The effect of chemotherapeutic agents on telomere length maintenance in breast cancer cell lines

Copyright @ 2014 the authors. This article is made available through the Brunel Open Access Publishing Fund. It is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Mammalian telomeric DNA consists of tandem repeats of the sequence TTAGGG associated with a specialized set of proteins, known collectively as Shelterin. These telosomal proteins protect the ends of chromosomes against end-to-end fusion and degradation. Short telomeres in breast cancer cells confer telomere dysfunction and this can be related to Shelterin proteins and their level of expression in breast cancer cell lines. This study investigates whether expression of Shelterin and Shelterin-associated proteins are altered, and influence the protection and maintenance of telomeres, in breast cancer cells. 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A (TSA) were used in an attempt to reactivate the expression of silenced genes. Our studies have shown that Shelterin and Shelterin-associated genes were down-regulated in breast cancer cell lines; this may be due to epigenetic modification of DNA as the promoter region of POT1 was found to be partially methylated. Shelterin genes expression was up-regulated upon treatment of 21NT breast cancer cells with 5-aza-CdR and TSA. The telomere length of treated 21NT cells was measured by q-PCR showed an increase in telomere length at different time points. Our studies have shown that down-regulation of Shelterin genes is partially due to methylation in some epithelial breast cancer cell lines. Removal of epigenetic silencing results in up-regulation of Shelterin and Shelterin-associated genes which can then lead to telomere length elongation and stability

Effects of upper-body, lower-body, or combined resistance training on the ratio of follistatin and myostatin in middle-aged men.

PURPOSE:Due to the mechanistic role of myostatin and follistatin in modulating muscle mass, shifts in the follistatin to myostatin ratio (F:M) may help explain changes in muscular size in response to resistance training (RT). The present study examined whether differential responses in follistatin and myostatin occur based on the amount of active musculature in a RT program in middle-aged men. METHODS:Forty middle-aged men (age = 46.5 ± 3.1 years) were randomly assigned to 1 of 4 groups, upper-body RT (UB; n = 10), lower-body RT (LB; n = 10), combined RT (UB + LB; n = 10) or control (C; n = 10). The training protocol consisted of three exercise sessions per week for 8 weeks. Blood samples were obtained at baseline and 48 h after the final session of the training program. RESULTS:Muscle mass significantly increased (p < 0.05) following UB = 0.76 ± 0.46 kg, LB = 0.90 ± 0.29 kg, UB + LB = 1.38 ± 0.70 kg, compared to no changes after control. Serum follistatin increased in the LB = 0.24 ± 0.06 ng mL-1, UB = 0.27 ± 0.17 ng mL-1, UB + LB = 0.50 ± 0.18 ng mL-1, while serum myostatin decreased in the LB = - 0.11 ± 0.08 ng mL-1 and UB + LB = - 0.34 ± 0.23 ng mL-1, but not UB = 0.07 ± 0.16 ng mL-1. Further, change in concentration following training was larger between UB + LB and either LB or UB alone for both follistatin and myostatin. CONCLUSIONS:Both UB and LB increase muscle mass and alter the F: M ratio; however, the change in these endocrine markers is approximately twice as large if UB and LB is combined. The endocrine response to RT of myostatin and follistatin may depend on the volume of muscle mass activated during training

Telomere elongation in the breast cancer cell line 21NT after treatment with an epigenetic modifying drug

Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast cancer lines it has been shown that shelterin proteins are dysregulated thereby affecting the telomere stability and contributing to the neoplastic conversion of the mammary epithelial cells. Interestingly, the regulation of some of the shelterin genes is thought to be controlled epigenetically. Methods and Results: In this study, we set out to measure the effect of increased shelterin gene expression on telomere length in breast cancer cell line 21NT treated with 5-aza-2-deoxycytidine (5-aza-CdR) using known telomere length assays. We measured telomere lengths using: Telomere Restriction Fragment length (TRF), absolute quantitative-PCR and cytogenetic Interphase Quantitative Fluorescent in situ Hybridization (iQ-FISH). We found that non-cytotoxic levels of 5-aza-CdR affect telomere lengths by causing a significant and stable increase in telomere lengths of the breast cancer cell line. The increase in telomere lengths was consistently observed when various telomere length methods were used. Conclusions: Further investigation is required to understand the underlying mechanism involved, and the significance of telomere length elongation in relation to clinical outcome when epigenetic modifying drugs are utilized.We thank Professor Robert Newbold for his support and for providing the opportunity to carry out this work within the Institute of Cancer Genetics and Pharmacogenomics, Brunel University London. HY was supported by a triennial project grant (Strategic Award) from the National Centre for Replacement, Refinement, and Reduction (NC3Rs) of animals in research (NC. K500045.1 and G0800697)

