Nanoparticles of Selenium as Species with Stronger Physiological Effects in Sheep in Comparison with Sodium Selenite

The present study was designed to compare the effects of nano red selenium and sodium selenite on the antioxidative activities of neutrophils and the hematological parameters in sheep. Fifteen sheep were randomly allocated into three groups. Groups 1 and 2 received selenium nanoparticles orally at 1 mg/kg and sodium selenite at 1 mg Se/kg for 10 consecutive days; group 3 served as the control. To assess the degrees of oxidative stress and of lipid peroxidation of the cellular membranes, the levels of thiobarbituric acid reactive substances (TBARS) were determined in serum samples that were collected at different supplementation intervals, i.e., after 0, 10, 20, and 30 days. In addition, hematological parameters in the serum samples were measured by routine procedures. It was found that TBARS levels in groups 1 and 2 were significantly higher on days 20 and 30 compared to the basal level on day 0. It was also found that on day 30, the TBARS activities in both treated groups were significantly higher than those of the controls (P < 0.05). These findings may explain the seemingly paradoxical effects of supplemental selenium on the indicators of oxidative stress, as the levels of TBARS were generally expected to decrease in the presence of selenium. There were no significant differences between the PCV and RBC values in the three groups. The white blood cell count (WBC) in group 1 showed a significant increase on days 20 and 30 in comparison with the control group. However, in group 2, there was a significant increase of the WBC value just on day 20 in comparison with the control group. Also, there were significant increases of the neutrophil counts and significant decreases of the lymphocyte counts on day 10 in group 1, in comparison with those in group 2 and controls, and on days 20 and 30 in groups 1 and 2 in comparison with those in the control group

The Effects of Oral Consumption of Selenium Nanoparticles on Chemotactic and Respiratory Burst Activities of Neutrophils in Comparison with Sodium Selenite in Sheep

The present study was designed to compare the effects of nano-selenium and of sodium selenite on the chemotactic and respiratory burst activities of neutrophils in sheep. Fifteen sheep were randomly divided into three groups. Groups 1 and 2 received selenium nanoparticles (1 mg/kg) or sodium selenite (1 mg/kg) orally, respectively, for ten consecutive days, and the third group was considered as the control. To determine the chemotactic and respiratory burst activities of the neutrophils, the leading front assay and the NBT test were used on heparinized blood samples that were collected at different intervals (days 0, 10th, 20th, and 30th). The results obtained showed that the chemotactic activities in groups 1 and 2 increased significantly on the 10th, 20th, and 30th day, compared to day 0, and on the 20th day in comparison with the 10th day, while in group 2, there was a significant decrease on the 30th day compared to the 20th day. The chemotactic activities in group 1 were significantly higher than in group 2 on the 10th day and in the control group on the 10th, 20th, and 30th day, but the chemotactic activities in group 2 were significantly higher than those in the control group only on the 20th day. On the 30th day into the experiment, the respiratory bursts in groups 1 and 2 were significantly stronger in comparison with those at day 0. Overall, nano-selenium increased the chemotactic and respiratory burst activities more significantly than sodium selenite, which is suggestive of a stronger stimulatory effect of the Se nanoparticles on intracellular activities

International Consortium on Mammographic Density:methodology and population diversity captured across 22 countries

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses

Mammographic density and ageing:A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction

Discovery of novel hit compounds as potential HDAC1 inhibitors: The case of ligand- and structure-based virtual screening

Histone deacetylases (HDACs) as an important family of epigenetic regulatory enzymes are implicated in the onset and progression of carcinomas. As a result, HDAC inhibition has been proven as a compelling strategy for reversing the aberrant epigenetic changes associated with cancer. However, non-selective profile of most developed HDAC inhibitors (HDACIs) leads to the occurrence of various side effects, limiting their clinical utility. This evidence provides a solid ground for ongoing research aimed at identifying isoform-selective inhibitors. Among the isoforms, HDAC1 have particularly gained increased attention as a preferred target for the design of selective HDACIs. Accordingly, in this paper, we have developed a reliable virtual screening process, combining different ligand- and structure–based methods, to identify novel benzamide-based analogs with potential HDAC1 inhibitory activity. For this purpose, a focused library of 736,160 compounds from PubChem database was first compiled based on 80% structural similarity with four known benzamide-based HDAC1 inhibitors, Mocetinostat, Entinostat, Tacedinaline, and Chidamide. Our inclusive in-house 3D-QSAR model, derived from pharmacophore-based alignment, was then employed as a 3D-query to discriminate hits with the highest predicted HDAC1 inhibitory activity. The selected hits were subjected to subsequent structure-based approaches (induced-fit docking (IFD), MM-GBSA calculations and molecular dynamics (MD) simulation) to retrieve potential compounds with the highest binding affinity for HDAC1 active site. Additionally, in silico ADMET properties and PAINS filtration were also considered for selecting an enriched set of the best drug-like molecules. Finally, six top-ranked hit molecules, CID_38265326, CID_56064109, CID_8136932, CID_55802151, CID_133901641 and CID_18150975 were identified to expose the best stability profiles and binding mode in the HDAC1 active site. The IFD and MD results cooperatively confirmed the interactions of the promising selected hits with critical residues within HDAC1 active site. In summary, the presented computational approach can provide a set of guidelines for the further development of improved benzamide-based derivatives targeting HDAC1 isoform

