Nonylphenol induces proliferation of prostate epithelial cell line (PNT1a)

Nonylphenol (NP) belongs to Endocrine Disrupting Chemicals (EDCs) with xenoestrogenic activity, called xenoestrogens, abundantly present in the environment. NP is widely used as surfactants in industrial and agricultural applications and in plastic formulations. Its xenoestrogenic activity was demonstrated both in vitro and in vivo. However, there are only few studies on the NP effects on prostate cell lines. Estrogens play an important role in development and growth of the prostate and may cause some pathologies, including cancer. Since NP mimics endogenous estrogens, it could have a negative influence on prostate physiology. In this study we examined the effects of NP and 17β-estradiol (E2) on the proliferation of non tumorigenic prostate epithelial cell line (PNT1A) and their interaction with estrogen receptors. These effects were also studied in presence of selective estrogen receptor antagonist ICI182,780. We found that both NP and E2 stimulate PNT1A proliferation in a dose-dependent manner, but the NP effects were lower than E2. Immunofluorescence and western blot analyses revealed that both NP and E2 induce cytoplasm-nucleus translocation of ERα. The nuclear localization of ERα by E2 was already shown after 2h of treatment and only after 6h by NP. The inhibition of these effects by adding ICI182,780 was shown. Surprisingly, NP and E2 didn’t affect the localization of ERβ. These results suggest that NP stimulates PNT1A proliferation probably through the interaction with ERα that in turn is involved in the activation of some prostate cell cycle key regulators

Candida albicans identification: comparison among nine phenotypic systems and a multiplex PCR

Background. Candida albicans is the most common fungal pathogen isolated from clinical samples and is also the most common yeast species carried as a commensal by healthy individuals although some non-C. albicans species account for an important number of infections. Objectives. To compare nine phenotypic systems for C. albicans identification [API 20C AUX; RapID Yeast Identification panel (RYIP); Vitek2 ID-YST system; chromogenic media, CHROMagar, Oxoid Chromogenic Candida Agar (OCCA), Candida ID2, Candida Identification Agar, CandiSelect 4, and Chromalbicans Agar] with multiplex PCR. Patients/Methods. A collection of 390 yeast strains was obtained by routine isolation from oral and vaginal swabs. All of the yeasts isolated were tested for germ tube formation, and then submitted to a multiplex PCR protocol tested in previous studies, and to nine phenotypical commercial methods, together with the reference ATCC strains. Comparison was limited to the ability of the tests to identify C. albicans. Results. 253 isolates were provisionally identified as C. albicans by germ tube, and their identities were further confirmed with the multiplex PCR. Sensitivity of phenotypical systems ranged from 81.9% (Vitek2) to 87.7% (Candida ID2 e CHROMagar). For specificity, the highest value was 96.8% for Candida ID2, and the lowest value (75.1%) was for Chromalbicans Agar. Conclusions. Although with differences in discriminatory power, the methods tested showed overall acceptable levels of sensitivity and specificity respect to the multiplex PCR; therefore, all could be useful for C. albicans identification where molecular differentiation is not available

Small leucine rich proteoglycans are differently distributed in normal and pathological endometrium

BACKGROUND: During the woman's fertile period, the non-pregnant uterus is subject to constant cyclic changes. The complex mechanisms that control the balance among proliferation, differentiation, cell death and the structural remodeling of the extracellular matrix can contribute to the benign or malignant endometrial pathological state. The small leucine-rich proteoglycans (SLRPs) are important components of cell surface and extracellular matrices. MATERIALS AND METHODS: Using immunohistochemistry, we showed that the distribution patterns of SLRPs were completely modified in the pathological compared to normal endometrium. RESULTS: The expression of SLRPs was low/absent in all endometrial pathologies examined compared to normal endometrium. We observed an increase of lumican from proliferative to secretory phase of the endometrium and a decrease of fibromodulin, biglycan and decorin. In menopause endometrial tissue, the level of expression of fibromodulin, biglycan, decorin and lumican dramatically decreased. CONCLUSION: The results revealed the prominence and importance of proteoglycans in the tissue architecture and extracellular matrix organization