EVALUATION OF ENVIRONMENTAL FACTORS IN SMART HOMES IMPLEMENTATION (CASE STUDY: CITIES OF MAZANDARAN PROVINCE IN IRAN)

The growing trend of IT technologies has continued at a faster pace in recent decades. The efforts of experts in this field have always been reducing the problems and challenges existing in urban communities and improving the quality of citizens' lives. They have concentrated on using the artificial intelligence and Internet of Things in a way which leads to maximize self-actualization of citizens. Among these technologies, IoT has played a significant role. Since it can improve the urban infrastructures, and also can be implemented in the scale of home facilities and equipment, can improve the quality of life in smart homes. However, it seems that the implementation of smart residential buildings in the context of smart cities is not simple as been defined in theory and may be accompanied by challenges. In this paper, an attempt has been made to evaluate the environmental factors affecting this field by SWOT analysis tool in a case study in cities of Mazandaran Province in Iran. As a result, strategy and tactics to emphasize strengths, to make the most of existing opportunities, to eliminate the weaknesses, and to reduce the risk of perceived threats, have been identified and been introduced. Based on the results, OS strategy should be held to obtain the most valuable goals of a smart city; since the points of opportunities and strengths are relatively more than others

Efficiency comparison of alum and ferric chloride coagulants in removal of dye and organic material from industrial wastewater - A case study

Coagulation and flocculation are most widely methods used for dye and pollution removal from various wastewaters. The aim of this study is efficiency comparison of inorganic coagulant (Alum and Ferric Cchloride) for treatment of textile factory wastewater. The appropriate coagulant was selected at optimum condition for treatment of textile's factory wastewater by measuring of dye, COD, BOD5 and TSS parameters. The different pH (4, 5, 6, 7, 8 and 9) was used for determine the optimum pH. Totally, 240 samples were collected and exanimated according the standard methods of wastewater and water tests. Results showed that the ferric chloride has more removal efficiency than alum in removal of COD, TSS and dye. The most removal of COD, TSS and dye using alum was obtained 36, 19 and 68.8 while for ferric chloride was obtained 72, 60 and 98 respectively. The optimum pH 7 and 5 were obtained for alum and ferric chloride respectively. Based on the results, it can be concluded that COD, TSS and dye removal using ferric chloride has higher efficiency than alum. Therefore, application of ferric chloride in the same conditions is preferred than alum. © 2015 Bulgarian Academy of Sciences, Union of Chemists in Bulgaria

Efficacy of tenofovir disoproxil fumarate therapy in nucleoside-analogue naive Iranian patients treated for chronic hepatitis B

Background: Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB). Objectives: To evaluate TDF efficacy in nucleos(t)ide analogues (NAs)-naive Iranian patients with CHB. Patients and Methods: The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability. Results: In all, 93 patients (64.5 hepatitis B e antigen HBeAg-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia. Conclusions: The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF. © 2015, Kowsar Corp

Diagnostic accuracy of dual-source computerized tomography coronary angiography in symptomatic patients presenting to a referral cardiovascular center during daily clinical practice

Background: There are numerous studies that address the diagnostic value of dual-source computed tomography (DSCT) as an alternative to conventional coronary angiography (CCA). However, the benefit of application of DSCT in a real world clinical setting should be evaluated. Objectives: To determine the diagnostic accuracy of DSCT technique compared with CCA as the gold standard method in detection of coronary artery stenosis among symptomatic patients who are presented to a referral cardiovascular center during daily clinical practice. Patients and Methods: Evaluating the medical records of a tertiary care referral cardiovascular center, 47 patients who had undergone DSCT and CCA, and also met the inclusion and exclusion criteria of the study were selected. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) of the DSCT imaging technique were calculated. Results: In total, 97.8 of the segments (628/642) could be visualized with diagnostic image quality via DSCT coronary angiography. The mean heart rate during DSCT was 69.2±12.2 bpm (range: 39 - 83 bpm), and the mean Agatston score was 507.7±590.5 (range: 0 - 2328). Per segment analysis of the findings revealed that the sensitivity, specificity, PPV, NPV, positive LR (PLR) and negative LR (NLR) of DSCT technique for evaluation of patients with coronary artery disease were 93.7, 96.8, 92.7, 97.2, 29.4, and 0.066, respectively. Also per vessel, analysis of the findings showed a sensitivity of 97.1, a specificity of 94.0, PPV of 95.3, NPV of 96.3, PLR of 16.1, and NLR of 0.030. Conclusion: Our results indicate that DSCT coronary angiography provides high diagnostic accuracy for the evaluation of CAD patients during daily routine practice of a referral cardiovascular setting. © 2016, Tehran University of Medical Sciences and Iranian Society of Radiology

