 with obesity and insulin resistance in obese children and adolescents

Context. MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression that influence various cellular functions including glucose and lipid metabolism and adipocyte differentiation. Objective. The aim of this study was to evaluate the levels of miR-34a and miR-149 and their relationship with metabolic parameters in obese children and adolescents. Design. Seventy children and adolescents were enrolled in the study. Plasma levels of microRNAs were evaluated by real-time PCR using SYBR green and analyzed by �Ct method. Plasma concentrations of visfatin and insulin were measured by ELISA method. Glucose and lipid profile were determined colorimetrically. HOMA-IR was calculated and used as an index of insulin resistance (IR). Results. miR-34a was significantly lower in subjects with insulin resistance compared to obese children with normal insulin sensitivity. There was an inverse relationship between miR-34a levels and both insulin and HOMA-IR. On the other hand, miR-149 was significantly correlated with visfatin. There was no significant difference in miR-34a and miR-149 between obese and normal weight subjects. Conclusions. miR-34a is associated with insulin and HOMA-IR and thus seems to be involved in IR. miR-149 is inversely associated with visfatin levels which could be indicative of anti-inflammatory effect of this miRNA. © 2018, Acta Endocrinologica Foundation. All rights reserved

ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations

Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations; however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESCs), including a knockout and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR) and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-sequencing analyses in Zscan10−/− mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10

Water-pipe smoke condensate increases the internalization of Mycobacterium Bovis of type II alveolar epithelial cells (A549)

Background: Tuberculosis (TB) is a major global health problem, and there is an association between tobacco smoke and TB. Water pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally because users consider it as safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be a predisposing factor that enhances the incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in alveolar epithelial cells following exposure to water-pipe smoke may predispose subjects to pulmonary infection. Here, we studied the effects of water-pipe condense (WPC) on the internalization of Mycobacterium Bovis BCG by macropinocytosis in the alveolar epithelial cell line A549. Methods: A549 cells were exposed to WPC (4 mg/ml) for 24, 48, 72 and 96 h. Cell viability was studied using the methyl thiazolyldipenyl-tetrazolium bromide (MTT) reduction assay and proliferation by bromodeoxyUridine (BrdU) incorporation. Cells were exposed to FITC-Dextran (1 mg/ml) (as a control) and FITC-BCG (MOI = 10) for 20 min at 37 ° Cbeforecellswere collected and the uptake of BCG-FITC determined by flow cytometry. Similar experiments were performed at 4 ° Casacontrol . The Rho-associated protein kinase (ROCK) inhibitor Y-27632 (1 μ M) was used to assess the mechanism by which WPC enhanced BCG uptake. Results: WPC (4 mg/ml) increased the uptake of BCG-FITC after 72 (1.3 ± 0.1 fold, p < 0.05) and 96 (1.4 ± 0.05 fold, p < 0.05) hours. No effect on BCG-FITC uptake was observed at 24 or 48 h. WPC also significantly increased the uptake of FITC-Dextran (2.9 ± 0.3 fold, p < 0.05) after 24 h. WPC significantly decreased cell viability after 24 (84 ± 2%, p < 0.05), 48 (78±, 3%, p < 0.05), 72 (64 ± 2%, p < 0.05) and 96 h (45 ± 2%, p < 0.05). Y-27632 completely attenuated the increased uptake of BCG by WPC. Cell proliferation showed a decreasing trend in a time-dependent manner with WPC exposure. Conclusion: WPC exposure increased epithelial cell endocytosis activity and death as well as enhancing their capacity for macropinocytosis. Our in vitro data indicates possible harmful effects of WPC on the ability of lung epithelial cells to phagocytose mycobacterium

Decreased plasma level of TRIB3 is associated with circulating mir-124a in patients with type 2 diabetes

Background: Recent evidence indicates that TRIB3 and miR-124 levels have been deregulated in type 2 diabetes (T2D); however, the simultaneous evaluation of these markers in diabetic patients has not been investigated to date. Methods: This case-control study included 50 T2D patients and 40 age-gender matched controls. The circulation level of miR-124a was assessed by real-time PCR. TRIB3 plasma level was measured using the enzyme-linked immunosorbent assay. Results: Our findings revealed that the TRIB3 plasma level was significantly increased (p = 0.025), while miR-124a plasma levels were significantly reduced (p = 0.028) in diabetic patients compared to healthy subjects. ROC analysis showed that TRIB3 and miR-124a levels could discriminate control subjects and diabetic patients. Interestingly, a significant negative correlation was found between the TRIB3 and miR-124a plasma levels. Furthermore, there was a significant positive correlation between the TRIB3 plasma level with fasting blood glucose and insulin resistance. Conclusions: In this study, we showed deregulation of TRIB3 level in diabetic patients and its association with miR-124a circulating level and clinical parameters. These findings suggest that miR-124a may affect T2D incidence and progression by modulating the expression of TRIB3 protein level. © 2020 Verlag Klinisches Labor GmbH. All rights reserved

Assessment of Medical Science Students‘ Knowledge Regarding the Role of Nutrition in Prevention or Incidence of Cancer in Tabriz University

Background: Cancer is chronic disease that its prevalence is growing in recent years. Genetics and environmental factors such as energy balance and nutritional habits are involved in its incidence. The nutrition plays an important role in prevention and incidence of cancer due to protective and harmful factors, respectively. The aim of this study was to assess the knowledge of medical sciences students regarding the role of nutrition in prevention or incidence of cancer in Tabriz University. Methods: This Cross- sectional study conducted on 565 (219 male and 346 Female) senior students of medical sciences. A self-administered questionnaire with two part completed by students. the one was about the demographic characteristics (age, gender, course, level of education, passing nutrition unit through the school and source of nutritional information) and the other one with 22 closed and open questions was about nutritional knowledge. Data analyzed by using descriptive statistics and presented as frequency and percent. Assessment of relationship between nutritional knowledge and demographic variable were used the Pearson correlation and ANOVA. Results: About 13% of students had low level of nutritional knowledge and 41% and 45.6% had acceptable and high level of knowledge, respectively. Relationship between course, level of education, passing nutrition unit through the school and source of nutritional information of students with nutritional knowledge were statistically significant and with age and gender were no statistically significant relationship. Conclusion: Nutritional factors had important role in incidence of cancer and individual knowledge in this regard is important. In our study, medical knowledge of students, as future provider of health information hadn&acute;t adequate level, so using of efficient co-educational materials for increasing their knowledge may be beneficial