Antioxidant Supplementation Hinders the Role of Exercise Training as a Natural Activator of SIRT1

Exercise training (ET) is a natural activator of silent mating type information regulation 2 homolog 1 (SIRT1), a stress-sensor able to increase the endogenous antioxidant system. SIRT1 activators include polyphenols and vitamins, the antioxidant properties of which are well-known. Antioxidant supplements are used to improve athletic performance. However, they might blunt ET-related benefits. Middle-distance runners (MDR) taking (MDR-S) or not taking antioxidant supplements (MDR-NoS) were compared with each other and with sedentary subjects (CTR) to evaluate the ET effects on SIRT1 levels and oxidative stress, and to investigate whether an exogenous source of antioxidants could interfere with such effects. Thirty-two MDR and 14 CTR were enrolled. MDR-S took 240 mg vitamin C and 15 mg vitamin E together with mineral salts. SIRT1 mRNA and activity were measured in PBMCs. Total oxidative status (TOS) and total antioxidant capacity (TEAC) were determined in plasma. MDR showed higher levels of SIRT1 mRNA (p = 0.0387) and activity (p = 0.0055) than did CTR. MDR-NoS also showed higher levels than did MDR-S without reaching statistical significance. SIRT1 activity was higher (p = 0.0012) in MDR-NoS (1909 ± 626) than in MDR-S (1276 ± 474). TOS did not differ among the groups, while MDR showed higher TEAC levels than did CTR (2866 ± 581 vs. 2082 ± 560, p = 0.0001) as did MDR-S (2784 ± 643) and MDR-NoS (2919 ± 551) (MDR-S vs. CTR, p = 0.0007 and MDR-NoS vs. CTR, p = 0.003). TEAC (β = 0.4488356, 95% CI 0.2074645 0.6902067; p < 0.0001) and the MDR-NoS group (β = 744.6433, 95% CI 169.9954 1319.291; p= 0.012) predicted SIRT1 activity levels. Antioxidant supplementation seems to hinder the role of ET as a natural activator of SIRT1

Triclosan and estradiol effects on human prostate cells

Xenoestrogens are estrogen-mimicking compounds that are commonly found in personal care products and pesticides. The activity of xenoestrogens in the human body involves interference with estrogen receptor binding. Triclosan (TCS), a lesserknown xenoestrogen, is a broad-spectrum antibacterial commonly used in cosmetics, toothpastes, soap and other consumer products. The widespread use of TCS and its detection in human breast milk, urine and serum have raised concerns regarding its association with various health outcomes. Recent evidence suggests that TCS may play a role in cancer development, perhaps through its estrogenicity. In the present work we have studied the effects of TCS and Estrogen (E2) on human prostate adenocarcinoma epithelial cells (LNCaP) in order to highlight estrogen and xenoestrogen influence on human prostate. Although androgens are the most important hormones in the normal development of the male reproductive system, more recently, it has been suggested a central role for estrogen in male reproductive system and it has been hypothesized that high level of estrogens may disturb the endocrine control of the male reproductive capability. We examined the effects of TCS and E2 on the proliferation of the LNCaP through MTT assay. They were both able to increase cell proliferation at concentration of 10-8 M after 24h of treatment. In order to study estrogen receptor (ER) involvement, we evaluated the cellular localization and expression of ERs with immunofluorescence and western blot techniques after treatment with TCS and E2. Finally, through Real Time PCR analysis we have investigated gene expression of several molecular targets of estrogen pathway. We have observed that treatment with TCS and E2 induced an upregulation of Ki-67, cyclin D1 and cyclin E. We have also observed an upregulation of proinflammatory cytochines Il-1β after TCS and E2 treatment. These results confirm the estrogenic activity of TCS and suggest that estrogen and xenoestrogens may interfere with molecular pathways of prostate physiolog