AN EVALUATION OF LANDSLIDE SUSCEPTIBILITY MAPPING USING REMOTE SENSING DATA AND MACHINE LEARNING ALGORITHMS IN IRAN

Landslide is painstaking as one of the most prevalent and devastating forms of mass movement that affects man and his environment. The specific objective of this research paper is to investigate the application and performances of some selected machine learning algorithms (MLA) in landslide susceptibility mapping, in Dodangeh watershed, Iran. A 112 sample point of the past landslide, occurrence or inventory data was generated from the existing and field observations. In addition, fourteen landslide-conditioning parameters were derived from DEM and other topographic databases for the modelling process. These conditioning parameters include total curvature, profile curvature, plan curvature, slope, aspect, altitude, topographic wetness index (TWI), topographic roughness index (TRI), stream transport index (STI), stream power index (SPI), lithology, land use, distance to stream, distance to the fault. Meanwhile, factor analysis was employed to optimize the landslide conditioning parameters and the inventory data, by assessing the multi-collinearity effects and outlier detections respectively. The inventory data is divided into 70% (78) training dataset and 30% (34) test dataset for model validation. The receiver operating characteristics (ROC) curve or area under curve (AUC) value was used for assessing the model's performance. The findings reveal that TRI has 0.89 collinearity effect based on variance-inflated factor (VIF) and based on Gini factor optimization total curvature is not significant in the model development, therefore the two parameters are excluded from the modelling. All the selected MLAs (RF, BRT, and DT) shown promising performances on landslide susceptibility mapping in Dodangeh watershed, Iran. The ROC curve for training and validation for RF are 86% success rate and 83% prediction rate implies the best model performance compared to BRT and DT, with ROC curve of 72% and 70% prediction rate, respectively. In conclusion, RF could be the best algorithm for producing landslide susceptibility map, and such results could be adopted for the decision-making process to support land use planner for improving landslide risk assessment in similar environmental settings

Detection of pseudocyst forms of trichomonas muris in rodents from iran

Background: Trichomonas muris is one of the most common protozoa diagnosed in rodents. The trichomonads are generally described as presenting only trophozoite form while pseudocyst is another morphological form of trichomonads identified among gastrointestinal and genitourinary trichomonads. We identified and described different shapes of T. muris pseudocysts and trophozoite in stool samples were collected from rodents including Merinos persicus, Mus musculus and Cricetulus migratorius. Methods: In this cross-sectional study, stool samples from 204 trapped rodents were collected from Meshkin Shahr during Mar to Dec 2014. Samples were preserved in formalin 10 and PVA solution and transferred to Department of Medical Protozoology and Mycology, School of Public Health, Tehran University of Medical Sciences. Formalin-ether concentration method was used for the samples. The slides were stained with trichrome staining method and observed under light microscope. Results: The trophozoites were classified as T. muris based on size (18 to 24 µm), presence of three anterior flagella, recurrent flagellum, undulating membrane, and axostyle in direct examination and stained slides with trichrome staining method. Fifty-five out of 204 (27) rodents were infected with T. muris in which 51(25) samples pseudocysts form were observed. The spherical bodies of pseudocyst with almost 8 µm size, contained internalized flagella, an undulating membrane with recurrent flagellum, axostyle, and costa were seen. The pseudocysts were more prevalent than trophozoite form and pseudocysts were found with different shapes in this study. Conclusion: T. muris pseudocysts were found in stool samples of caught rodents for the first time in northwestern Iran. © 2018, Iranian Journal of Public Health. All rights reserved