Computer-driven development of an in silico tool for finding selective histone deacetylase 1 inhibitors

Histone deacetylases (HDACs) are a class of epigenetic modulators overexpressed in numerous types of cancers. Consequently, HDAC inhibitors (HDACIs) have emerged as promising antineoplastic agents. Unfortunately, the most developed HDACIs suffer from poor selectivity towards a specific isoform, limiting their clinical applicability. Among the isoforms, HDAC1 represents a crucial target for designing selective HDACIs, being aberrantly expressed in several malignancies. Accordingly, the development of a predictive in silico tool employing a large set of HDACIs (aminophenylbenzamide derivatives) is herein presented for the first time. Software Phase was used to derive a 3D-QSAR model, employing as alignment rule a common-features pharmacophore built on 20 highly active/selective HDAC1 inhibitors. The 3D-QSAR model was generated using 370 benzamide-based HDACIs, which yielded an excellent correlation coefficient value (R2 = 0.958) and a satisfactory predictive power (Q2 = 0.822; Q2F3 = 0.894). The model was validated (r2ext_ts = 0.794) using an external test set (113 compounds not used for generating the model), and by employing a decoys set and the receiver-operating characteristic (ROC) curve analysis, evaluating the Güner–Henry score (GH) and the enrichment factor (EF). The results confirmed a satisfactory predictive power of the 3D-QSAR model. This latter represents a useful filtering tool for screening large chemical databases, finding novel derivatives with improved HDAC1 inhibitory activity

Antibiotic resistance pattern and molecular characterization of extended-spectrum &beta;-lactamase producing enteroaggregative Escherichia coli isolates in children from southwest Iran

Mansour Amin,1,2,* Mehrandokht Sirous,2,* Hazhir Javaherizadeh,3&ndash;5 Mohammad Motamedifar,6,7 Morteza Saki,2,8 Hojat Veisi,2 Saeedeh Ebrahimi,1,9 Sakineh Seyed-Mohammadi,2,8,* Mohammad Hashemzadeh1,2 1Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Abuzar Children&rsquo;s Hospital, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 4Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Nursing Care Research Center in Chronic Diseases, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 6Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; 7Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran; 8Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 9Department of Virology, Faculty of Mdicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran *These authors contributed equally to this work Introduction: Enteroaggregative Escherichia coli (EAEC) has been implicated as an emerging cause of traveler&rsquo;s diarrhea, persistent diarrhea among children, and immunocompromised patients. The present study aimed to investigate the prevalence of antibiotic resistance, extended-spectrum &beta;-lactamase (ESBL) production, and virulence factors of EAEC isolates obtained from Iranian children suffered from diarrhea. Materials and methods: In this cross-sectional study, from March 2015 to February 2016, 32 EAEC isolates were collected from fecal samples of children aged &lt;12 years with diarrhea in southwest of Iran. All EAEC isolates identified using phenotypic and molecular methods and the cell line adhesion assay. Antimicrobial susceptibility testing was determined using disk diffusion method. The presence of virulence factors and ESBL resistance genes were determined by polymerase chain reaction. Results: Overall, 28.1% (9/32) of the isolates were positive for at least one of virulence genes. The most frequent gene was aap with a frequency of 96.9%. Neither aafA nor aggA gene was detected among all of the EAEC isolates. Antimicrobial susceptibility testing revealed the highest resistance rate to ampicillin (100%) and co-trimoxazole (100%), followed by ceftriaxone (81.3%). Further analysis revealed that the rate of ESBLs-producing isolates was 71.9% (23/32). Polymerase chain reaction screening revealed that 87.5% and 65.5% of EAEC isolates were positive for blaTEM and blaCTX-M genes, respectively, and 17 (53.1%) of isolates contained both blaTEM and blaCTX-M genes. Conclusion: The high detection rate of ESBL-producing EAEC isolates accompanied with virulence genes highlights a need to restrict infection control policies in order to prevent further dissemination of the resistant and virulent EAEC strains. Keywords: enteroaggregative Escherichia coli, diarrhea, adherence, antibiotic resistance, ESBLs, Ira