Postural stability and plantar pressure parameters in healthy subjects: variability, correlation analysis and differences under open and closed eye conditions

Introduction: The “postural control system” acts through biomechanical strategies and functional neuromuscular adaptations to maintain body balance under static and dynamic conditions. Postural stability and body weight distribution can be affected by external sensory inputs, such as different visual stimuli. Little information is available about the influence of visual receptors on stabilometric and plantar pressure parameters. The aim of this study was to analyze variability, correlations, and changes in these parameters under open- (OE) and closed-eye (CE) conditions.Methods: A total of 31 stabilometric and plantar pressure parameters were acquired in 20 young and healthy adults during baropodometric examination performed in bipedal standing under both visual conditions. Variability of parameters was evaluated via the coefficient of variation, correlation analysis via Pearson’s R2, and statistical differences via the Wilcoxon test.Results: High intra-subject repeatability was found for all plantar pressure parameters and CoP-speed (CV < 40%) under OE and CE conditions, while CoP-sway area (CoPsa) and length surface function (LSF) showed larger variability (CV > 50%). Mean and peak pressures at midfoot and total foot loads showed the least number of significant correlations with other parameters under both visual conditions, whereas the arch-index and rearfoot loads showed the largest number of significant correlations. The limb side significantly affected most plantar pressure parameters. A trend of larger LSF and lower CoPsa and mean and peak pressures at the right forefoot was found under the CE condition.Discussion: The present study provides a deeper insight into the associations between postural stability and foot load. Interesting postural adaptations, particularly with respect to different visual stimuli, the effect of the dominant side, and the specific role of the midfoot in balance control were highlighted

Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype

Classical Rett syndrome (RTT) is a neurodevelopmental disorder where most of cases carry MECP2 mutations. Atypical RTT variants involve mutations in CDKL5 and FOXG1. However, a subset of RTT patients remains that do not carry any mutation in the described genes. Whole exome sequencing was carried out in a cohort of 21 female probands with clinical features overlapping with those of RTT, but without mutations in the customarily studied genes. Candidates were functionally validated by assessing the appearance of a neurological phenotype in Caenorhabditis elegans upon disruption of the corresponding ortholog gene. We detected pathogenic variants that accounted for the RTT-like phenotype in 14 (66.6 %) patients. Five patients were carriers of mutations in genes already known to be associated with other syndromic neurodevelopmental disorders. We determined that the other patients harbored mutations in genes that have not previously been linked to RTT or other neurodevelopmental syndromes, such as the ankyrin repeat containing protein ANKRD31 or the neuronal acetylcholine receptor subunit alpha-5 (CHRNA5). Furthermore, worm assays demonstrated that mutations in the studied candidate genes caused locomotion defects. Our findings indicate that mutations in a variety of genes contribute to the development of RTT-like phenotypes

Syntactic generation of practice novice programs in Python

Abstract: In the present day, computer programs are written in high level languages and parsed syntactically as part of a compilation process. These parsers are defined with context-free grammars (CFGs), a language recogniser for the respective programming language. Formal grammars in general are used for language recognition or generation. In this paper, we present the automatic generation of procedural programs in Python using a CFG. We have defined CFG rules to model program templates and implemented these rules to produce infinitely many distinct practice programs in Python. Each generated program is designed to test a novice programmer’s knowledge of functions, expressions, loops, and/or conditional statements. The CFG rules are highly generic and can be extended to generate programs in other procedural languages. The resulting programs can be used as practice, test or examination problems in introductory programming courses. 500,000 iterations of generated programs can be found at: https://tinyurl.com/ pythonprogramgenerator. A survey of 103 students’ perception showed that 93.1% strongly agreed that these programs can help them in practice and improve their programming skills